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The Graduates

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The Graduates is the talk show where we interview UC Berkeley graduates students about their work here on campus. Hosted by graduate students Ashley Smiley, Andrew Saintsing, and others, The Graduates airs every other Tu
Latest Episode9/15/2020

Sarah Guth

Andrew Saintsing: You'e tuned into 90.7 FM KALX Berkley. Im Andrew Saintsing. And this is TheGraduates, the interview talk show where we speak to UC Berkeley graduate studentsabout their work here on campus and around the world today, I'm joined by Sarah Guth,from the Department of Integrative Biology. Welcome to the show, Sarah.Sarah Guth: Thanks so much for having me. It's great to be here.Saintsing: It's great to have you here. You've been away for a while, right? And you just got backinto the country.Guth: Yeah, I was in Madagascar for eight months. I'm working with a team of researchers thatare studying bat-borne zoonoses.Saintsing: What did you say?Guth: Bat-borne zoonosis are diseases that are transmitted between animals and people likethe coronavirus that we're currently experiencing.Saintsing: You're not studying coronavirus though.Guth: I'm not specifically no, though the bats we study in Madagascar, do have betacoronaviruses we think, but we haven’t isolated them. So we don't know the exact,exact type of beta coronavirus. It's probably not COVID-19 but it may be somethingsimilar.Saintsing: So beta coronavirus, that's a, that's a big group of coronaviruses that there's a lot ofdifferences among beta coronaviruses?Guth: There is. Yeah. So there's four general groups of Coronaviruses. There’re the betacoronaviruses, the alpha coronaviruses, then I think delta and gamma. Um, I'm notexactly sure, but, uh, COVID-19 is a beta coronavirus. The beta and alpha coronavirusesare typically found in rodents and bats. So it's a large group of coronaviruses though. II've read that coronaviruses are very diverse, so you can have a very diverse set of betacoronaviruses in a particular bat species, which is part of the reason why they're sosusceptible to recombination and spilling over into not full hosts like humans.Saintsing: And that's just because there's so many different kinds of coronaviruses living in thesame bat that they can just get close to each other and share information.Guth: That's yeah. That's my understandingSaintsing: You're not really studying the coronaviruses though. Are you studying a particular virusthat the bats have?Guth: So, our group has historically looked at serological evidence of filoviruses andhenipaviruses. So...Saintsing: Serological evidence being blood?Guth: Yeah. Taking blood samples and looking for antibodies to look at past exposure tospecific pathogens or specific groups of pathogens, because oftentimes there can becross-reactivity between pathogens in our particular group. So you can't, we can't say,as of up to this point, we haven't been able to isolate specific pathogens in the bats, butwe know that there has been exposure to pathogens in the group known as filo viruses.So a Ebola is in the group of filoviruses. So yeah, my dissertation is not going to focusspecifically on Corona viruses, more focused on filo viruses and henipaviruses.Saintsing: What are henipaviruses?Guth: So henipaviruses, some examples you may have heard of. So Nipah virus is, and theseare not viruses that I've ever come to the US but Nipah spills over from bats to pigs, tohumans in Malaysia and from bats to humans in Bangladesh. And this happens quiteregularly in Bangladesh because, um, it's shed in bat urine and bats, well bat urine getsinto date palm sap and humans consume that sap. And so it happens actually annually.Saintsing: Like pretty bad or?Guth: Uh, yeah, it does. It is, um, the case fatality rate. I'm not sure exactly what it is, but it's,it's higher than COVID-19. I think it's almost as, or around as virulent as the SARSepidemic we saw in the early 2000s, but yeah, I'm not sure exactly what the case fatalityrate is.Saintsing: Is it, it's been known for a while, or like when was the first time they recorded cases of itin humans?Guth: Uh, it's a good question. I think it was in the late 19 hundreds was the first outbreak ofNipah. Um, but I, I don't remember exactly. I want to say the 1990s and the firstoutbreak was in Malaysia.Saintsing: Okay. And these are viruses that'll kind of burn out in human populations.Guth: The outbreaks are limited in human populations. Um, you'll have it's, it's not anythinglike we're seeing now with, uh, COVID-19. You need to have regular spillovers from thereservoir host, which is the bat, uh, to have any sort of prolonged epidemic.Saintsing: Right. But you're kind of less interested in the viruses themselves and more interested inlike how they're sustained in the bat populations and how they're moving through thatpopulation.Guth: So, I'm a, I'm a disease ecologist, which means that were interested in the dynamics ofdisease transmission as opposed to, I mean, sometimes so were, we often useepidemiological models and sometimes we do integrate information from the molecularlevel, but we're generally more focused on dynamics as opposed to understandingwhat's going on, on a within-host level, on a molecular level,Saintsing: Right. You look at, you look at a bunch of blood samples from a bunch of different batsto kind of see how widespread maybe these viruses have been in a bat population?Guth: We take blood samples from bats every month. Um, and we put the from threedifferent species, uh, and we put the blood samples in a centrifuge and we spin themdown. So you separate into a serum and a blood pellet, which has as, you know, thewipe, all the blood cells, uh, and then using that, we send that serum sample tocollaborators in Singapore, and they do, what's called a Luminex assay to, uh, look at theserology, to look at for serological evidence of exposure to henipaviruses, um, or if youlive viruses. And so then we know, you know, what bats have been exposed to thesepathogens. And what I'm interested in, one of my collaborators are interested in isfiguring out the average age at which an individual becomes first infected, because onceyou know that you can infer the rate of transmission within that population. So then youcan build what's called these, these age or prevalence models to then model thedynamics of transmission within that population.Saintsing: You want to know the average age at which the bat gets infected.Guth: Yeah. So we get the, and when we're looking at the age at which a bat becomesexposed, as we're looking at serology, um, so we get serology from blood samples andthen we get age. Um, what I'm currently working on now is trying to get age from, uh,DNA samples. So we take a piece of the wing tissue and we extract DNA. And we'retrying to look at the level of DNA methylation and correlate that with chronological age.So we can have this sort of epigenetic clock to determine the age of any bat. And there'sa group that is actually building this, this clock using wing tissue for other bat species.And we're going to try to apply their clock. But right now I'm trying to figure out the,essentially like the lab pipeline to get that done. Um, because it's not going to be easyto, to, to sequence, um, or to detect DNA methylation specific parts of the genomewithout spending tons of money.Saintsing: Okay. I gotta ask some questions about some of the things you just said. Okay. So DNAmethylation. So can you explain that just a little bit? Just like briefly.Guth: Yeah. Yeah. So I'm, I'm going to disclaimer, I'm pretty new to, um, Oh, this world ofgenomics. Um, and that's what I'm spending a lot of time doing, but yeah, so DNAmethylation is when, um, a methyl group is added to the, the DNA of the bat. Um, andpeople have found that the rate at which this happens is correlated with age. Um, andit's, it's a pretty new, um, this is a pretty new field. We don't know why, or whetherthere is a reason for this, like whether it plays there's evidence that may play a role inthe aging process, but we're not sure, but the point is that it's been shown across manydifferent species that you can. Um, so this often happens at, at what are called CPGsites. So it' just when you have a cytosine followed by a guanine. Um, and there arespecific sites that are, um, have levels of DNA methylation that are often correlated withchronological age. So you have to find those sites and then you measure the level ofDNA methylation at those sites and you can calculate age.Saintsing: Okay. So you, so there's DNA methylation. And you're saying, we don't really know likewhy it's happening. Um, but it is like shown to correlate well with age. Um, and then yousaid it was like CPG, those, the C's and the G's, those are like two examples of the basesyou can have for DNA. Um, and those are when C's when G's follow C's, those areparticularly susceptible to methylation.Guth: Yeah. Yeah. Sorry. I didn't explain that very clearly. Um, the methyl groups are added tothe site, are added to C and that opens happened where you have a C followed by a G,and DNA methylation is, um, I mean, it's epigenetic, so it's linked to gene expression,but there's this, um, there has been this other trend to kind of discover that it can be,we think it's involved in the aging process. We don't know exactly what the link is. Um,yeah, that's still being characterized.Saintsing: And you know, that often happens where C's are followed by G's, but you don't reallyknow like what the deal is. So is that just something like, that's a pattern you've seenand that's helpful because then you can know where if you sequence the genome, likeyou can like target those spaces to look for methylation. And that's like, why you carethat it's C's followed by G is not necessarily because there's anything, you know, likemechanistically that's happening when C's follow G's.Guth: Mostly we're using, um, this other group is, is building an epigenetic clock for bats. Um,and so they're picking out, they're focusing on these CPG sites because we know that,uh, you're more likely to find DNA methylation that's correlated with age at those sites.Um, and since we don't want to spend a lot of money, we're going to target that thesame sites that they identify. Um, so we're trying to figure out first how to take our, ourDNA genomes, how to, um, extract the, the CPG sites and then further extract the CPGsites that, um, that this other group have identified as being correlated withchronological age or biological age in bats.Saintsing: Right. And so that's why when you say chronologically - biological age, that's like, that'slike saying like some bats might develop different, like develop at different ratesbasically. Is that why you say biological age instead of chronological age?Guth: Yeah. So there is, there's been a lot of research in this field that, um, have looked atrates of aging as shown by DNA methylation versus rates like, you know, ourchronological age, which is what we, something that you might know before you look atthe DNA methylation age, um, and have found that in some species or in some, somediseases in humans even, um, will result in the acceleration of DNA methylation age orbiological age. And we think that since, like I said before, um, we think that DNAmethylation may play a role in aging because it is involved in gene expression. So youmay see some genes turned off as we age. Um, and so maybe, you know, having adisease, for example, like cancer may accelerate your, the, the, the stress on your DNA,the rate of aging biologically. Um, and so there is that people do make that, um, dodistinguish between biological and chronological age in this field.Guth: Um, but we&re, uh, our project is not going to make that distinction because we, we dohave, um, previously would be taking teeth from bats, uh, to get at their age. So if you,um, if you cut a tooth in half, um, you can actually count the rings. Yeah. So the bats putdown, um, they put down layers in their teeth annually kind of like a tree. So when youcut that tooth in half, you can count the rings and get their age. Um, but it's a really timeconsuming and stressful process for both the researchers and the bat. Um, more so forthe bat, obviously. Uh, and we only did it on a subset of adult bats. So, um, we're tryingto get away from that method. So we don' have chronological age for every bat. Um,and there also is quite a bit of variation in, or quite a bit of error in getting aged fromteeth. It's not a precise process. Um, so it wouldn't be fair to compare, um, or we don'tthink it would be fair to compare the DNA methylation, biological age with thechronological age.Saintsing: I see. Okay, you do all of this. You look at the DNA methylation, um, in your bloodsamples, just mostly to establish the ages of the bats that you've drawn blood from. Andthen you're also simultaneously looking for evidence of, uh, exposure to differentviruses. And so you want to compare to say like, okay, this bat is this old and it has beenexposed. So the earliest we can say that it was exposed was at this age.Guth: Yeah, exactly. So we're not gonna be able to say, you know, when in the history of thatbat has, has it been exposed, but across the entire data set, we can then identify, youknow, at what age do we see that bats start becoming exposed the average age at bats,we start becoming exposed. And then you can build these age seroprevalence modelswhere you can infer the transmission rate in the population and disease dynamics,Saintsing: The transmission rate. It's like,Guth: It's as simple as one divided by the average age at which a bat becomes infected is therate at which bats become infected. And then you can multiply that by the susceptibilityof the population and the infectiousness of the population and get a sense of what'scalled the force of infection. And that&#'s kind of our larger, it incorporates both the, therate of transmission and the contact rate between susceptibles and infectedSaintsing: And the susceptibility. What does that measure?Guth: So the susceptibility of the population is the proportion of individuals that aresusceptible. But so these age seroprevalence models don't take that into accountspecifically. It's yeah, it's, it's more dependent on that, that, um, one divided by theaverage age of infection.Saintsing: Right. And so that, that model is like what you're focused on. Like you're not reallyfocused on the force of infection. That's like something that will come after.Guth: It's a different way of calculating the force of infection, but they're just kind of generalthe point is that you can, um, yeah, the main point is I, by getting the average age ofinfection, dividing, you know, one dividing one, by that average age, you can get the,this transmission, you can get a sense of a transmission rate.Saintsing: You're looking at two different types of viruses, right? Like the filoviruses and what wasthe other type of virus?Guth: Henipaviruses.Saintsing: And so, are you, are you trying to like draw comparisons between these groups? Is thatwhy you have multiple?Guth: So just because we're, we're doing serological assets for those. And then also, um, the,we still don't really understand disease dynamics in bats. Um, that's have really, and youprobably read about this with COVID-19. Um, they have really remarkable immunesystems. Um, we don't really understand how, um, bats can sustain these infections intheir population. Um, you know, when, like I said, when Nipah spills over into people,it's a very limited outbreak because you don't have enough. There isn't enoughtransmission in the population because people that become infected aren't mobile andthey don't, they aren't able to infect new susceptible hosts. So yet we don't reallyunderstand how that's our sustaining these infections. So we build these epidemiologicmodels to get a better sense of what's going on. And so the goal is, you know, I meanthe more models you can build, maybe the easier it would be to get at the rules.Saintsing: Oh yeah. Like bats, they're so weird. Are there any, I mean, viruses that are actually, youknow, that actually have a negative impact on bats, it just seems like all of the virusesyou hear about like rabies, Ebola, coronavirus, Nipah, they all kind of just live in bats anddon't really affect them.Guth: So, rabies actually does have, um, that's can die from rabies and that's still, that's kind ofa complicated, we don't really know why. Um, but yeah, bats do have this crazy immunesystem. We think it's linked to the evolution of flight. Uh, so bats are the only flyingmammal. Um, and flight is a really metabolically expensive form of locomotion. So if youhave a human running at full speed, they raise their basal metabolic rate, maybe two tothree times, um, a rodent running might raise their basal metabolic rate seven times.Um, but a bat flying raises its metabolic rate 40 times. Um, so this is really metabolicallyexpensive. Uh, and with metabolism, we produce these what are called oxidative freeradicals, uh, and that can result in what's called the oxidative stress. So these oxidativefree radicals can, uh, can damage DNA. And we have cellular pathways for mitigatingthis damage, but at a certain point, the damage caused by metabolism can outrun thisability to mitigate the damage.Guth: Um, and that's what we know as aging. Um, so eventually, you know, your tissues andyour body can't keep up with this rate of DNA damage and, uh, things start to breakdown. Um, so bats, when you think for having such a high rate of metabolism, uh,wouldn't live as long as they're gonna, you know, you'd expect to have a really high rateof DNA damage. Um, and we see this with rodents, rodents have a higher metabolismthan many other mammals, and they don't live as long. Um, but bats live for a reallylong time. Um, so the longest lived bat is the brand that, and it lives up to 40 years inthe wild. And so what we think is happening is that bats have evolved these reallyefficient cellular pathways to mitigate the damage that they're causing to their DNA byflying. Um, and that these cellular pathways to mitigate DNA damage have also helpedthem sustain the damage that&';s caused by, um, viral infection, because a viral infectioncan also cause a similar amount of, um, damage that you see from metabolism, uh,because there's a lot of inflammation, so that are able to sustain a really high level ofinflammation.Guth: Um, because oftentimes like when we have a viral infection, our symptoms and thedamage that's caused for our body is often a result of our own immune response. So forexample, with COVID-19, um, you might've heard that patients that have a bad outcomehave this cytokine storm, um, that causes a lot of inflammation and cytokines are justthese, these signaling molecules that activate the immune system. And yeah, it causesthis really massive inflammatory response and bats and humans. We don't have theability to sustain that inflammation, but we think that that's are, are essentially primedto sustain that inflammation because they've been doing that for, to sustain theinflammation that's caused by flight.Saintsing: I got a couple questions for that. So the biological clocks that you make, I guess wouldn'tbe applicable to other animals, right. Because bats have unique rates of aging. And soyou kind of have to like really like tune it to bats.Guth: Yeah, yeah, exactly. Um, and I mean, biological clocks, these epigenetic clocks, peopleare making based on DNA. Methylation are very species specific regardless, but yeah,definitely. Um, we would not be able to look at compare, um, the DNA methylationlevels of bats with humans per se, and apply the same epigenetic clock.Saintsing: Right. And then, so with the cytokine storm, I guess I always just thought that like partof the problem was that you, you have so much acute inflammation, right. So, but thebats have inflammation. It's just that they keep it under control or like what, what doyou mean? They'e like primed for it? And they like sustain high levels of it.Guth: The papers I've read have generally said that they they're able to keep inflammation ornegative inflammation at a minimum. Um, and then they're able to use inflammationwhen they need it, um, when it's useful. Whereas, um, and people are humans, youknow, often will have it just like this massive inflammatory response that's completelyunrestricted and uncontrolled, whereas bats have a better ability to control it. So forexample, to get more into molecular details, I guess, that I'm not qualified to talk about,but, um, they have bats have this, uh, a constituent of interferon alpha, which is aspecific, it's a type of cytokine. Um, it's a signaling molecule that activates the immunesystem. Um, but it's really, really powerful. Um, so, in bats, it's, constituently expressed,so it's already there. It's ready to go. And when a virus comes in, it's able to activate amassive immune cascade.Guth: Um, but then the bats are able somehow able to manage that level of inflammation.Whereas, uh, I think so we don';t have, constituently expressed interferons. Um, we dohave interference in our immune system, but the&'re, they're activated, they're notalready there because if they were just already there, we would have way too muchinflammation and it would be how we'd have really negative outcomes. I have read that they use interferons in some cases in cancer treatments and it's a really, really brutaltreatment. Um, and they use it in very small doses, cause it is such a powerful, it doeselicit such a powerful response. And again, like bats are capable of withstanding that,but the human body is not.Saintsing: Okay. I see what you said. So basically the, the bats have all have like the signaling, um,information that we have. And so they, their immune system knows what's going on,but they have some capacity to just like, not go crazy with their response essentially. No,they just don't swell up. Like we would and all of that. And they don't have like reallyhigh fevers, I guess, that we would have.Guth: They, um, yeah. Another weird thing about that is they actually are able to withstandreally high temperatures. Um,Saintsing: I guess that makes sense because like they fly, so they like heat while they fly.Guth: So the flying actually kind of almost creates this fever response. Um, and there was ahypothesis, um, in the literature. I don't know if people are still considering this, butthey, people were saying that maybe that's one way of controlling these viral infectionsis that flying is like fever and that's how they keep replication down. Um, but the, theevolution of flight hypothesis seems to be more, um, more popular.Saintsing: It sounds like you're doing really interesting, cool stuff. What was it like being in aMadagascar for eight months?Guth: Yeah. And I really enjoyed it. We have a really great team of local researchers and thenthere is a few other American techs with me. It's definitely very different than Berkeley,but it was really cool. I really loved being in the field. Um, I had never done field workbefore this, um, are really held in animal at all. It was really cool. Yeah. It's good to beable to do everything and to collect data on the ground.Saintsing: Did you, like you stayed at a remote field station kind of, um, away from any biggercities or any or something like that?Guth: Um, so I actually lived in the capital and the biggest city and things like one between oneand 2 million people. Um, and I lived at the hospital, um, cause they have a lab there.Uh, so we would go into the field and collect biological samples and then bring oursamples back to the lab. Um, and the idea was to, uh, start doing DNA and RNAextractions in the lab, in the capital, um, and, but we had to leave because ofcoronavirus. So I was kinda in the middle of working on that.Saintsing: Oh, so you, you had the, the idea was to collect all of the samples and then start the,and start like extracting RNA and DNA after you had collected all of your samples.Guth: The idea was to, can I do it simultaneously. Um, but it took a while to figure out whatextraction kits to use and, and kind of get all the resources in country. Yeah. I'll probablygo back next January in between teaching to try to do some lab work.Saintsing: So do you think you'll be able to get it done in what a month or something like that?Guth: Um, maybe I don't know. We'll find out. Yeah. I'm not really sure. There, there is a reallygreat team of local researchers there. Uh, so we may, they may also get involved in thelab work, but yeah, we'll see, figure things out.Saintsing: A lot of, uh, figuring things out. I guess you came in with a plan, but it's been a lot of likeadapting to different circumstances, right?Guth: Yeah. Yeah. And that's, I mean, Madagascar is all about that. It's like you think, youknow, what's going to happen and then, you know, you spend three days trying to get toyour field site because the roads have been washed out, butSaintsing: I guess kind of like field science or even science in general. Right?Guth: Yeah, exactly.Saintsing: Yeah. So did you always know that you were going to be a scientist? Did you alwayswant to study science growing up?Guth: I did not know. Um, I didn't know that research could be a career. It was really a fielduntil I was a sophomore or junior in college. Um, I did a research experience forundergraduates internship, the REU internship, um, after my junior year. And they kindof trained you on what grad school was and how to apply. And that's why I decided togo to grad school. Um, cause I was really interested in science, but I thought if youstudied science, you had to become a high school biology teacher. And that was the onlyoption.Saintsing: Yeah. And the REU experiences, I guess, really good because it really motivated you topursue the research as a career.Guth: Yeah, that was definitely a life changing, internship and experience. Um, I realized that Ijust really loved research and collecting data. Um, I had a really hands off advisor. Um,and so I just kind of got to, like, he told me the title of the project and um, some data Icollect and I just kind of ran with it for the summer. Um, and you're also living veryclosely with, you know, 14 other interns from all over the world, all doing differentprojects. Um, and you just spend the summer, you know, all doing your researchprojects and hanging out and learning about different, um, disciplines. I actually did. Iwas in a, it was a, um, an engineering program. Um, so I was kind of the one out. It wasan environmental engineering. Uh, so it was all geared towards environmental science,which was, um, I was a joint biology and environmental science major. So that was apart of my work. But, uh, definitely I was like a little bit out of, um, a little bit out of mywheelhouse, but, uh, I just really enjoyed getting to know everybody and their differentfields. And then also leading, um, or playing such a big role in this project that myadvisor was doing.Saintsing: It looks like we'e running out of time on the interview. Do you, uh, have, uh, haveanything you'd like to leave the audience with?Guth: So, you know, these days everyone is obviously really focused on, um, COVID-19 it'shaving a huge impact on the world and, um, there's a lot of people buildingepidemiological models to make predictions about what's going to happen and youknow, what our requirements for, uh, PPE and what's going to be when the peak of theepidemic is going to happen. Um, and how many, what distribution of vaccines wewould need. Um, and there's a lot of different models coming out. Um, and I've my lab.And I have noticed that, um, the models that get the most attention are often themodels that have the sexy web interface that are easy to interact with. Um, so therewas a model, uh, that came out of a group in Washington. I think that, um, has beenkind of flooding social media. Um, that's essentially, it's just a statistical model fitting.Guth: Um, that predicts how many cases we'll see in different areas based on, uh, theepidemic curves we've seen in completely different parts of the world. Um, and I think Iwould just caution people to, when you see models like this, not take it at face valueand try to look under the hood and see what the, what the methods are, how are theybuilding the model? You know, is it statistic is a statistical model? Is it a mechanisticmodel? If it's a mechanistic model, how are they estimating the transmission rate?Because there's a really, really wide estimate, um, or range for, uh, estimates oftransmission rate. And that has a huge impact on the predictions because it can be, uh,uh, it can be confusing to kind of weed through all these models that are coming outand figure out what predictions will actually be. So, yeah, I think just being careful aboutreposting models that you see published and, you know, not just taking that at facevalue, thinking a little bit more critically about what the information you're seeing isbuilt on.Saintsing: Yeah. Okay. Um, that's like a really good point. And you know, even not just in, uh, timesof COVID-19, but also in understanding science in general, right. It's really important.Today I've been speaking with Sarah Guth from the Department of Integrative Biology.Thank you so much for being on the show, Sarah.Guth: Yeah, thanks for having me.Saintsing: So great to have you.
9/15/2020

Sarah Guth

Andrew Saintsing: You'e tuned into 90.7 FM KALX Berkley. Im Andrew Saintsing. And this is TheGraduates, the interview talk show where we speak to UC Berkeley graduate studentsabout their work here on campus and around the world today, I'm joined by Sarah Guth,from the Department of Integrative Biology. Welcome to the show, Sarah.Sarah Guth: Thanks so much for having me. It's great to be here.Saintsing: It's great to have you here. You've been away for a while, right? And you just got backinto the country.Guth: Yeah, I was in Madagascar for eight months. I'm working with a team of researchers thatare studying bat-borne zoonoses.Saintsing: What did you say?Guth: Bat-borne zoonosis are diseases that are transmitted between animals and people likethe coronavirus that we're currently experiencing.Saintsing: You're not studying coronavirus though.Guth: I'm not specifically no, though the bats we study in Madagascar, do have betacoronaviruses we think, but we haven’t isolated them. So we don't know the exact,exact type of beta coronavirus. It's probably not COVID-19 but it may be somethingsimilar.Saintsing: So beta coronavirus, that's a, that's a big group of coronaviruses that there's a lot ofdifferences among beta coronaviruses?Guth: There is. Yeah. So there's four general groups of Coronaviruses. There’re the betacoronaviruses, the alpha coronaviruses, then I think delta and gamma. Um, I'm notexactly sure, but, uh, COVID-19 is a beta coronavirus. The beta and alpha coronavirusesare typically found in rodents and bats. So it's a large group of coronaviruses though. II've read that coronaviruses are very diverse, so you can have a very diverse set of betacoronaviruses in a particular bat species, which is part of the reason why they're sosusceptible to recombination and spilling over into not full hosts like humans.Saintsing: And that's just because there's so many different kinds of coronaviruses living in thesame bat that they can just get close to each other and share information.Guth: That's yeah. That's my understandingSaintsing: You're not really studying the coronaviruses though. Are you studying a particular virusthat the bats have?Guth: So, our group has historically looked at serological evidence of filoviruses andhenipaviruses. So...Saintsing: Serological evidence being blood?Guth: Yeah. Taking blood samples and looking for antibodies to look at past exposure tospecific pathogens or specific groups of pathogens, because oftentimes there can becross-reactivity between pathogens in our particular group. So you can't, we can't say,as of up to this point, we haven't been able to isolate specific pathogens in the bats, butwe know that there has been exposure to pathogens in the group known as filo viruses.So a Ebola is in the group of filoviruses. So yeah, my dissertation is not going to focusspecifically on Corona viruses, more focused on filo viruses and henipaviruses.Saintsing: What are henipaviruses?Guth: So henipaviruses, some examples you may have heard of. So Nipah virus is, and theseare not viruses that I've ever come to the US but Nipah spills over from bats to pigs, tohumans in Malaysia and from bats to humans in Bangladesh. And this happens quiteregularly in Bangladesh because, um, it's shed in bat urine and bats, well bat urine getsinto date palm sap and humans consume that sap. And so it happens actually annually.Saintsing: Like pretty bad or?Guth: Uh, yeah, it does. It is, um, the case fatality rate. I'm not sure exactly what it is, but it's,it's higher than COVID-19. I think it's almost as, or around as virulent as the SARSepidemic we saw in the early 2000s, but yeah, I'm not sure exactly what the case fatalityrate is.Saintsing: Is it, it's been known for a while, or like when was the first time they recorded cases of itin humans?Guth: Uh, it's a good question. I think it was in the late 19 hundreds was the first outbreak ofNipah. Um, but I, I don't remember exactly. I want to say the 1990s and the firstoutbreak was in Malaysia.Saintsing: Okay. And these are viruses that'll kind of burn out in human populations.Guth: The outbreaks are limited in human populations. Um, you'll have it's, it's not anythinglike we're seeing now with, uh, COVID-19. You need to have regular spillovers from thereservoir host, which is the bat, uh, to have any sort of prolonged epidemic.Saintsing: Right. But you're kind of less interested in the viruses themselves and more interested inlike how they're sustained in the bat populations and how they're moving through thatpopulation.Guth: So, I'm a, I'm a disease ecologist, which means that were interested in the dynamics ofdisease transmission as opposed to, I mean, sometimes so were, we often useepidemiological models and sometimes we do integrate information from the molecularlevel, but we're generally more focused on dynamics as opposed to understandingwhat's going on, on a within-host level, on a molecular level,Saintsing: Right. You look at, you look at a bunch of blood samples from a bunch of different batsto kind of see how widespread maybe these viruses have been in a bat population?Guth: We take blood samples from bats every month. Um, and we put the from threedifferent species, uh, and we put the blood samples in a centrifuge and we spin themdown. So you separate into a serum and a blood pellet, which has as, you know, thewipe, all the blood cells, uh, and then using that, we send that serum sample tocollaborators in Singapore, and they do, what's called a Luminex assay to, uh, look at theserology, to look at for serological evidence of exposure to henipaviruses, um, or if youlive viruses. And so then we know, you know, what bats have been exposed to thesepathogens. And what I'm interested in, one of my collaborators are interested in isfiguring out the average age at which an individual becomes first infected, because onceyou know that you can infer the rate of transmission within that population. So then youcan build what's called these, these age or prevalence models to then model thedynamics of transmission within that population.Saintsing: You want to know the average age at which the bat gets infected.Guth: Yeah. So we get the, and when we're looking at the age at which a bat becomesexposed, as we're looking at serology, um, so we get serology from blood samples andthen we get age. Um, what I'm currently working on now is trying to get age from, uh,DNA samples. So we take a piece of the wing tissue and we extract DNA. And we'retrying to look at the level of DNA methylation and correlate that with chronological age.So we can have this sort of epigenetic clock to determine the age of any bat. And there'sa group that is actually building this, this clock using wing tissue for other bat species.And we're going to try to apply their clock. But right now I'm trying to figure out the,essentially like the lab pipeline to get that done. Um, because it's not going to be easyto, to, to sequence, um, or to detect DNA methylation specific parts of the genomewithout spending tons of money.Saintsing: Okay. I gotta ask some questions about some of the things you just said. Okay. So DNAmethylation. So can you explain that just a little bit? Just like briefly.Guth: Yeah. Yeah. So I'm, I'm going to disclaimer, I'm pretty new to, um, Oh, this world ofgenomics. Um, and that's what I'm spending a lot of time doing, but yeah, so DNAmethylation is when, um, a methyl group is added to the, the DNA of the bat. Um, andpeople have found that the rate at which this happens is correlated with age. Um, andit's, it's a pretty new, um, this is a pretty new field. We don't know why, or whetherthere is a reason for this, like whether it plays there's evidence that may play a role inthe aging process, but we're not sure, but the point is that it's been shown across manydifferent species that you can. Um, so this often happens at, at what are called CPGsites. So it' just when you have a cytosine followed by a guanine. Um, and there arespecific sites that are, um, have levels of DNA methylation that are often correlated withchronological age. So you have to find those sites and then you measure the level ofDNA methylation at those sites and you can calculate age.Saintsing: Okay. So you, so there's DNA methylation. And you're saying, we don't really know likewhy it's happening. Um, but it is like shown to correlate well with age. Um, and then yousaid it was like CPG, those, the C's and the G's, those are like two examples of the basesyou can have for DNA. Um, and those are when C's when G's follow C's, those areparticularly susceptible to methylation.Guth: Yeah. Yeah. Sorry. I didn't explain that very clearly. Um, the methyl groups are added tothe site, are added to C and that opens happened where you have a C followed by a G,and DNA methylation is, um, I mean, it's epigenetic, so it's linked to gene expression,but there's this, um, there has been this other trend to kind of discover that it can be,we think it's involved in the aging process. We don't know exactly what the link is. Um,yeah, that's still being characterized.Saintsing: And you know, that often happens where C's are followed by G's, but you don't reallyknow like what the deal is. So is that just something like, that's a pattern you've seenand that's helpful because then you can know where if you sequence the genome, likeyou can like target those spaces to look for methylation. And that's like, why you carethat it's C's followed by G is not necessarily because there's anything, you know, likemechanistically that's happening when C's follow G's.Guth: Mostly we're using, um, this other group is, is building an epigenetic clock for bats. Um,and so they're picking out, they're focusing on these CPG sites because we know that,uh, you're more likely to find DNA methylation that's correlated with age at those sites.Um, and since we don't want to spend a lot of money, we're going to target that thesame sites that they identify. Um, so we're trying to figure out first how to take our, ourDNA genomes, how to, um, extract the, the CPG sites and then further extract the CPGsites that, um, that this other group have identified as being correlated withchronological age or biological age in bats.Saintsing: Right. And so that's why when you say chronologically - biological age, that's like, that'slike saying like some bats might develop different, like develop at different ratesbasically. Is that why you say biological age instead of chronological age?Guth: Yeah. So there is, there's been a lot of research in this field that, um, have looked atrates of aging as shown by DNA methylation versus rates like, you know, ourchronological age, which is what we, something that you might know before you look atthe DNA methylation age, um, and have found that in some species or in some, somediseases in humans even, um, will result in the acceleration of DNA methylation age orbiological age. And we think that since, like I said before, um, we think that DNAmethylation may play a role in aging because it is involved in gene expression. So youmay see some genes turned off as we age. Um, and so maybe, you know, having adisease, for example, like cancer may accelerate your, the, the, the stress on your DNA,the rate of aging biologically. Um, and so there is that people do make that, um, dodistinguish between biological and chronological age in this field.Guth: Um, but we&re, uh, our project is not going to make that distinction because we, we dohave, um, previously would be taking teeth from bats, uh, to get at their age. So if you,um, if you cut a tooth in half, um, you can actually count the rings. Yeah. So the bats putdown, um, they put down layers in their teeth annually kind of like a tree. So when youcut that tooth in half, you can count the rings and get their age. Um, but it's a really timeconsuming and stressful process for both the researchers and the bat. Um, more so forthe bat, obviously. Uh, and we only did it on a subset of adult bats. So, um, we're tryingto get away from that method. So we don' have chronological age for every bat. Um,and there also is quite a bit of variation in, or quite a bit of error in getting aged fromteeth. It's not a precise process. Um, so it wouldn't be fair to compare, um, or we don'tthink it would be fair to compare the DNA methylation, biological age with thechronological age.Saintsing: I see. Okay, you do all of this. You look at the DNA methylation, um, in your bloodsamples, just mostly to establish the ages of the bats that you've drawn blood from. Andthen you're also simultaneously looking for evidence of, uh, exposure to differentviruses. And so you want to compare to say like, okay, this bat is this old and it has beenexposed. So the earliest we can say that it was exposed was at this age.Guth: Yeah, exactly. So we're not gonna be able to say, you know, when in the history of thatbat has, has it been exposed, but across the entire data set, we can then identify, youknow, at what age do we see that bats start becoming exposed the average age at bats,we start becoming exposed. And then you can build these age seroprevalence modelswhere you can infer the transmission rate in the population and disease dynamics,Saintsing: The transmission rate. It's like,Guth: It's as simple as one divided by the average age at which a bat becomes infected is therate at which bats become infected. And then you can multiply that by the susceptibilityof the population and the infectiousness of the population and get a sense of what'scalled the force of infection. And that&#'s kind of our larger, it incorporates both the, therate of transmission and the contact rate between susceptibles and infectedSaintsing: And the susceptibility. What does that measure?Guth: So the susceptibility of the population is the proportion of individuals that aresusceptible. But so these age seroprevalence models don't take that into accountspecifically. It's yeah, it's, it's more dependent on that, that, um, one divided by theaverage age of infection.Saintsing: Right. And so that, that model is like what you're focused on. Like you're not reallyfocused on the force of infection. That's like something that will come after.Guth: It's a different way of calculating the force of infection, but they're just kind of generalthe point is that you can, um, yeah, the main point is I, by getting the average age ofinfection, dividing, you know, one dividing one, by that average age, you can get the,this transmission, you can get a sense of a transmission rate.Saintsing: You're looking at two different types of viruses, right? Like the filoviruses and what wasthe other type of virus?Guth: Henipaviruses.Saintsing: And so, are you, are you trying to like draw comparisons between these groups? Is thatwhy you have multiple?Guth: So just because we're, we're doing serological assets for those. And then also, um, the,we still don't really understand disease dynamics in bats. Um, that's have really, and youprobably read about this with COVID-19. Um, they have really remarkable immunesystems. Um, we don't really understand how, um, bats can sustain these infections intheir population. Um, you know, when, like I said, when Nipah spills over into people,it's a very limited outbreak because you don't have enough. There isn't enoughtransmission in the population because people that become infected aren't mobile andthey don't, they aren't able to infect new susceptible hosts. So yet we don't reallyunderstand how that's our sustaining these infections. So we build these epidemiologicmodels to get a better sense of what's going on. And so the goal is, you know, I meanthe more models you can build, maybe the easier it would be to get at the rules.Saintsing: Oh yeah. Like bats, they're so weird. Are there any, I mean, viruses that are actually, youknow, that actually have a negative impact on bats, it just seems like all of the virusesyou hear about like rabies, Ebola, coronavirus, Nipah, they all kind of just live in bats anddon't really affect them.Guth: So, rabies actually does have, um, that's can die from rabies and that's still, that's kind ofa complicated, we don't really know why. Um, but yeah, bats do have this crazy immunesystem. We think it's linked to the evolution of flight. Uh, so bats are the only flyingmammal. Um, and flight is a really metabolically expensive form of locomotion. So if youhave a human running at full speed, they raise their basal metabolic rate, maybe two tothree times, um, a rodent running might raise their basal metabolic rate seven times.Um, but a bat flying raises its metabolic rate 40 times. Um, so this is really metabolicallyexpensive. Uh, and with metabolism, we produce these what are called oxidative freeradicals, uh, and that can result in what's called the oxidative stress. So these oxidativefree radicals can, uh, can damage DNA. And we have cellular pathways for mitigatingthis damage, but at a certain point, the damage caused by metabolism can outrun thisability to mitigate the damage.Guth: Um, and that's what we know as aging. Um, so eventually, you know, your tissues andyour body can't keep up with this rate of DNA damage and, uh, things start to breakdown. Um, so bats, when you think for having such a high rate of metabolism, uh,wouldn't live as long as they're gonna, you know, you'd expect to have a really high rateof DNA damage. Um, and we see this with rodents, rodents have a higher metabolismthan many other mammals, and they don't live as long. Um, but bats live for a reallylong time. Um, so the longest lived bat is the brand that, and it lives up to 40 years inthe wild. And so what we think is happening is that bats have evolved these reallyefficient cellular pathways to mitigate the damage that they're causing to their DNA byflying. Um, and that these cellular pathways to mitigate DNA damage have also helpedthem sustain the damage that&';s caused by, um, viral infection, because a viral infectioncan also cause a similar amount of, um, damage that you see from metabolism, uh,because there's a lot of inflammation, so that are able to sustain a really high level ofinflammation.Guth: Um, because oftentimes like when we have a viral infection, our symptoms and thedamage that's caused for our body is often a result of our own immune response. So forexample, with COVID-19, um, you might've heard that patients that have a bad outcomehave this cytokine storm, um, that causes a lot of inflammation and cytokines are justthese, these signaling molecules that activate the immune system. And yeah, it causesthis really massive inflammatory response and bats and humans. We don't have theability to sustain that inflammation, but we think that that's are, are essentially primedto sustain that inflammation because they've been doing that for, to sustain theinflammation that's caused by flight.Saintsing: I got a couple questions for that. So the biological clocks that you make, I guess wouldn'tbe applicable to other animals, right. Because bats have unique rates of aging. And soyou kind of have to like really like tune it to bats.Guth: Yeah, yeah, exactly. Um, and I mean, biological clocks, these epigenetic clocks, peopleare making based on DNA. Methylation are very species specific regardless, but yeah,definitely. Um, we would not be able to look at compare, um, the DNA methylationlevels of bats with humans per se, and apply the same epigenetic clock.Saintsing: Right. And then, so with the cytokine storm, I guess I always just thought that like partof the problem was that you, you have so much acute inflammation, right. So, but thebats have inflammation. It's just that they keep it under control or like what, what doyou mean? They'e like primed for it? And they like sustain high levels of it.Guth: The papers I've read have generally said that they they're able to keep inflammation ornegative inflammation at a minimum. Um, and then they're able to use inflammationwhen they need it, um, when it's useful. Whereas, um, and people are humans, youknow, often will have it just like this massive inflammatory response that's completelyunrestricted and uncontrolled, whereas bats have a better ability to control it. So forexample, to get more into molecular details, I guess, that I'm not qualified to talk about,but, um, they have bats have this, uh, a constituent of interferon alpha, which is aspecific, it's a type of cytokine. Um, it's a signaling molecule that activates the immunesystem. Um, but it's really, really powerful. Um, so, in bats, it's, constituently expressed,so it's already there. It's ready to go. And when a virus comes in, it's able to activate amassive immune cascade.Guth: Um, but then the bats are able somehow able to manage that level of inflammation.Whereas, uh, I think so we don';t have, constituently expressed interferons. Um, we dohave interference in our immune system, but the&'re, they're activated, they're notalready there because if they were just already there, we would have way too muchinflammation and it would be how we'd have really negative outcomes. I have read that they use interferons in some cases in cancer treatments and it's a really, really brutaltreatment. Um, and they use it in very small doses, cause it is such a powerful, it doeselicit such a powerful response. And again, like bats are capable of withstanding that,but the human body is not.Saintsing: Okay. I see what you said. So basically the, the bats have all have like the signaling, um,information that we have. And so they, their immune system knows what's going on,but they have some capacity to just like, not go crazy with their response essentially. No,they just don't swell up. Like we would and all of that. And they don't have like reallyhigh fevers, I guess, that we would have.Guth: They, um, yeah. Another weird thing about that is they actually are able to withstandreally high temperatures. Um,Saintsing: I guess that makes sense because like they fly, so they like heat while they fly.Guth: So the flying actually kind of almost creates this fever response. Um, and there was ahypothesis, um, in the literature. I don't know if people are still considering this, butthey, people were saying that maybe that's one way of controlling these viral infectionsis that flying is like fever and that's how they keep replication down. Um, but the, theevolution of flight hypothesis seems to be more, um, more popular.Saintsing: It sounds like you're doing really interesting, cool stuff. What was it like being in aMadagascar for eight months?Guth: Yeah. And I really enjoyed it. We have a really great team of local researchers and thenthere is a few other American techs with me. It's definitely very different than Berkeley,but it was really cool. I really loved being in the field. Um, I had never done field workbefore this, um, are really held in animal at all. It was really cool. Yeah. It's good to beable to do everything and to collect data on the ground.Saintsing: Did you, like you stayed at a remote field station kind of, um, away from any biggercities or any or something like that?Guth: Um, so I actually lived in the capital and the biggest city and things like one between oneand 2 million people. Um, and I lived at the hospital, um, cause they have a lab there.Uh, so we would go into the field and collect biological samples and then bring oursamples back to the lab. Um, and the idea was to, uh, start doing DNA and RNAextractions in the lab, in the capital, um, and, but we had to leave because ofcoronavirus. So I was kinda in the middle of working on that.Saintsing: Oh, so you, you had the, the idea was to collect all of the samples and then start the,and start like extracting RNA and DNA after you had collected all of your samples.Guth: The idea was to, can I do it simultaneously. Um, but it took a while to figure out whatextraction kits to use and, and kind of get all the resources in country. Yeah. I'll probablygo back next January in between teaching to try to do some lab work.Saintsing: So do you think you'll be able to get it done in what a month or something like that?Guth: Um, maybe I don't know. We'll find out. Yeah. I'm not really sure. There, there is a reallygreat team of local researchers there. Uh, so we may, they may also get involved in thelab work, but yeah, we'll see, figure things out.Saintsing: A lot of, uh, figuring things out. I guess you came in with a plan, but it's been a lot of likeadapting to different circumstances, right?Guth: Yeah. Yeah. And that's, I mean, Madagascar is all about that. It's like you think, youknow, what's going to happen and then, you know, you spend three days trying to get toyour field site because the roads have been washed out, butSaintsing: I guess kind of like field science or even science in general. Right?Guth: Yeah, exactly.Saintsing: Yeah. So did you always know that you were going to be a scientist? Did you alwayswant to study science growing up?Guth: I did not know. Um, I didn't know that research could be a career. It was really a fielduntil I was a sophomore or junior in college. Um, I did a research experience forundergraduates internship, the REU internship, um, after my junior year. And they kindof trained you on what grad school was and how to apply. And that's why I decided togo to grad school. Um, cause I was really interested in science, but I thought if youstudied science, you had to become a high school biology teacher. And that was the onlyoption.Saintsing: Yeah. And the REU experiences, I guess, really good because it really motivated you topursue the research as a career.Guth: Yeah, that was definitely a life changing, internship and experience. Um, I realized that Ijust really loved research and collecting data. Um, I had a really hands off advisor. Um,and so I just kind of got to, like, he told me the title of the project and um, some data Icollect and I just kind of ran with it for the summer. Um, and you're also living veryclosely with, you know, 14 other interns from all over the world, all doing differentprojects. Um, and you just spend the summer, you know, all doing your researchprojects and hanging out and learning about different, um, disciplines. I actually did. Iwas in a, it was a, um, an engineering program. Um, so I was kind of the one out. It wasan environmental engineering. Uh, so it was all geared towards environmental science,which was, um, I was a joint biology and environmental science major. So that was apart of my work. But, uh, definitely I was like a little bit out of, um, a little bit out of mywheelhouse, but, uh, I just really enjoyed getting to know everybody and their differentfields. And then also leading, um, or playing such a big role in this project that myadvisor was doing.Saintsing: It looks like we'e running out of time on the interview. Do you, uh, have, uh, haveanything you'd like to leave the audience with?Guth: So, you know, these days everyone is obviously really focused on, um, COVID-19 it'shaving a huge impact on the world and, um, there's a lot of people buildingepidemiological models to make predictions about what's going to happen and youknow, what our requirements for, uh, PPE and what's going to be when the peak of theepidemic is going to happen. Um, and how many, what distribution of vaccines wewould need. Um, and there's a lot of different models coming out. Um, and I've my lab.And I have noticed that, um, the models that get the most attention are often themodels that have the sexy web interface that are easy to interact with. Um, so therewas a model, uh, that came out of a group in Washington. I think that, um, has beenkind of flooding social media. Um, that's essentially, it's just a statistical model fitting.Guth: Um, that predicts how many cases we'll see in different areas based on, uh, theepidemic curves we've seen in completely different parts of the world. Um, and I think Iwould just caution people to, when you see models like this, not take it at face valueand try to look under the hood and see what the, what the methods are, how are theybuilding the model? You know, is it statistic is a statistical model? Is it a mechanisticmodel? If it's a mechanistic model, how are they estimating the transmission rate?Because there's a really, really wide estimate, um, or range for, uh, estimates oftransmission rate. And that has a huge impact on the predictions because it can be, uh,uh, it can be confusing to kind of weed through all these models that are coming outand figure out what predictions will actually be. So, yeah, I think just being careful aboutreposting models that you see published and, you know, not just taking that at facevalue, thinking a little bit more critically about what the information you're seeing isbuilt on.Saintsing: Yeah. Okay. Um, that's like a really good point. And you know, even not just in, uh, timesof COVID-19, but also in understanding science in general, right. It's really important.Today I've been speaking with Sarah Guth from the Department of Integrative Biology.Thank you so much for being on the show, Sarah.Guth: Yeah, thanks for having me.Saintsing: So great to have you.
9/1/2020

Kwasi Wrensford

Mattina Alonge: Hello. Hello, you're listening to 90.7 KALX Berkeley. I'm Mattina, and this is The Graduates an interview style show where we get a glimpse into the work and experiences of UC Berkeley graduate students. Today, I'm sitting here with Kwasi Wrensford, a PhD student in the Department of Integrative Biology. Welcome, Kwasi.Kwasi Wrensford: Hi, Mattina, thanks for having me.Alonge: You describe yourself as a behavioral ecologist. And I'm wondering if you can explain a little about what that actually means,Wrensford: Right. Uh, that's a great question. So a behavioral ecologists, we sort of describe ourselves. So we focus on animal behavior kind of, um, as the big general guiding principle, but what kind of makes it behavioral ecology is we're interested in animal behavior in the larger context of an animal's environment and its interactions with, with that environment and with other animals in the environment. So a lot of behavioral ecologists, um, tend to focus a lot on things like mating behavior, um, how they find and acquire food and how they might compete with other species or with, um, individuals within their own species. So that's kind of a short version of what's a behavioral ecologist is.Alonge: Okay. Basically how an animal interacts with both living and nonliving aspects of this world. Yeah. Um, is there one of those things that's more important?Wrensford: That's, that's a really good question. Um, and I guess personally, I don't know if I could make an argument for one or the other. I think it's all integrated, you know, I think these aren't mutually exclusive things, right. So one drives the other, drives the other, right. So, uh, it just kind of often depends on what people are more interested in or what they kind of what their little favorite aspect of animal behavior is. Um, but me personally, I don't think they're, um, one's more important than the other.Alonge: Okay. On that topic. What got you really excited about animal behavior?Wrensford: Yeah. So I've always loved animals. I was kind of the, I was always the weird kid who was always into, uh, into animal books and I loved going to the zoo. And so I always liked animals just in general, but I guess what got me interested in animal behavior is like an actual research topic was, uh, actually in my undergraduate years, I got a, I got a special grant or scholarship through the National Science Foundation that they give to undergraduate students to go out and do a research project with a lab somewhere in the country. And so I got a grant to go out to this amazing field station in Colorado, the Rocky Mountain Biological Lab. And there, I got to work with, uh, a professor Daniel Blumstein who studied the behavior of these awesome animals, yellow-bellied marmots, they're very cute. Um, you know, if you've ever seen, like if you ever been out into the mountains of California, they're up there, or if you're back East, woodchucks are very similar, groundhogs.Wrensford: Just very large fat squirrels. But this project is really cool because it was like a, it's a long-term study. So they've been studying the same population of marmots for the past, uh, since the sixties. Um, yeah. So my old advisor, Dan, Dan, he was actually the second PI to head this project. And so yeah, I got to go out there, trap the marmots, observe them and sort of work on all aspects of the project. And that really is what got me thinking that, and, you know, behavioral research is a thing that I could actually do, you know, actually just kind of watch animals in their own environment and start with, from my science, from there, you know, that's a really cool feeling. There's immense value in, um, captive laboratory animal research. And, you know, we've learned so much from the models we have, but you know, you can't replace actually, I'm seeing an animal in its natural habitat when you're asking like evolutionary or ecological questions. Right. Because that's where, that's where they are. That's where the what's out there. Yeah.Alonge: Yeah. On the other hand, it seems that that could be somewhat challenging in a lot of ways. What particular things do you find challenging when studying animal behavior, animal ecology?Wrensford: Yeah. So you're definitely correct. It's a, it's very challenging. It's a very difficult way to do work. You know, like, you know, the, we talk about the benefits and that you can get these, uh, observations and insights into animals in their natural habitat. But the main benefit of doing lab work right, is you have ultimate control. You know, if you want to know one specific aspect of an animal's biology in a lab setting, you can manipulate any little piece that you need to, to isolate the effect that you're interested in, but in the field you can't do that, right. The animals are going about living their lives and you just kind of have to roll with it and you get, you get what you get basically. And you're at the mercy of nature, you're at the mercy of the animals. And, you know, sometimes, and sometimes that leads to really great moments. Like I know there's a lot of stories of people doing research in nature, just kind of handed them the perfect experiment, either like a storm shakes things up in just the right way. But a lot of times it just ends up being a lot of headaches and a lot of improvising once you're out there.Alonge: Do you have any specific stories of things that were particularly frustrating from your work either then in Colorado or as a graduate student here?Wrensford: Um, I have plenty. I guess, kind of the most immediate story. So my current work, uh, I work in the Sierra Nevada in California. I work with chipmunks, uh, right outside of Yosemite and kind of one of the biggest troubles in the last year is just the, uh, is the, with the heavy snows over the winter, the snow melted a lot later than the previous year. So, and with the, snow's not melted yet a lot of the roads that high up don't open. And so I'm in a lot of ways, I'm just at the mercy of, of precipitation and, uh, to, I can actually get out and see my animals. And so remember last, uh, last year I was just kind of had the, um, weather service kind of snow pack measure and was refreshing it over and over again. Um, in like late June, early July, just waiting for the roads I needed to open up. And that's just like the tip of the iceberg, you know, I haven't even gotten out there yet and it's already, I'm already at the winds of nature.Alonge: Right. So you're studying chipmunks. Now, you said, um, are these the same chipmunks that we might see in our backyards or is there something special about the chipmunks?Wrensford: Right. So the chipmunk species I study now are two species that are basically exclusive to the Sierra, Nevada, California. Um, one of the kind of quirky things about chipmunks is that in the Western, in Western North America, they're actually incredibly diverse. So we have about 20 to 30 chipmunk species. So we have one species for the entirety of Eurasia, the Siberian chipmunk. We have one species for the entirety of Eastern North America, the Eastern chipmunk, and then all the other 20 something myriad species are in the Western, in Western North America.Alonge: So why, how did that happen?Wrensford: Myriad of reasons we think because Western North America is much more mountainous and a lot more complex terrain that in the last, uh, glacial periods, uh, these populations were much more isolated and diversifying in isolation. And then once the glaciers receded, they came back into contact, but by then they had already diversified and reproductively isolated themselves. So that's kind of the prevailing theory, you know, there's a lot of caveats to that. Um, but yeah, that's kind of the driving story that we think is why these Western chipmunk species are so diverse.Alonge: Got it. Yeah.Wrensford: So the species that I study are the alpine chipmunk and the lodgepole chipmunk, and kind of what makes them interesting is that they both kind of live at the sort of the top elevational range that you will find chipmunks in the mountains there. So you can find both of these species between about nine to 11,000 feet high, so they they're really high up there. So, and that's pretty high for humans too. That's about, that's about the range where humans start suffering really severe altitude sickness. So you can, so we can imagine these animals are pretty well well adapted to their environments to be able to survive and thrive up there. But what's curious about them is that I work in a Museum of Vertebrate Zoology and at UC Berkeley, one of the benefits of working in a museum is that you have a really rich datasets going back in history. And one of the datasets that we have is actually that we took some of the old field notes from the curators of the museum back in the early 20th century when the museum first started, um, when they were doing surveys of, uh, mammals throughout California. And we're able to take these really detailed field notes and redo the same surveys along the same areas and same locations that they did that gives us a really good idea how those communities have changed over the past hundred years.Wrensford: And with that data, we've seen that through combination of climate change and human intervention and land use change that animals are responding very, very, um, acutely to these changes, but not consistently. So there's differences in variation in how these animals are responding. So some animals seem to be their range of seem to be shrinking, especially a lot of high elevation specialists as temperatures get warmer, they're moving further up the mountain to track temperatures, but then you have some species that live in similar habitats that don't seem to be showing much change at all in their range. And that brings us to our chipmunks, that these two species that live in the similar habitat, my lodgepole chipmunks, their range hasn't changed at all, almost in the past 100 years, while the alpine chipmunk, it's been moving further up slope in elevation to track those changes in temperatures. And so that's kind of sets up in really neat little natural comparison. What's different about these two species or one seems to be more acutely reacting to these changes in habitat than the other.Alonge: Yeah and is there a particular way that humans are cultural influences shifting their habitat or pressuring them to shift their habitat?Wrensford: No, that's a really good point. So I think the main culprit for what's really shifting their habitat and kind of with the resurvey project and a lot of people working on it, we think it's broad climate change. So we think mostly this broad increase in temperature over the past century postindustrial, um, is what's really driving these changes. And we can see that in, in the actual kind of weather and temperature measurements that we're seeing localities average mean temperature is going up, but it's a broader story than temperature too. There's all sorts of interacting and synergistic effects, not just, um, it's getting warmer, right? So the warmer temperatures make are making the snow melts earlier. They're decreasing snowpack in the winter and all sorts of other effects that are interacting with each other to change really the environment that these animals are dealing with.Alonge: Yeah. Totally environment. Yeah. There's not one variable. There's a lot of different things on the one hand. It seems, you know, it's a cool system. Your question is awesome. But because this impact is so large scale, is that the type of work that you feel doesn't have necessarily like this immediate applied conservation goal, and there's something bigger that you're really striving towards?Wrensford: Yeah, no, that's an excellent question. Um, I think with the chipmunk specifically, it's difficult to think of immediate applied conservation goals. So neither of these chipmunks are listed under IUCN is vulnerable or near threatened or anything like that. Although you can talk a lot about how you feel about the actual criteria for listing species. Um, that's another, that's another conversation, but I think in terms of applied conservation effects, I think understanding sort of how animals are reacting to these, these changing climatic conditions in their habitats over short scales, I think may, may not necessarily translate into like, okay, here's our, here's our management plan for endangered species of interest. But I think it really will inform how we think about how animals are reacting to climate change. You know, a lot of, a lot of, uh, how we talk about animal reactions to the climate change is a lot of doom and gloom.Wrensford: You know, it's a lot of, you know, we're going to lose X amount of species by 2050 or, or things like that. And while it is a very dire scenario for animals, like we're going, we are going to lose a lot of diversity. And that's true. I think the scenario is a bit more complicated than that animals are dynamic entities, right? They're responding and adjusting and adapting as they always have. The question is, are those responses and are those adjustments, are they quick enough to track with the kind of pressure that we're placing on them? And that's an open question for a lot of animals.Alonge: I like your optimism in the face of everything going on. You know, I think there's a, a realism, but also an underlying optimism. And that is very refreshing and probably good for all of us to hear.Wrensford: I'm happy to provide that. You know, like I sometimes I feel really down about the state of the world too, and, and, you know, and I think it's, and it's going to be hard, but I think also animals are amazing and that's kind of one of the things I've always, I've always felt. And I continue to feel the more I study them, the more I learn, you know, and learn how dire the situation is. But I also learn how amazing the animals we share the world with are, and kind of what they, they have at their disposal to really adapt.Alonge: So do you have a sort of dream species that you could study?Wrensford: I have a few, yeah. There was a, there was a time I really wanted to work with snow leopards. Like I've always loved snow leopards. I always thought there's kind of, you know, there's kind of this mysterious romantic animal.Alonge: Yeah. Mysterious, but glam.Wrensford: Exactly, you know, you ever seen like a picture with one biting its tail. It looks like a little feather bow. They're super cute. I love them. Um, but I've always had this sort of, sort of pipe dream that I would go out to like the Hindu Kush mountains in Pakistan and like go chasing snow leopards or something don't think that'll ever happen mostly just because they're just so rare and so hard to find, you know, people, even with people who were using camera traps. So they're not even going out looking for them in person. We'll see maybe a couple in a year. Yeah. Because they're pretty rare, pretty loosely populated and they have huge home ranges. So that's, that's the animal that got away, I would say.Alonge: Yeah. Unexpected. Yeah. From yellow-bellied marmots to snow leopards, maybe in the future, don’t rule it out.Wrensford: Maybe you never know, you never know fingers crossed.Alonge: Okay. So were you, you mentioned earlier that you were sort of always interested in animals. Were you also always interested in nature more generally or the outdoors?Wrensford: Yeah, I would say so. Um, so I was born in the Caribbean, spent a couple of years there and then moved to Southern Georgia. And so one of the great things about Georgia is it's, especially in the Southern part of the state. It's one of the, one of the coolest ecosystems in the world. I think it's a lot of, a lot of reptile and amphibian diversity. You're so far South that you're starting to get a lot of warm weather stuff. You don't really get in the rest of the country and sort of growing up around that really kind of really solidified my love for nature. Um, just kind of being out there, flipping logs, looking for lizards and stuff. It was a really good time. Um, I was a Boy Scout for a while too. And so that's kind of what, like, so I was always in animals, but then kind of Boy Scouts is what it got me into, the more outdoorsman side of things.Wrensford: So camping and hiking and backpacking and things like that. Um, and so that was a really valuable, um, experience for me, I think was just being able to get out there in a way that I probably wouldn't have had to otherwise. Right. My family wasn't super outdoorsy. You know, we didn't do like family trips to park national parks or state parks or things like that. So it was often through sort of my, the Boy Scouts and also I volunteered at our local zoo and it was sort of through those two outlets is what really kind of got me hooked on nature and, and working with animals.Alonge: Yeah. The work you do has this big natural field work component. So some people do field work because they have to, but some people have field work as a part of what they do because they love the whole experience of it. So I'm guessing that you're on the ladder part of it,Wrensford: I would say so. Yeah. I think nature, I think nature brought me into science, although I was always surrounded by science too. Like I think I've always liked science large too. So those kinds of work parallel with each other, but I don't know if I, if I didn't love nature the way I do, if I would be doing science or at least doing research science, you know, so yeah. I definitely think, uh, nature is what pulled me into, uh, pursuing, pursuing a graduate degree, doing research.Alonge: So if you're just joining us, this is The Graduates on 90.7 K A L X Berkeley. And we're here with Kwasi, Wrensford, a behavioral ecologist in the Department of Integrative Biology. How do you continually find inspiration in the science that you do? Because it is often challenging.Wrensford: Yeah. Yeah. It is. It can be very challenging to, you know, keep the inspiration going. I think in academia and research, we ask a lot of, of ourselves, you know, that we're this project idea driven mode of life, you know, where we're constantly being asked to come up with novel perspectives and takes on things. And yeah, you know, you can just do that all the time. Um, but I think one of the main ways that I do that I stay inspired. It's just talking to people. I think one of the great things about integrative biology that my home department is, is that folks in that department do such a wide range of things with a wide range of approaches and questions and systems and, you know, just interacting with people in the department. I can, you know, get perspectives that I never would have gotten otherwise. Like, you know, I'm this summer collaborating with, uh, with a fellow person in the department who works on biomechanics. If you'd asked me like three or four years ago, would I ever have even remotely thought of doing biomechanics work in my life? I would have been like, you're crazy. But you know, that's just comes with talking to people and identifying those mutual, these mutual interests. And that's really, what's been pushing me in my time in grad school is just being surrounded by all these awesome people.Alonge: Please tell me you're building a robotic chipmunk?Wrensford: I don't, I don't know if we're going to do a robotic chipmunk. Robotic squirrel in general is in the works. So I'm collaborating with Lawrence Wang who's in Bob Full’s lab. And they been really interested in this, the jumping biomechanics of squirrels and using that to inform building an arboreal robot. Yeah. And so Lawrence and I are gonna go out, he's gonna come out with me over the summer. We're gonna film the chipmunks and sort of compare how good they are at jumping compared to like the tree squirrels on campus. Yeah. But yeah, it's just stuff like that, you know, that, um, that we, I have access to people like that so easily here that's really been making the job easier.Alonge: Yeah. Yeah. Um, how about the questions that you come up with for your research? How do you shape those or yeah. Is that also coming from dialogue and conversation or do you, is your strategy more, you know, gather all your thoughts, do tons of reading, what's your process?Wrensford: Um, so definitely both to be short. Um, I do a lot of reading. Um, my first year of my PhD was just mostly reading, but I think the questions I've chosen have made it, so that like kind of the range of kind of been everything from the nature of animal cognition to like broad climate modeling to thermal physiology. And so I've cast a very wide net and sort of the things I've read, but it's all been very useful in solving very helpful, but then sort of also taking those readings and bring and assimilating that knowledge and integrating it, but also sort of regularly sort of presenting that to people around me. You know, I think one of the things that's a temptation when you're in grad school is to kind of turn inwards, you know, that you're this lone scientific entity in your, you know, you're supposed to take all of what's around and assimilate and come up with these perfectly formulated ideas and be this sort of intellectual juggernaut.Wrensford: And, you know, that's not really, that's not the case. I, I don't want to make assumptions for people, but I don't think that's the case for most of us, if any of us that, you know, we come up with perfectly formed ideas in a bubble. Right. And so I think it's really important to have that time to sit with your thoughts and assimilate them, but also to make sure you're sharing those thoughts with the community around you and getting feedback and getting input. And again, using that, that diverse community to sort of workshop your ideas and give you alternative perspectives,Alonge: Community aspect of science research is probably something that a lot of people don't quite realize unless you're inside of it. And yeah, I would agree with you that I think it's extremely valuable and we certainly can't speak for everybody. Some people might prefer to work in a more independent way, but I think that you can really reap a lot of benefits from sharing your ideas and getting feedback and all that. So in terms of sort of digging into understanding science and trying to understand more about questions that might be interesting to our listeners or to other people, do you have any advice for how best to sort of seek out information if people are interested in science and a topic where, where are the places that they can look or who can they talk to?Wrensford: Right. Right. So I think so we live in a really great time for just finding information. Right. I think information is available in a way it's never been available before. I think the easiest or the best places I've found for just really kind of accessible, easy to digest science is YouTube. Like, I love science YouTube. Like there's so many science, YouTube channels, things like, like things that Hank Green's doing, like Scishow and, um, and MinuteEarth. And there's so many cool science channels on YouTube. Now like at your fingertips, they give you in like two to five minute videos, you can learn so much about a topic.Alonge: Yeah. And the visual is probably so much more interesting and like captivating then sitting down to read like a textbook or something that you could get from a library.Wrensford: No, exactly. And so I think if you're just wanting to get your, get your toes wet, I think that's the best place to go. Um, I'm also a big advocate of, I love museums and zoos and other kind of, sort of in person, academic science outlets like that. Um, I worked at a zoo, so I'm a little biased, but I think a good zoos are some of the best places to learn about animals you could ever find anywhere, um, museums as well. And then also being in the Bay Area, we've got so many cool, uh, museums.Alonge: Yeah, we're very lucky. What did you do when you were volunteering at the zoo previously?Wrensford: So I worked in the, I worked as a volunteer with the education department, so I wasn't as directly involved with sort of the broader zookeeping animal care, but I helped with animal care for a lot of our outreach animals. So the education department had a lot of, um, uh, sort of smaller animals that we brought out to programs. Most of them were rescues or, um, re rehabbed animals that, um, weren't fit for being released in the wild anymore. So we would hold on to them and take care of them and use them as ambassadors for the zoo. And so I did a lot of work taking care of those animals, but also doing presentations as well. So, um, I remember one of my favorite things ever is there. I could go out and talk to group people with a hawk on my arm. Um, and just, and there's something about, you know, just talking about this animal while you're holding an animal right there for people to see and be in proximity to, there's nothing else like it reallyAlonge: A memorable experience for you, but also them. Right? Yeah. That's really cool. And do you teach at all as a graduate student here?Wrensford: I do. I do. So, um, I, I haven't taught every semester I've been here, but I've been able to, I've been lucky enough to teach, uh, animal behavior. Uh, it's our kind of upper level, um, undergraduate animal behavior course. And so we do everything. We'll talk about the evolution of behavior to sort of the mechanisms underlying behavior, whether it be the brain or hormones. And we also talk a little bit about the more ecological society of behavior and how animals interact with themselves, each other in their environment. And so I had, I was lucky to teach that course, and that was a ton of fun.Alonge: Sounds right up your alley.Wrensford: Yeah. It's quite there. Yeah. Um, and then the other class I got to teach was, uh, a, another sort of behavioral course. This is a course called behavioral ecology, but this was more of a lab and field oriented course, a lot more hands on. So we had a lab section that met every week and we also did field trips about once or twice a month. Um, and so that was sort of similar material to the animal behavior course, but putting it in the context of a more inquiry based approachAlonge: Yeah. And where students can maybe develop some of their own ideas and questions. Yeah. It's so valuable. I think as an undergrad myself, I never actually got involved in research, but I really can see how that can be a really impactful experience. And maybe like, maybe those are the types of things that give someone their first exposure to scientific questioning and might shape their whole trajectory. So totally. Yeah. Have you been able to sort of integrate and include your area of expertise when you're teaching and share some of your experiences in the field or some like preliminary sneak peaks about the findings you're having with students and have conversations about your work?Wrensford: I try to, um, it, it depends on the subject depends on the day, but I think, especially in sort of in the aspects of both courses where we're, we're asking more of the students to sort of formulate their own ideas and, and bring some more of themselves to the process. I think hearing my experience sort of hearing how I sort of struggle through my own work or, or that perspective I think is really valuable and really helpful. So I know in the, in the behavioral ecology course, we have, each of them sort of do, we do experiments with the local campus squirrels. And we have each of the groups sort of devise their own experiments and data collection protocols to work with the squirrels. And so, so there's a whole process and the students and how they develop their methodology, develop their questions and everything like that.Wrensford: And as a, as a GSI, as, as their instructor, it's kinda my job to sort of guide that process and check in with them pretty regularly. And I often can make analogies to my own work, especially like when they're developing the methodologies, I can, they don't have to make the same mistakes I did when I was formulating my own experiments. So my experiments that I've been doing recently, even a lot of behavioral experiments, I'm doing a lot of filming and observations and in these sort of apparatuses that I can build out in the field. And so most of that time was spent with a lot of trial and error. Like how do I get this apparatus to work? How do I keep the chipmunk inside? How do I keep it from escaping? Like, how do I get my camera angles just right. It's all that kind of minutia that you don't ever really think about, especially if you're kind of new to the more active side of science. Right. And so bringing that to bear, bring that experience to bear for the students when they're developing their own ideas, I think is invaluable. I hope they really appreciate it.Alonge: So do you have any sort of final thoughts for how we can all act a little like behavioral ecologists in our daily lives? What kinds of things can we look for?Wrensford: Yeah. So I think to be a bit more like a behavioral ecologist in your daily life, I think whenever you see an animal, any animal, even your pet, when you see it, uh, doing its thing, you know, living its life, um, I just kind of wonder, just wonder why. And I think that's, um, that seems kind of simple in, but I think, you know, when you see an animal out there, you just think that that animal is, is an individual with its own needs and motivations and, and roles. And it's an ecosystem environment and those are, and those roles are dynamic and complex and those roles aren't in a vacuum either. And I think that's really important is that when we see things, when we observe things, always observe things in the larger context.Alonge: That why question is yeah. Much bigger than alpine chipmunks in the Eastern Sierras. Yeah.Wrensford: I agree with that.Alonge: That's it for this week. Thank you Kwasi for being here. It was awesome to chat with you.Speaker 3: Thanks for having me, Mattina. I had a blast.Alonge: Cool tune in next week. Again, this is 90.7 KALX Berkeley.
4/25/2020

Eli Mehlferber

Andrew Saintsing: You're tuned into 90.7 FM KALX, Berkeley I'm Andrew Saintsing and this is The Graduates, the interview talk show where we speak to UC Berkeley graduate students about their work here on campus and around the world today, I'm joined by Eli Mehlferber from the Department of Integrative Biology. Welcome to the show, Eli.Eli Mehlferber: Hey Andrew. Thanks for having me.Saintsing: Great to have you here. How are you doing?Mehlferber: Pretty good. You know, all things considering right now.Saintsing: So, Eli, I hear you study tomatoes?Mehlferber: Sort of, um, I studied the bacteria that live on tomatoes, specifically the bacteria that live on the, uh, leaf surfaces.Saintsing: Okay. So you study bacteria on the leaves of tomatoes.Mehlferber: Mhmm.Saintsing: Why?Mehlferber: Yeah, I'm looking at the, uh, host microbiome interactions. So trying to understand how the bacteria living on an organism can provide different functions for it. So in this case, it's how bacteria that live on the leaves of tomatoes to protect them from disease. But you could also apply it to like the bacterial living in the guts of you or I.Saintsing: Oh, cool. Yeah. I hear about microbiomes all the time. You've got to eat yogurt, right?Mehlferber: Yeah. Get the active cultures.Saintsing: Right, right, right. So wait, like plants need bacteria to get rid of diseases. So plants are like, like what kind of diseases are plants fighting?Mehlferber: Well, plants can get all sorts of diseases. Uh, viruses, bacteria, uh, fundal pathogens, all of that stuff. Uh, I focused mostly on bacterial. Uh, so I study a lot of different bacteria, but the, uh, model pathogen we use is the bacteria Pseudomonas syringae. So that causes bacterial spec.Saintsing: What's bacterial spec?Mehlferber: So if you've ever seen a tomato or a tomato leaf that has a bunch of tiny little black dots on it, that's bacterial spec.Saintsing: What does it do? Is it, does it kill the plant? Yeah.Mehlferber: So it's a, uh, yeah, it'll infect the plant and eventually kill it. Uh, most tomatoes that we grow for, like food production are resistant to it, which is good, but it is a breaking out in some new agricultural cultivars. So, kiwis, for example, right now are super, super sensitive to a certain strain of Pseudomonas syringae that's like wiping them out.Saintsing: Okay. Wait, so people have engineered or like bred tomatoes to be resistant to those bacteria?Mehlferber: Yeah. So most cultivars that you would have out of in a field are resistant to it, but we studied the more sensitive ones in the lab.Saintsing: I got you. And the, and so kiwis are having a breakout, so they're not resistant to it, but they generally don't encounter it.Mehlferber: Uh, so previously they hadn't. It usually infects leaf tissue, but in kiwis it's, uh, the bacteria is actually mutated. And so now it affects the wooden tissue. So it causes, uh cankers. I can't remember the exact name of the disease. I think it was like a bleeding canker disease. Yeah. So it causes this gross red sap to like leak out of the trunk of the kiwi. So it looks kind of like it's bleeding and it'll kill the whole tree.Saintsing: Yeah. Gross. Wait, does this bacteria, I guess, like, can you even get a fruit from it if it has, if it's infected?Mehlferber: Uh, I think it sort of depends on when it was infected and how extensive it is, but it definitely does impact yield.Saintsing: I see. So you study how these plants are using microbiomes that would prevent these bacteria from infecting them basically.Mehlferber: Yeah. Sort of, um, I focus a little bit more on the microbiome side. So there are two ways that a plant can be protected from a pathogen, a bacterial pathogen. Um, one of them is through the plant immune system and that can also be triggered by the bacteria living on them. So you can have a good bacteria. Let's just call them that, uh, kind of get the plant immune system ready to go. Sort of like the, uh, theory of immune priming, like humans. So you want to be exposed to a lot of stuff. Your immune system develops correctly. Um, it's not exactly the same implants, but sort of like that. So if you have bacteria that are say closely related to a pathogen, um, that could make the plant more able to fight off the pathogen when it eventually needs it. So that's one. Yeah.Saintsing: You're saying that plants have an immune system.Mehlferber: Yeah. Very advanced immune systems actuallySaintsing: Wait. So like, so we have what the like white blood cells that roam around and target things that are foreign right. In our, in our bodies. That's something similar.Mehlferber: Uh, it's actually a really cool how different it is. So humans have what's called acquired immunity. So you have to encounter something first and then your body will mount a defense to it. Plants have innate immunity. So they're basically born with all the immunity that they'll ever have. And it's a regulated, it can be regulated plant-wide through hormone signaling, but fundamentally it happens on a cell by cell response. So single cell has everything it needs to fight any pathogen that it might encounter that it's prepared for.Saintsing: So, okay. But you, so you're saying that it's born with it basically that it's innate, but that different cells might be prepared for different foreign invaders.Mehlferber: Um, sort of, so it's innate and all of the cells are prepared for all of the foreign invaders or at least capable of responding to all of the foreign invaders that the plant was born with, the ability to deal with. It gets pretty complicated.Saintsing: I see. Um, okay. But, so you were saying that the, that if a plant has bacteria that are similar to the potential bad bacteria, that it needs to fight off than it is more prepared to fight back.Mehlferber: Yeah. Because it will basically see that bacteria and recognize it. Um, and a lot of the immune system in plants uses conserved recognition sequences. So we told them, uh, MAMPs, uh, Microbe Associated Molecular Proteins. Um, and so those are shared across a wide, wide swaths of bacteria. So if you see a MAMP, for example, uh, that's similar to that of a pathogen, then the plant will recognize it and start responding. And because it started responding in that case too early, because there wasn't actually a pathogen there it'll still be ready if a pathogen comes later.Saintsing: Oh, okay. So a plant. So like in the seed, the embryo has all of these recognition has all the abilities to recognize these pathogens, but once it grows up, then it's actually starting to see these pathogens. If it's been exposed, then it ramps up the defense to those pathogens earlier. Or later, depending on when it encounters. Cool. Okay. So,Mehlferber: So yeah, so that's one, that's one way that the, uh, plant can be protected from pathogens by the microbiome. Um, and that, that's not really what I study all day. That is super interesting. So then I looked at that other way, which is more of an ecological framework. So if you have the bacteria living on the plant, uh, they perform certain roles and they have different things, et cetera. So they take out all of the niche space on the plant. And if you have bacteria already on the plant that aren't pathogens that use all of the same chemicals that are pathogen would need, uh, it can't establish at all to start with.Saintsing: So how does, how does a plant build a good community or like yeah. How, how would it select for that?Mehlferber: That's the question. Um, so we know a little bit about how that works in the rhizosphere, so that's the root structures of the plant underground. Um, and so the plant can release different chemicals that attract certain bacteria, and then those bacteria will drive away other bacteria basically by out competing them. So thatSaintsing: So those chemicals are also innate, like the plants it's primed to release those chemicals to attract those bacteria when it's in its seed and starts growing.Mehlferber: Yeah. All genetic. Um, so we know that happens on the roots. We don't know if that happens in the leaf tissue yet. So that's one of the things that's super interesting is seeing if different genotypes, um, specifically select for different types of bacteria.Saintsing: So, the plants and the roots they have, it's they also have like a bunch of fungi that are down there. Right. And so like, those fungi are also interacting with the bacteria and everything. And like, it's like, it's kind of,Mehlferber: Yeah. It gets pretty complicated pretty quickly.Saintsing: Okay. But you don't, you don't really focus on the roots or,Mehlferber: Uh, I don't really focus on the roots and I don't really focus on fungi either. So,Saintsing: So, but there aren't really those fungi, like on the leaves, like you would,Mehlferber: There are fungi on the leaves, they're actually a ton of fungi on the leaves. So I'm sure that they do play some role. Uh, we don't really know exactly what yet. And so, so fungi are a little bit harder to study in the community since then bacteria, because so bacteria all have, um, uh, 16 S rRNA. Um, so the ribosome has a certain conserved region on it. Uh, and all bacteria have a certain segment that's conserved. So you can design a primer and perform PCR and amplify, basically any type of bacteria.Saintsing: So, we should say like, so what is the ribosome?Mehlferber: A ribosome is the, uh, part of the cell that produces proteins. Um, it's where they read the RNA and then construct protein basically.Saintsing: And so those are like really important to the cell. And so those kind of stay consistent in,Mehlferber: So there's some parts, the parts that bind to the different segments of our RNA, for example, it kind of has to be a certain way or else it won't fit. So there's basically never change in bacteria, or if they do very slowly. Um, so you can kind of design a primer, that'll match that sequence and it'll fit to like 99% of bacteria or something. You can amplify that. So, uh, PCR, Polymerase Chain Reaction, where you use some template to amplify a certain targeted region, uh, you can use that and amplify all of the 16 S RNA sequences in a sample, for example. And, uh, once you have all of those RNA sequences, you have the conserve bit, so you can design a primer, that'll amplify all of them, but you also have some highly variable parts later on. And then you can use those to distinguish between the different bacteria that are in the same sample. Cool.Saintsing: So this is how you're studying, um, how you're finding out what bacteria you're looking at, basically. Yeah. You just kind of like take some leaves, you grind them up and you just look at what's going on using these, uh, you just kinda are able to select for the specific bacteria ribosomes. That's why we're focused on ribosomes. Cause you have like specific tags or, um, something that you can target those particular strands of DNA.Mehlferber: Yeah. So that's why it works very well for bacteria. Um, and then fungi have some analogs to that, but they're not as universal as the 16 S RNA one is in bacteria. So it's a lot harder to study the whole fundal community.Saintsing: I see. Right. So, we got distracted, sorry. I distracted us from the study of bacteria. So, but you're focused in, on the bacterial community in leaves. Um, so you were saying that the rhizomes, the roots of the plants, uh, release proteins or chemicals signals that like get, get the bacteria to come to them. I guess these bacteria are just like living in the soil that the plant is going to grow in. Right. Exactly. And then, but it's less clear how the leaves recruit these bacteria.Mehlferber: Mhm. So it's, so it's pretty easy to figure out where the bacteria in the soil come from, because there's a lot of soil around the plant and it can kind of filter out which bacteria it wants to associate with or not. Whereas the leaves being above ground, there's no clear reservoir. So we know that bacteria come from the air and from rain and from other plants and stuff.Saintsing: Wait they come from rain?Mehlferber: Yeah. So a lot of bacteria come a lot of, uh, colonization events on the leaf surface come from raindrops.Saintsing: Cool. Yeah, because they actual are, are up in the, up in the air, like what happens? Do they like to go up on water droplets and then come back down? Like, is that-Mehlferber: Yeah exactly, So Pseudomonas syringae specifically is really cool in that, uh, being a pathogen that's very well adapted to spreading to different plants. So it has, uh, an ice nucleation protein that it produces. So they'll actually get set up in the clouds and then cause snow. So it drops out of the clouds and then it lands on a plant and then it causes the plant leaf to freeze, which breaks the leaf and then it crawls inside and does all the damage.Saintsing: Dang. That's crazy. That's really cool.Mehlferber: Yeah. It's super cool. If you, uh, if you've ever actually gone skiing, you've seen the effects of this because most fake snow is produced using that ice nucleation protein.Saintsing: Oh, cool. Wait. So like, even when, even at like, you know, room temperature, it could freeze things using things like ice nucleation protein or,Mehlferber: Um, not necessarily room temperature, but well above freezing.Speaker 3: Right. Okay. So a bunch of different ways that the plants can get these bacteria, rain, other plants. And then, so it, you're kind of studying like how it filters out, how it selects for the good ones basically?Mehlferber: Sort of, I'm a little bit more focused on how the bacteria that are already there, um, select for what comes later. So how does the community that you have, um, influence what new members can join basically?Saintsing: Is it by chance though? Like what initial community forums? Cause it's like rains down whatever's in the air, around them and other plants.Mehlferber: A lot of it definitely is due to chance, so random. Um, but we do think that either the plant has some ability to choose which bacteria it wants to promote, um, or different bacteria do better or worse on the plant. So they're more likely to be there just as there's more of them sort of floating around. Um, so we see pretty, pretty replicable patterns on like leaves over time. And so communities are definitely changing and a lot of it is random, but there do seem to be some rules and I'm sort of looking at what the rules are that decide who gets to be there and how well they're going to doSaintsing: What, what are these kinds of rules?Mehlferber: Uh, so it's a lot of ecological stuff. So you've got everything from like dispersal. So how well the bacteria is able to travel between leaves basically or travel through the rain, et cetera. And then you've got a lot of competition based stuff. So if different members in the community don't get along or say they share the same resource that they use, they're going to compete for that resource. And so some bacteria are significantly better or worse at doing that and they have different strategies for competition. So that's sort of what I focus on the most is looking at how bacteria compete with each other and how that shapes the final community that you'll see when you eventually sequence a leafSaintsing: What's bacterial competition? Like what are the, what do they do to each other?Mehlferber: Uh, all sorts of things. So you have a direct and indirect competition, so they can either produce antibiotics to poison each other basically. Um, or they can just try and grab up all of the shared resource more quickly than the other one.Saintsing: Wait, so, uh, a bacteria, a bacterium, I guess that can produce an antibiotic would necessarily have to be, uh, resistant to that antibiotic, right?Mehlferber: Yeah.Saintsing: So the other, how does, how does it get that capacity?Mehlferber: Short answer: evolution. Longer answer: horizontal gene transfer. So bacteria have plasmids, um, and so they can try to share genetic elements between each other. So I think that's how some antibiotics spread throughout communities and then other stuff just, uh, evolving to produce toxins or producing, um, secondary metabolites. So secondary metabolites are basically anything that bacteria puts out. So it takes in something and produces sugar, other things as a byproduct. So they can evolve to produce secondary metabolites that, uh, make the environment less, uh, less ideal for other bacteria. So they could like increase the pH for example of the leaf, um, and made it so other bacteria can't grow as efficiently or something like that.Saintsing: Okay. So fierce competition on a plant leaf.Mehlferber: Yeah. There's a lot going on.Saintsing: So are you studying specific interactions? So you said you were looking at that specific bacteria that causes the spec on tomato. And so you're looking at, are you looking at specific other bacteria that, uh, try to, I don't know, dissuade it from populating the leaves that it's trying to get on?Mehlferber: Yeah, exactly. So I have, um, a bunch of bacteria in the lab that I've collected from, uh, field samples. So just going out to a bunch of tomato fields and grabbing leaves, uh, pulling off the bacteria and seeing what grows, and then I'm looking at a bunch of different, uh, characteristics that those bacteria have and trying to see how important different things are in deciding how well they'll compete, uh, with the pathogen and with each other.Saintsing: What kind of characteristics?Mehlferber: Uh, so everything from just sequencing them and looking at their genome suit and look at what potential they have metabolically by sequencing them. SoSaintsing: Metabolically to like produce those secondary metabolites that you were talking about, or?Mehlferber: To produce that in their metabolites and to consume different types of sugars. So sugar is the limiting resource on the leaf surface. So you have to be very good at getting sugar, if you want to be a successful leaf bacteria. Um, so looking at how those genomes predict, uh, how well they'll do, um, eating sugar basically, and then actually testing how well they do at eating different types of sugars and how many of those sugars do they share and how much better are each of them than each other and the pathogen.Saintsing: Right. So is it just like a plant can't avoid releasing sugar onto its plant or onto its leaf surface or like, is it actually, is that part of the recruitment process to put those sugars out?Mehlferber: That's a really good question. Um, so we do know that bacteria can actually change what sugars are being produced, uh, by releasing different compounds that mimic plant hormones. So that's super cool. So the bacteria definitely can kind of shape that environment a little bit. Uh, and we don't know how much the plant is actively releasing these sugars, uh, to promote good bacteria living there or it's, I mean, some of it's just doing the wheat out of the plant surface regardless. Um, but the plant probably has some ability to modulate it. We just sort of don't know how much.Saintsing: Right. But I mean, ideally it wouldn't want to release sugar, right. It would want to keep that for itself.Mehlferber: Well, you could think that, so the bacterial pathogens, they live on the leaf surface for a little while and they eat sugar and then they eventually moved into this, uh, into the plant. So they'll move to the inside of the leaf and then sort of start writing habit there. Um, so potentially the plant does produce sugar because then other bacteria will live there and they'll prevent the pathogen that could do more damage from dating there. So the pathogen would probably do some amount of damage whether or not there was sugar on the leaf surface. Depending on exactly how it enters the plant and what its life cycle is like.Saintsing: Do you have like any, I dunno, things you've already found or like results you've already gotten to in your research?Mehlferber: Um, so something that I've seen the most is that, so a lot of this is definitely still in progress. Um, but I definitely have seen a lot of, um, difference in the bacteria and their ability to consume these triggers. So some bacteria just seemed to be very well adapted to living on the leaf surface. Um, and that sort of makes sense because you see certain bacteria that are much more dominant, uh, whereas other bacteria, or just really bad at consuming sugar and also pretty bad at living on the leaf. So it's really interesting to think about, um, some of these bacteria probably love being on the leaf. So the pathogen definitely does, um, some of the other good bacteria. So, uh, they, they probably do, but some bacteria probably just, it stuck there, like they just happen to float by and land on leaf. And that's not really where they wanted to be. Um, so I think it's really interesting. Um, just trying to figure out what bacteria actually wanted to be on the leaf, you know, uh, to kind of anthropomorphize them and which bacteria didn't and see how that changes what we know about leaf communities.Saintsing: Right. Yeah. There's so many bacteria and individual bacteria. It was just kinda like randomly, like, you know, maybe life will work out for you. Maybe it won't.Mehlferber: Yeah. And I think that sort of applies to like the human diet too. I mean, we eat a lot of stuff that has a lot of bacteria on it and some of it wants to be there. Some of it doesn't some of it does really well and some of it does fine, but kind of just ended up there by accident.Saintsing: Yeah. We're eating a lot of a plant leaves actually. So do we, um, I don't know. Do you ever see similarities between plant microbiomes and even microbiomes based on diets that people have?Mehlferber: You know, that's a really good question and that would be a cool thing to look into.Saintsing: Have you always been interested in studying, um, bacteria?Mehlferber: Uh, yeah. Um, so it's kind of funny. I actually ended up here sort of by accident.Saintsing: Here as in Berkeley or as in this field?Mehlferber: In this field. Um, so I ended, I started out in undergrad studying fruit fly genetics and, uh, beetle genetics. So it's sort of more of a, uh, yeah, more of a geneticist. And then I actually had an issue with one of my big studies in fruit flies where, uh, I was looking at the effect of bacteria on their ability to consume, um, lower high protein sources. And I kept running this one bacteria that I just couldn't get rid of and it sort of messed up the whole study. Um, but it got me thinking about how important bacteria are for their hosts. And then I, uh, did some reading and realized that that sort of what I wanted to do for grad school. So I switched gears completely, um, and then moved into looking at bacteria. And I was looking at bacteria for a little while and it actually took me awhile to realize that I wasn't really a microbiologist. I say, cause I would say, I would say that microbiologists look more specifically like what bacteria do on like a bacteria by bacteria and basis. And I'm actually more of an ecologist where bacteria are cool and what they do is super cool, but what I'm most interested in is how they interact with each other and how communities form and develop and more importantly why.Saintsing: I see. So you didn't want to be just limited to a single bacteria, bacterium. Yeah. Right. That's cool. So you just, all of a sudden were struck by bacteria and like, because they were messing up your science. Yeah. I guess that's kind of like, um, that's what they say. Right? Like science, there's a lot of accidents and luck. Right. And everything that happens.Mehlferber: So this is definitely a lucky accident, very annoying at the time. But in retrospect, glad I ended up here.Saintsing: Yeah. How did you, uh, how did you get into research and undergrad?Mehlferber: Uh, so I always knew that I wanted to work in science in some way. So even as a little kid, I always loved science classes. I thought they were super cool. Um, and at that time, everyone was like, Oh, so if you're into science, you'll be a doctor. And I was kind of like, Oh, I guess maybe I'll be a doctor. And then turns out I really hate blood. Um, and you sort of need to be able to work with blood, to be a doctor and make it through med school. Um, so I was like, okay,Saintsing: The bleeding cankers on the one, uh, one plant freak you out?Mehlferber: That's actually fine. As long as it's not human, I guess. Um, so I was like, okay, I'm definitely not going to be a scientist. So I was like, okay, I'll try that. Um, so I knew that I wanted to do science when I was coming into undergrad and I honestly just came to campus and wandered around, passing out my CV, which at the time I had worked at Burger King, no qualifications whatsoever, but just wandered around from lab to lab, handing out my CV and said, Hey, I'd love to work in your lab if you have a space for an undergrad. Um, and I just happened to wander into the office of the woman that became my future boss. Uh, and she had just moved her lab, uh, into the building. And this was, I think her first day actually in lab, I walked in and handed her my CV and she's like, yeah, I'd love to have an undergrad you're hired. And I spent five years there.Saintsing: That's pretty cool. Yeah. Another case of like a lucky accident, right. You just like stumbled in, there you go.Mehlferber: Yeah. Just sort of stumbling through science, one happy accident at a time.Saintsing: Yeah. I mean, you know, don't knock it, it all works. I guess people don't know what they don't know. Right. You just kinda got stumble through most of the time.Mehlferber: I mean, I figure if you end up doing, I think a lot of like success is sort of luck. Not necessarily, not necessarily like blind luck, but if you know that you liked something and you're interested in it and you're good at it enough that you can just kind of wander somewhere and end up doing okay, then maybe that's where you're supposed to be.Saintsing: Yeah. Yeah. The secret is just like starting to wander in the right place. Right?Mehlferber: Yeah. Yeah. I think what is it? Luck is what happens when a serendipity meets preparation.Saintsing: Nice. True. What kinds of things did you, uh, what did you like about science growing up?Mehlferber: Uh, that's a good question. Honestly, I guess it was that it seemed to like it that the field was not complete. There was some life to it. Like science is still happening all the time and we don't really know any, I mean, in the grand scheme of things, we don't really know anything yet. Um, so people are always figuring things out and everything else always just seems sort of like, I don't know, a little bit more static or that move more slowly. So I just thought it was cool to be able to work at something where it's your, the person putting stuff in textbooks. I always thought that would be interesting.Saintsing: Yeah. You wanted to work at the frontiers of things. Nice. What do you, uh, what do you think you'll do after grad school? Do you think you'll, uh, be an academic?Mehlferber: Uh, that's a great question. I hope so. Um, so I've definitely, I definitely would like to be in that to them, but I know that the job market isn't necessarily that great in this field. So I've definitely been doing a lot of work with, um, more private sector stuff. So I worked with a startup right now. Um, and I'm trying to get more experience in the yeah. In the private sector. So I can hopefully at least get a job.Saintsing: I mean, I, you know, you study like how you can maximize yields of crops. So I feel like you'll be fine. Right. People gotta eat.Mehlferber: That's true. Tomatoes are important.Saintsing: Yeah. And your, your bacteria affects kiwis too. You know, everyone loves kiwis. So it looks like we're running out of time on the interview, but usually at the end of the interview, we have a moment where guests can address the audience on, you know, issues related to their research or anything they'd like to talk about are, um, I don't know, science in general or whatever in general. Do you have anything you, any thoughts you'd like to leave, uh, the audience with?Mehlferber: Yeah. I would just end it by saying that something that I definitely believe is that everyone's sort of a scientist in that everyone has curiosity about something or another. Uh, and it's really cool and I feel really lucky that I happened to get paid for it, but I think that everyone should sort of just follow their curiosity and always try and learn. Um, yeah. And just go through life with that mindset because there is a lot that everyone can learn and there's a lot out there that people don't know, so everyone can contribute something. Um, and it makes life pretty interesting when you're trying to push at the forefront of that.Saintsing: Yeah. Cool. Hopefully everyone will go out and study something today. I've been speaking with Eli Mehlferber from the Department of Integrative Biology. And we've been talking about his research on, uh, tomato plants and their bacterial communities. Again, thank you so much for being on the show.Mehlferber: Yeah. Thank you for inviting meSaintsing: Tune in, in two weeks for the next episode of The Graduates.
4/20/2020

Greg Meyer

Andrew Saintsing: Hi, you're tuned into 90.7 FM KALX Berkeley. I am Andrew Saintsing. And this is The Graduates, the interview talk show where we speak to UC Berkeley graduate students about their work here on campus and around the world. Today, I'm joined by Elisa Visher from the Department of Integrative Biology. Welcome to the show Elisa. It's great to have you here. So Elisa, you study viruses, is that correct?Elisa Visher: Yes, I do. And I kind of always backed back from that statement because while I study viruses, I think a lot of times what people hear when I say that I study viruses is that I study kind of the really important human pathogens that you hear about in the news today. So things like Ebola or the flu or HIV, and I did actually study flu for a while, but right now, what I'm really focusing on is kind of generalizable theories about how infectious diseases and viruses evolve, and also how they shape broader ecological and evolutionary patterns that we see across the globe today.Saintsing: Okay, interesting. So how do viruses actually shape ecological and environmental patterns that we see?Visher: So there's a couple of key kind of important observations that viruses and infectious diseases more broadly are implicated in. So a lot of the things that infectious diseases seem to explain, actually have to do with diversity. And so some things that we think that infectious diseases affect are how much genetic diversity is maintained within populations. Um, so there's one theory called the red queen hypothesis. That explains why plants and animals were selected to have sexual reproduction and then infectious diseases and parasites and pests more generally have also been implicated in species diversity patterns. So one of the big patterns that we see across the globe is that tropical regions are a lot, have a lot more species than temperate regions. And there's a lot of possible drivers for that pattern. But one of the possible hypotheses is that these infectious diseases or more generally biotic interactions. So that's just any sort of interaction between living things may be causing there to be more species in the tropics.Saintsing: Okay. So you mentioned the Red Queen hypothesis. What is, what is that, why is it called that?Visher: So the Red Queen hypothesis actually comes from Lewis Carroll's Alison Wonderland, and there's this one quote that's in all of the red queen hypothesis papers. And it says it takes all of the running. You can do just to stay in the same place. So that name was the Red Queen hypothesis. That name was actually originally used to describe some patterns in macro evolution. So macro evolution is the study of evolution over millions and millions of years. So pass the dinosaurs through the fish through when things were just single celled organisms, kind of macro evolution is concerned with those patterns, right? And so the Red Queen hypothesis, that name was originally used to try to explain why species went extinct. But later on in the 1980s, the name was kind of co-opted by people studying infectious diseases and parasites to explain why organisms or species more generally have evolved sexual reproduction rather than just clonal reproductionSaintsing: And clonal reproduction is asexual.Visher: Yeah. So clonal reproduction is just that you make an exact copy of yourself. And so all your offspring are just exactly you. So when we think about natural selection, kind of one of the key tenants is that the point of natural selection kind of what it works on is your reproductive fitness. So your ability to get your genes into the next generation.Saintsing: And so ideally you would just want exactly your genes.Visher: Exactly. So if you're clinical, you're getting a hundred percent of your genes into the next generation, but if you're a sec, if you're sexually reproducing, then only 50% of your genes are getting into each offspring that you make. So that shouldn't be a good thing. No, it shouldn't. Um, so there was a bunch of kind of funny paper titles. Um, one of them I remember is called "Why have sex?" And it's trying, they tried to explain why you would ever want to do that. And so one of the key reasons that you might want to have sexual reproduction is to be able to get your genes into the next generation in different combinations. So rather than having me with brown hair and hazel eyes, maybe for some reason next generation, it would be really bad for my offspring to have hazel eyes, but they still want to have brown hair. And so through sexual reproduction, I could possibly make some offspring with brown eyes and Brown hair.Saintsing: So sexual reproduction is like taking whatever you have right now, throwing it all against the wall and seeing what sticks.Visher: Yeah. Well, throwing it in with your mate’s genes and see what sticks. Exactly. Yeah. Yeah. So you're just mixing it up, kind of try and get different couple of different combinations and hopefully some of those combinations will be better at the future environment than the exact clone of would be. And so one of the big questions there was what sorts of environments make it so that you really want to mix up your genes that way, because a lot of kind of climate change or seasonal change that happens fairly slowly,Saintsing: Well, except now, right? With climate change.Visher: So, I mean, nowadays it actually would probably be really good to be able to switch up your genes very quickly, as fast as you can to keep up with climate change. But historically that hasn't yet. But historically that hasn't always been the case and climate change still is often happening over multiple generations of an organism or not of an organism, multiple generations of a species. And also it tends to be more directional. So that means it's, Oh, it's getting hotter for a long time or it's getting colder for a long time. And sexual selection can only really be selected for an a population if kind of the direction of the selection is changing every single generation. So if one generation it's good for me to have Brown eyes, that must mean that the next generation it's good for me to have hazel eyes and then brown eyes again, and then hazel eyes again. And there's not a lot of things in kind of abiotic. So your temperature, your precipitation, there's not a lot of things in those sorts of selection, selective pressures that change the direction of their selection, every single generation. And so the main thing that people realized might be changing the direction of its selection, every generation where infectious diseases or pests or parasites more generally, where if you have a virus that's specifically of involved to infect a certain genotype, then being able to change your genotype, every generation will allow for you to escape from that virus because that virus will be trying to evolve, to match whatever genotype is most common in the population. And so if you're clonal, it's really easy for a virus to keep up with the clonal population because viruses and bacteria have much shorter generation times than humans or plants. So a virus will have hundreds and thousands of generations to try to adapt in just one human generation, right? So one way that plants and animals host species can keep up with viral evolution is to be able to sexually recombine their genes to make new combinations. And so that means that whenever the host reproducing, it has a whole new set of genes for the virus to try to catch up to again.Saintsing: Okay. So viruses are very important for maintaining genetic diversity that we see across the world. And then going back, you also said that viruses play a role in shaping genetic diversity across the world. Differences in species diversity actually is what you said. Across the world. And can you tell us a little bit more about that too?Visher: Yeah. So one of the patterns that we've seen in nature for a really long time now is that there are way more species in tropical regions than temperate regions. So tropical regions are everything around the equator and temperate regions are the things closer to your North and South poles. And so there's way more species there in the tropics. And there's been a ton of hypotheses for why this might be the reason. So one hypothesis is just that climate has been a lot more stable there. Another hypothesis is that they're just warmer and maybe get more sunlight. And so there's just more energy and resources in the tropics, but another really promising hypothesis is that biotic interactions. So again, interactions between living things are what actually drives this higher diversity in the tropics. So we think that if biotic interactions are stronger or more specialized in the tropics, then that means that there's a advantage to being rare. So one of the big kind of areas that this hypothesis is used is to explain tree diversity. So why do tropical rainforests have so many different species of trees? I mean, this is called the Jansen Connell hypothesis, but one of the reasons that we think that they have so many species of trees is that if biotic interactions are really strong in the tropics, then if a seed lands really close to a seed of a tree in its species, then it will have a lot of negative fitness consequences. So whatever insect herbivores are on that tree might come and eat it. If there's any fungus on the tree of it, same species that it might come and eat it again. And so trees really don't want to be near trees of their same species, which means that kind of rarer trees. So trees where there's just fewer of their same species around have an advantage. And so whole forest ecosystems are much more diverse.Saintsing: So species maintain rarity. So you're saying viruses drive that, but is that just kind of like a consequence of what you were saying about trying to have this genetic diversity to respond to viruses that as viruses become more intense, there becomes more intense pressure from these viruses that ultimately you're just, speciated, you're actually becoming distinct species in terms of how genetically diverse you're becoming.Visher: So I think there's a difference in, well, sometimes there's a difference in our hypothesis between what driving speciation. So making diversity and what's maintaining diversity that already exists. So I think a fair number of the hypotheses that are trying to explain tropical species diversity have more to do with the maintenance of that diversity than the generation of that diversity. And so for things like the Jansen Connell hypothesis, so that's again just saying why trees that are rare can have an advantage in a forest because they can escape from pests and parasites that specialize on them. So it's taking those species pairs as already existing and trying to just explain why some of them are more competitive than others rather than necessarily explaining why they are speaciating or creating diversity in the first place.Saintsing: I see. So it's explaining why we would continue to have diversity in the tropics, but not necessarily how we got the diversity in the first place.Visher: There's other hypotheses for that.Saintsing: Right. So you're not arguing that viruses or potentially viruses played a role, but when you talk about viruses and diversity in the tropics, you're more talking about the maintenance of diversity. Yes, I see. Okay. Well, cool. So viruses are really important to evolution. Yeah, they are. This is just a reminder that I'm speaking with Elisa, Visher from the department of integrative biology. How do you actually study these viruses?Visher: So I personally use a method called experimental evolution. And so that's actually one of the reasons that I really like viruses as a study system is because they evolve so quickly. So what I do in experimental evolution is I take populations into the lab. So my particular model system is a moth and baculovirus model system. So it's just a moth, it's the Indian meal moths. So if you've ever had moths that have invaded your pantry before, eat all your flour, it's that one. So what we do in our lab is we have pots of those moths in our lab and we have vials of viruses and we kind of play at, we play at being God, actually an experiment evolution. We basically set up populations with some sort of, if we want to ask some sort of question, we set up populations of mods and viruses under some different environmental condition. And then we see how they evolve to meet that condition.Saintsing: I see. Wow. Does it make you feel really powerful?Visher: Yeah, I really like it. I really like it as a method because you get to have the reality of actually using a living biological thing. So a lot of people in my lab actually are just math petitions. So they do all of their work on their computers and on paper using numbers or really at their level, a lot of letters, but they don't, they can talk about why things might evolve, but they can't prove it in a biological system. I guess.Saintsing: There's math, but there's no driving process?Visher: Yeah. Yes. And then you need, yeah, there's math and it could explain what you might expect to evolve and then you have to kind of prove it.Saintsing: Right.Visher: In an actual living thing. And so I like to say that I do math with malls because I can basically take those predictions that the mathematicians make about whether an environmental condition. So say whether your population is genetically diverse or not. So I can take that math. And then I can ask what a virus that's evolving in a genetically homogenous system. So there's only one genotype everything's clonal evolve differently than a virus that's evolving in a genetically diverse host population. And so I take that math. I find my moths, I make one population that's genetically diverse. I make another population. That's just all one genotype. And then I can put my virus into those two different populations and see how it evolves in response. So what I do kind of sits between the math and then also more kind of the more realistic field work. So experimental evolution still has a level of non-reality to it because we're kind of making up these environmental conditions and we're putting things in a lab and we're just trying to make everything except our exact question that we're asking as consistent as possible. And so that's where it has a bit more power sometimes than field work because in field work, you might have a question about how host genetic diversity affects how a virus evolves, but any sort of system that you find in the field. So if you could just go out into nature or to a farm, there's going to be a ton more variables involved between non genetically diverse populations and genetically diverse populations. So there might be differences in temperature. There might be a differences in precipitation. You might have to look at entirely different species to be able to compare, but with experimental evolution in the lab, I can basically isolate my one variable of interest and test only that one.Saintsing: Okay. So now you do experimental evolution work on moths. Was that just kind of a project you came to here? Or, I mean, how did you end up working on this virus and this moth?Visher: Yeah, so I've done experimental evolution for a bit. I did a little bit in my undergraduate, but where I actually started was in biological anthropology. So I like many...Saintsing: So you did use to study humans?Visher: I did use to study humans and I've studied human and I don't hate humans in theory. I will always keep some sort of human bent to my work. I'm just right now, I'm studying very things, very far removed, very basic science, right. And so I like many college freshmen originally wanted to be a doctor. I think it's, it's, it's obviously it's something that has a lot of career stability. It's something that kind of allows you to do a bit of science, but a little bit through my freshman year, I started actually shadowing doctors and I realized that it didn't allow that being in medicine as a MD probably wouldn't allow me to kind of explore questions the way that I wanted to. So I had a, I guess, crisis and I was looking to see what else I might want to do. And so I don't remember exactly when I just remember being in my bed in my freshmen dorm and being like, what do I want to do? And remembering this time in high school, where I was going to the California Academy of Sciences with my family, and I had recently seen on the news that, Ardi was a skeleton that was found actually by a professor here at Berkeley, and already was at that point, the earliest hominid fossil that had ever been discovered. And I was really excited by this. I was reading all the news and I kept on having all these questions about why humans evolved. And I think that experience was actually the first time that I was really exposed to real science because as I was trying to figure out, well, why did Ardi evolve? Like I was trying to look at it like I was doing my high school science classes, clearly the answer should be in a textbook. Right. Um, and I found that there was no answer. That's what the scientists were doing was actually trying to find these answers. And for some reason, as I was looking back on this, my freshman year, this idea that I could be involved in trying to find the answers in being involved in like a very creative process, honestly, that seemed really exciting to me. So I joined a biological anthropology lab that summer. In that lab, I wasn't working on human evolution. I was working on primate evolution. What, what projects was I doing? I was, my first project was looking at chimpanzee poop and trying to kind of use it to track chimpanzees around this natural national forest. I never, no, I never saw chimpanzee. I just got vials of it's poop. And then I played with it in the lab.Saintsing: Wait, were you in Africa?Visher: No.Saintsing: Oh.Visher: No, just vials of poop in the freezer pulled them out.Saintsing: Well, you got to start somewhere.Visher: Yeah. Tried to get the DNA out of it and that entire project failed, but I stuck with it even though I didn't get any data from that project. I really liked the process, I guess. So I continued in biological anthropology for a couple years. And in my classes I started also learning about more recent human genetic evolution and how more recent human genetic evolution was also implicated in kind of genetic diseases of humans and kind of differences in how different populations dealt with infectious diseases. And that seemed really interesting to me. So at that point I started taking more classes in evolutionary medicine and at one point I was like, so I've been learning all of this from the human side. I can either do a lot of genetics in the lab, or I can, I guess, try to like dig up human fossils in the, in the field, or I'm also really interested in how evolution impacts infectious diseases. So I decided to join a lab that would allow me to look at how evolution impacts infectious diseases from the viruses side, rather than just the human immune system side. So I joined another lab my junior year and in that lab was actually where I got started with experimental evolution. So that lab was working with viruses and bacteria. So they were working with bacteria phage, which is a type of virus that infects and kills bacteria. And that lab, I started doing experimental evolution on these very kind of like basic science, theoretical principles. And I really loved it. I really loved the methods of experimental evolution. I really liked how it seems like I could be very creative with what questions I came up with and also kind of designing experiments to try to test them. And so I decided that I wanted to stay on the infectious disease side of things. Um, and then once I graduated college, I didn't want to go straight to graduate school. I kind of had decided I'd made my final decision that I wanted to do infectious diseases kind of towards the end of things a little bit past when I would have wanted to start applying to graduate school. Right. And I also just wanted a little bit more experience and emotional maturity, I guess, before going into graduate school. So I applied to be a research technician and I joined a lab at University of Michigan that was studying flu evolution because I also wanted to explore what more applied infectious disease evolution looked like since I had done very basic science, infectious disease evolution. And so I worked with flu for two years, and then I started applying to graduate school and came here to Berkeley.Saintsing: How'd you pick Berkeley?Visher: Oh dear, should I say this? So I made some interesting decisions, I'll say applying to graduate school. Um, so I started emailing a lot of professors and getting in contact with them. And I think at this point I had decided that I wanted to go back into more basic science, infectious disease evolution. So I realized that I really liked being the one to come up with these more theoretical questions rather than trying to explain actual applied infectious disease systems. And so, as I was looking around at different graduate schools, my current PI Mike Boots had actually just been hired at Berkeley. So I had been checking Berkeley's website a couple of times because I'm from California, it's a very good department. I was like, well, this would be a great school. If it has someone there for me, when the first couple of times it didn't have anyone here for me, but then kind of all at once, both Mike and Brit, Brit Koskella, were hired and suddenly Berkeley seemed like a really great option. And so when I was reading about Mike Boots's work, I really liked kind of the type of question he was asking the fact that the lab looked at these very theoretical infectious disease questions. And I ended up Skyping with him. I really liked the model system. I like the moths. There are, they're a pretty good system. You don't feel as bad about killing them as you do with mice. You can see them a little bit better than you can see bacteria and bacteria phage. So by the time applications came around, I actually only applied to Mike Boots, his lab, which was the choice. I'm not sure I would recommend it broadly,Saintsing: But being in touch with them, you felt confident.Visher: Yeah. I'd been in touch with him for quite a bit at this point. And I personally know that I'm very stubborn and my mother has told me that I'm very stubborn. And at that point I just really wanted to come to the Boot's lab. And I figured if it didn't work out the first year, I would make more sensible decisions. The second year I had applied to more labs and luckily I got in and I came here.Saintsing: That sounds like a good way to get here. And now you're here and you're investigating experimental evolution. And you’re in your third year,Visher: I'm in my third year. Yes.Saintsing: And, do you have plans for life after graduate school?Visher: What happens afterwards. Um, I will say I have a lot of plans just cause I'm in, I am at the type of person who will plan out three 10 year plans and then make rapid decisions between them. But yeah, so I think I personally really want to stay in academia. I want to stay as a research professor. Um, of course that's a very tough career path to get into. So, you know, I might have to make some other choices, but right now I'm definitely, you know, trying to get my PhD in the next two to three years go on to do a postdoc, maybe two, maybe more, I don't know,Saintsing: Just because that's the way it works in the job market?Visher: Yeah. It's, I mean, it's the way it works. And then I also, I think there is a lot of value in exposing yourself to different lab systems, to different lab cultures, to like different both intellectual cultures. And also I guess more like, you know, mentorship and those sorts of cultures that you can, I guess, create an individual identity for yourself as a researcher and be able to kind of combine the intellectual perspectives of a number of different groups to make your own research program. So I'm personally actually pretty excited about doing postdocs and kind of doing random things, learning new things, doing cool science.Saintsing: Yeah. Yeah, that sounds cool. And then after that you want to get an academic job, a tenure track professorship?Visher: Ideally. Yeah. We'll see how that goes.Saintsing: Well, I wish you the best of luck in that pursuit. Uh we're about out of time, usually, uh, at the end of the program, we offer the guest time to make any points about, um, their science or social issues or anything you'd like to talk about. So are there any statements you'd like to leave the audience with?Visher: Let's see. Oh, I gues I know the statement I'll leave the audience with. So I think coming from an anthropology background, I did a lot of social sciences and I also kind of studied a fair bit in medical anthropology. And I think we often think that our biology, that biology, that we study is really apolitical and divorced from kind of social issues. But I would like to say that infectious diseases are inherently political. And a lot of the pressures that you see from infectious diseases across the world are really unevenly, distributed along axes of power. You see things like huge infectious disease burdens in parts of Africa and parts of Southeast Asia. You see that infectious diseases are worse with political instability, with emerging infectious diseases like HIV. You found, you see that we had an epidemic that reached across the globe and infected millions of people before political entities did anything about it because it was infecting people who were already marginalized by society. So I think in my personal work, even though I am very much on the theoretical end of these things, scientists need to pay attention to society, to humans, to marginalized people, and actually integrate them into what we do and kind of integrate the learnings of social sciences into our biological science.Saintsing: Okay. So we can't avoid politics and science.Visher: We cannot avoid politics in science or medicine.Saintsing: Right, yeah. That's an excellent point. Thank you so much for being here, Elisa. I am Andrew Saintsing and I've been speaking with Elisa Visher. She's told us about her work and experimental evolution to understand how viruses can, uh, lead to genetic diversity in populations and maintain species diversity in the world. Tune in, in two weeks for the next episode of The Graduates.
2/26/2020

Nick Spano

Erik Sathe: You're tuned in to 90.7 FM KALX Berkeley. My name is Erik Sathe and this is The Graduates, the interview talk show where we talk to UC graduate students about their work here on campus and around the world today, I'm joined by Nick Spano from the department of integrative biology, who studies conservation, paleo biology. How's it going, Nick?Nick Spano: Pretty great. Erik.Sathe: Good. I'm glad to hear it. So how did you first get into research?Spano: Yeah, I first got into research through really just keeping my nose to the grindstone with classes and really getting involved in that and really finding that as kind of a fun pursuit to learn these things in classes. And what happened was I took an earth history class during undergrad, and I had talked with the professor and I told him, Hey, I am interested in paleo stuff. And this has been earth history class. Are there any opportunities for me to do something like that? And he said, sure, yeah, I run a research facility here on campus. You want to come check it out sometime? And I said, yeah, that sounds great. And so he invited me over to check out this facility and the facility itself is called the large lakes in observatory. And it is a institution at the university of Minnesota Duluth, which is right on the Western tip of Lake superior and being right on the tip of Lake superior. The idea is, okay, this is the biggest Lake in the world. We can effectively treat it as an ocean. And so the people who work there are mainly trained in oceanography, study things about ocean physics, ocean chemistry, plankton, and so forth. But his background was in paleoclimatology and being able to tell how climate has changed through time through sediment records that people have pulled up from the ocean floor. And so he just showed me around this building and at the end of it, he said, yeah, how does it look? How does it sound? I said, yeah, this is all really cool. And he said, great, do you want a job? I said, yes, please. And yeah, that was a really fortunate start for how I got into research. Yeah. It sounds very organic. And it was kind of following your own interests and just sort of happening across someone who could provide an opportunity for you. Yeah. So what can we learn about the climate through paleontology? Yeah, that is a really great question. So I would say the main thing that we can learn about climate through paleontology is a sense of scale about how bad climate change is today. And so, by saying bad, I mean, what is the rate at which climate change is happening? It's speed, it's magnitude. And so there are things for example, where we can look at, okay, climate is warming today has climate warmed in the past. And by looking at the paleontological record, we can say, yes, climate has warmed in the past and we can get into the question of, okay, how quickly did things warm in the past and how quickly are things warming today and how does that compare? And there are a lot of very stark things that pop out from that. And so, for example, when we look at a very extreme warming event that has occurred in earth's history that we see recorded in the history of life. At that time, the paleontological record, it is an event called the Paleocene Eocene, thermal maximum. And this happened about 55 million years ago. And what we see happening then is a change to primates at the time, living in places where they'd never lived before to a lot of species in the ocean becoming extinct. And the rate of warming of that event was something that is the highest we've seen in the past, at least 65 million years. And for the carbon dioxide that was put into the atmosphere and caused a warming at that time, the rate at which that carbon dioxide increase causing that warming compared to the rate of carbon dioxide increase we're seeing right now is tenfold. So we are pumping out CO2 at a rate that is 10 times faster than the fastest rate in the past 65 million years. So that's one thing. And for more recent paleontological history, we can look at the past about two and a half million years of the ice ages and see these trends from things that are really cold during the peak of an ice age, to relatively warm, similar, to more recent temperatures. And we can get a sense for how climate can change on scales and timeframes that are more similar to what we have effectively grown up with that is looking at communities and the paleontological record that include things like wooly mammoths and sabertooth cats and mastodons, but also include things like moose and Canada, geese and raccoons and black bears, and really get a sense for how climate change has affected those animals and those plant communities that are still around today, or at least very similar to those around today and see what happened when climate change then.Sathe: Okay. And so it seems like you do sort of field paleontology. Do you go out and do field work yourself?Spano: Yeah, so I have only done a couple field related things in my research so far, my current research focuses on a experimental approach to testing a fossil that people use as a tool to get at environmental reconstructions. And what I'm doing now with the experimental work is to try it and see how good of a tool it really is. But the field work that I've done has included going to the Island of The Bahamas that is San Salvador Island. And this is the Island that Christopher Columbus first landed on in 1492. And what we were looking for there is evidence of how the ecological community had changed when those first Europeans arrived on the Island. And so that was a very cool experience to do some field work that involve Lake sediment, coring. And the idea with that is to take effectively a big plastic straw and put it into the middle of the Lake and just like a straw in your milkshake, you put your finger on top of it to plug it, and then you pull it up and you pull stuff out of it. And what we do that is not delicious ice cream and milk is pull the mud out from the bottom of the Lake. And the idea with that is we have this tube and at the bottom of the tube, we have the oldest stuff in the mud. And at the top of the tube, we have the youngest stuff in the mud. And so we can go through time and look at how the environment has been changing in terms of water quality, in terms of plants that were living around that Lake and sprinkling their pollen into the Lake. And the pollen are very useful because they preserve really well. And they are very diagnostic to be able to tell what kinds of plants were around the community. And so you can get this whole really interesting environmental picture of what was going on through time. And especially with the case of lakes, because lakes are relatively common across the landscape in a lot of different places, you can get a lot of interesting environmental history. For example, with Christopher Columbus, how things happen there, how different domesticated plants have spread around the world and so forth. So that's one example of field work that I've done. Some other field work that I've done earlier in my graduate career was some work that I did in Africa. So I got to go to a whirlwind tour spending two weeks total in Kenya, Botswana and Mozambique. And that was pretty wild. And yeah, that involved collecting some dung samples to try to get at some ecology of large animals and collect.Sathe: Dung samples of what?Spano: Yeah. So I was collecting dung samples from pretty much anything I could find. Okay. Elephants and zebra and some antelope. And there's a lot of poop lying around in some places of the Bush in Africa. It turns out. So how did you know what kind of poop you got? Yeah. So I had a, both a guidebook that I had with me and a local guide, especially when I was in Mozambique. Crews were really helpful in being able to identify who's poo was who's for elephant poo in particular. It is very easy to identify because it's about the size on the ground as a dinner plate. And each ball of poo is about the size of your fist. And the interesting thing about elephant poo in particular is that most of it goes pretty much undigested. And so about 75% of the dry mass of an elephant poo is just grass and other plant material that just pass right through.Sathe: And so how did you use these samples in your research?Spano: Yeah, so I use them to try to get at getting back to what I was talking about earlier with this experimental work that I'm doing now is trying to see if the poo had this dung, fungus that I'm interested in. And so I'm interested in a dung fungus because we find spores of this young fungus in the sediment records at Washington lakes that washed into swamps that wash into wet patches on Meadows and so forth. And people in the paleontology community have been using the spores. Those are the little reproductive cells of these fungi as an indicator for how many animals were walking around landscape, especially large mammalian herbivores. And what people have found through looking at these spores that are incorporated into sediment records. There's some interesting things about being able to time the extinction of a lot of ice age animals. So the idea is less spores means less poo means less wooly mammoths, for example, and associated with that. People have been able to tie those changes in the amount of spores in a given record and those extinctions to cascading ecological consequences. So one idea for North AmErika, as an example is that when we lost things like wooly mammoths and mastodons and giant ground slots that were about the size of an elephant, which is pretty wild slough, the size of the slots, the size of an elephant, some of them ones in South AmErika were actually about one and a half times the size of an elephant. And we have some reason to believe or suggest from their pelvic bones that they could have supported their weight on their hind legs, at least for some time. So it's pretty wild.Sathe: So, these things probably weren't hanging upside down and trees like the fluff that we know today?Spano: Probably not as far as we know, but yeah, so people have been able to find that based on the timing of these extinctions inferred from the spores of the stung fungus in these records, you see really interesting changes in the rest of the environment that are happening, where you see an increase in the amount of pollen from Ash trees that takes off right at the same time. And you see a increasing the amount of tiny itty bitty little pieces of charcoal that wash in these sentiment records as well. And people use the charcoal to infer what the fire patterns look like on landscape through time. And what we see happening is this landscape ecosystem, radical change that was occurring in the context of warming that happened as we were coming out of the most recent ice age. And along with the warming, we see these ecological changes that were caused by the loss of these giant herbivores. And so that has some pretty big implications for the last giant or Varsa. We have left today, for example, African elephants and how they change the vegetation in savannas and grasslands or hippos and how they can act as what's called ecosystem engineers in Subsaharan Africa as well, and what it means to conserve those animals and conserve those landscapes that they literally create, especially for being able to support a really big Safari industry and tourism and the intrinsic value of those animals themselves tooSathe: That's amazing. So it's really interesting that you're sort of using a resource that people might not think of as very valuable, you know, dung samples to make very well-informed assumptions or guesses about what these ecosystems were like in the past.Spano: Yeah. And so it's something that, it seems like the last place you might look for information like that. And I think that's a pretty fun pattern that pops up a lot of times in ecology and science and natural history is somebody is curious about something in its own. Right. And it turns out to be important for all sorts of other things.Sathe: Are you pretty unique in studying dung samples in paleontology and conservation biology or is the sort of a common thing?Spano: I'd say, I know some people who do that kind of work, but we are few and far between.Sathe: Makes sense. Yeah.Spano: Yeah. It's not the most charismatic of approaches to these things, but it can tell you a lot of really interesting information.Sathe: Definitely. So you said you did feel to work in Africa and I'm wondering if you have any crazy stories from your experience.Spano: Yeah. I have at least one crazy story, which is the first country that I visited. And the first place that I visited on my trip to Africa was a field site in Kenya. And what I was interested in doing first day was to go to a bunch of watering holes that were at this research station in Kenya and see what kinds of animals were around the watering holes. Maybe get a sense of where they were pooping and to really think of that as a comparison to wear animals during the most recent ice age. And before that might've been concentrating around lakes that we now use for the sediment records and the stung fungus. So we get up to this watering hole and there is a herd of elephants that's drinking right at the edge of the watering hole. And it's beautiful and their mom, elephants and auntie elephants and baby elephants. And there's a bunch of baby elephants, which is great. But next thing we know, and I have a photo of this very moment. You see mom, elephants raising their ears up, pointing them at us, trying to look big and they start walking towards us and speeding up and we realize, Oh my gosh. So we are booking it out of there trying to get away from this herd of elephants. And we're driving around trying to get away from the watering hole. And we come around this Bush and there was a mama elephant who bellows at us. And she is probably I'd say no more than six feet away from trampling us. So that was my first day of field work in Africa. It's a good start. Yeah. And I'm still here. I'm so glad to hear it. Yeah. Yeah. Me too.Sathe: You have talked a little bit about the, the coring method for the samples that you take. What's sort of the timescale on these cores. How far back can you go?Spano: Yeah, that's a great question. So it depends on the course itself. In some cases we can get back up to the scale of millions of years in some settings, especially cases where the Lake bed itself has long since dried up, but people take a drilling rig just like people use for oil rigs, but drill into these dried up Lake sediments and get back down very, very, very far back in time. And especially with big lakes and deep lakes, we can get to these scales of hundreds of thousands, if not millions of years. And really cool thing that happens with some lakes is that based on the seasonal changes in what kind of plankton are present in the Lake and how the water chemistry is changing in the Lake throughout a year, you have these layers that form in the Lake sediments that correspond to one year each just like tree rings. And so we can get down to that level of being able to tell a year by year how this environment has been changing through time.Sathe: That's amazing. So you're from Minnesota, I'm from Minnesota, Minnesota has over 10,000 lakes.Spano: You betcha.Sathe: Have you done any coring in Minnesota?Spano: I have, yes. So there are quite a few lakes around the twin cities area and a lot of work that people at the university of Minnesota are really interested in is this approach to try to use these techniques from paleontology and geology of Lake sediment, coring to get at more recent history and more recent environmental change that's been going on in Minnesota. And so for example, people have been looking at the history of plant domestication within native American cultures and how the signal of that is preserved in these like sediment records and how pollution can be recorded by heavy metals and other things at Washington Lake sediment records, and even the development of suburbs and urbanization can be observed by the different things that Washington to these lakes. And that's a really cool thing about it is we can use these techniques to get at all of that information and have those records and have those archives and really measure the effects of say both how bad pollution has been in the past and see conversely how different policies had been enacted to, to lessen that pollution have really made a difference.Sathe: Okay. So we've been talking about North America now and sort of the paleontology conservation Paleobiology that you've been doing here a little bit. I'd like to hear a little bit more about the landscape of North America and sort of what the ecosystem was like at this time that you're studying.Spano: Well, I'm always happy to chat about that. And so for Minnesota, in particular, as many people know, most of it was covered in ice sheet that was in some places up to a mile thick. And so a lot of Minnesota is Rocky from rocks that washed out from the melting ice sheet, but there is a chunk of Minnesota that was actually missed by the waves of ice sheets that have been coming across to the North American landscape for the past couple million years. And so that is very ecologically interesting. It's called the Driftless Area because we see both a less flat landscape in that part of the world and also a relative Leigh higher number of different species, especially of amphibians and reptiles in that area. And the idea of that was, well, they weren't hit by the glacier, so to speak. And so they were able to hang out there while these changes were happening, which is really cool, but more locally within the Bay Area. I think there's some really cool things going on with the landscape and who is around and what was happening, where if we go back to the peak of the most recent ice age, if you're going to build giant ice sheets and glaciers that characterize the ice ages, as we know them, all that ice has to come from somewhere. And so that somewhere is the oceans. And when all of that ocean water was locked up in these ice sheets, it dropped down sea level significantly such that Indonesia, as we know it today was mainly just a large landmass connected to the rest of Asia and in the Bay area, we see not the San Francisco Bay, but we see really the San Francisco Valley, which the Sacramento river was cutting out. And if you look out on a clear day, past the Golden Gate, you can see the Fairlawn islands right on the horizon. And during the peak of the most recent ice age, the California coast extended 20 miles out all the way to those islands. Wow. And so we had this giant plane with grasses and all of this really cool stuff going on in California. And at that time we had things like mammoths and mastodons and giant ground slots and even camels that were living in the Bay Area. For example, when the downtown Berkeley Bart station was being built, people were pulling camel bones out from the rocks and the sediment that was there. So they were walking around Shattuck. And we also see things like a, what is called the American line, which is a cousin to African lions, but looked pretty much the same as African lions, as far as we can tell, but about 30% bigger. And we saw things like caribou and moose and deer and bears and all these other animals that are still around today. But then with this whole other half of the cast that is now extinct, which is pretty wild to think about.Sathe: Why do we think that those other half of the cast is extinct?Spano: Yeah, that is the killer question that people have been trying to get at for the past 60 years now. And so one of the first people to really try to get at this and the reason for why we see so few large animals today compared to the ice ages is this guy, Paul Martin, who he was a paleontologist at the university of Arizona. And the story goes that he was a PhD student and he got his PhD studying peat and swamps and coring them and getting at the paleontology of that. And he finished up with it and he was trying to figure out what he was going to do next. And he was just curious and open on a weekend. And he thought, you know, people have been playing around with this radioactive carbon dating method on a lot of archeological sites. And ice age paleontology size. I wonder if we look at those dates, if we see any patterns pop up and what he saw was a very clear pattern of which animals became extinct, namely disproportionately large animals, and that the timing of those extinctions really seem to match up really well with the first appearance of humans in different areas. And so, for example, when we look at places like Europe, we see a wave of extinctions around 40 to 50,000 years ago, right around the same time that humans show up. When we look at North America, wave extinctions from roughly 13 to 10,000 years ago, right around the same time human showed up South America, same thing about 14, 13, 12,000 years ago to 10,000 years ago, right around the same time human showed up. And so we thought, huh, that is quite the coincidence. I wonder what's going on. And so he proposed this idea that people came in at, if not through, what's called the Blitzkrieg model of people just wiping out the animals as quickly as possible. Maybe through some combination of habitat modification and hunting and other human pressures. Humans had caused these extinctions that we think about human caused extinction today, but maybe this was even happening tens of thousands of years ago. And so he proposed this idea and the people in the paleoclimatology community kind of looked at it and said, wait, you're trying to tell me that a bunch of people with sticks and spheres came in and wiped out entire species that had been living in these areas for tens of millions of years before that. No, that's crazy. We know that things were getting warmer when these extinctions were happening too. And so it was probably global warming that caused these ice age animals so disappear. And so there had been this back and forth debate and battle in science over whether it was humans that caused the extinction or climate change that caused the extinction and people have been butting heads about it for the longest time. And now we're finally getting into a space in paleontology where we can say, well, wait, why not both? And so now people are getting at the potential for a synergistic effect. That is when you add climate change with human impacts together, you get this multiplication of the two that causes species to become extinct. People are really with refinements in how radioactive carbon dating works have been getting at more precise stories of who became extinct when, how quickly those extinctions happened, how they occurred in the context of how climate was changing and how human populations might have been increasing at different times. And so we're getting a much more interesting story. That's much more complicated, but at the same time, much more comparable to what we see today with a whole combination of factors that is causing population declines. And the implications for modern conservation biology are huge to say that this has happened before. It's entirely possible that this couldn't happen again.Sathe: Do you have a favorite large animal that you sort of wish was still around?Spano: Yeah. Oh, well, that's kind of a two part question. I'll start with the favorite animal in paleontology. And my go-to at this point is what's called the Colombian mammoth. And so it was a cousin of wooly mammoth. But interestingly, when we think of a Woolly Mammoths we tend to think of really, really, really cold places. But if we look at where Colombian mammoth fossils have been found, we see them in places like Arizona and New Mexico and Texas and Mexico proper. And even during the peak of the most recent ice age, those places were colder than they are now, but not ice sheets, Tundra cold. And the really cool thing about that is that we infer that Colombian mammoths were probably not that woolly. And they were probably very similar in their ecology and their behaviors to living elephants that live in warmer areas. And so the Colombian mammoth exemplifies this idea that, okay, maybe not all, mammas have to be Woolly or associated with very cold conditions and can be comparable conceptually to elephants that we think about today. And so the second part of that question about whether I wish they were still around today gets at a very interesting field of animal ethics and conservation. That is the idea of de-extinction and people have been talking for some time about kind of a Jurassic Park style story of, well, what if we could bring woolly mammoth back? And then the question again, related to Jurassic Park is, well, should we bring them back? And although, I love ice age giant animals and thinking about them and learning about them. I think that if we were to really bring back a Colombian mammoth from the perspective of animal ethics, if they are so comparable to elephants, as we know them, I mean, elephants are very social and sociable animals. And so those first Colombian Mammoths, I mean, thinking if this was actually a real thing, might be really sad and whether we should really pump all that money into the genetic engineering and trying to get all that down, when there are much more pressing conservation issues, if we were to sell it as a conservation thing to bring back, these mammoths is something that I don't think it was very warranted. And so I do love seeing large animals still in the world and being able to experience a world in which that's part of the story of how life works and how the universe does things. But yeah, whether I would actually want that back is a very tough question.Sathe: Definitely. So that's about all we have time for. Is there anything else you want to say nothing?Spano: Yeah, not that I can think of right now other than, yeah. Just thank you for having me here.Sathe: Of course. Thanks for coming in. You're listening to the graduates on KALX Berkeley. My name is Erik Sathe and I was joined today on the show by Nick Spano, from the department of integrative biology, talking about his research on a conservation paleo biology. We will be back in two weeks.
1/28/2020

Mattina Alonge

Andrew Saintsing: Hi, you're tuned into 90.7 FM KALX Berkeley. I'm Andrew Saintsing. And this isThe Graduates, the interview talk show where we speak to UC Berkeley graduatestudents about their work here on campus and around the world. Today, I'm joined byMattina Alonge from the Department of Integrative Biology and also a fellow host ofThe Graduates.Mattina Alonge: Hey, Andrew.Saintsing: It's so great to have you here, Mattina. We're really excited to hear a couple moreinterviews produced by you this semester.Alonge: That's the right way to put that.Saintsing: So stay tuned. So Mattina, how are you doing?Alonge: I'm doing good. I'm great.Saintsing: Cool, cool. Unlike all of the other hosts, current hosts of the graduates, you do not study biomechanics.Alonge: That's true. Yeah. I’m the one stand-alone non-biomechanics nerd.Saintsing: What do you study? So, I would also say I'm a physiologist. So do you, would you callyourself a physiologist or?Alonge: Why, why do we have to find a label?Saintsing: Yeah, that's a, that's a good point. Good point. Science is so interdisciplinary, right? Wedon't need to be labeled and sequestered.Alonge: I think that' a really hard question and people ask it a lot of anyone who is involved inscience, but I think I would call myself an eco-physiologist.Saintsing: Okay, cool. So you'e interested in how organisms are relating to their environment andhow energy is moving. Not just through an organism, but through the ecosystem as awhole.Alonge: Yeah, exactly.Saintsing: What, what do you study in that? You, you look at birds?Alonge: And bats, yeah. Flying things. I love things that fly. Yeah. So I guess in general, myquestions seem to centralize around this idea that every animal is juggling a lot ofenergetic demands, just like people. So we have to make conscious and strategicdecisions about what we choose to prioritize at any moment in time and animals do thesame thing. And a lot of that is impacted by the particular environment that they're in.So in terms of birds and bats, they're interesting because they fly obviously, but flight isa pretty costly activity, especially for mammals who also have added demands in termsof reproductive activities like pregnancy and lactation, which are also reallyenergetically, demanding,Saintsing: What do you mean? Birds have to create their offspring too. Right? I mean, but I guessit's all that they, they make an egg and then they just kind of are done with it.Alonge: Yeah. I mean, you shouldn't like diss on bird parents. They still put a lot of energy intoraising babies, but it's a little different, they don't have to carry around this extra weightand, you know, shuttle a lot of internal resources to their offspring and sort of like aninvestment that they make in this one little package. And then they drop it off and takecare of the package for a while, but they don't have to carry it around and feed itconstantly until it patches, I guess. But yeah.Saintsing: Okay. So you're looking at how they navigate those energetic demands and you have a,or your work is kind of focused on the reproductive aspect of their biology?Alonge: Yeah, exactly. Yeah. I guess because reproduction generally is a pretty costly activity forany animal, whether it's birds bats or any other species. So, and it's also reallyimportant, right. For the success of that species. Like every animal cares aboutmaximizing his fitness and reproduction is a key part of that. So, um, I think also if, youknow, if people are interested in conservation and things like that, um, understandinghow animals might prioritize reproduction or not prioritize reproduction at any momentin time can be really important with the changing environment. Right.Saintsing: Yeah. Okay. And so how do you study these questions? You're kind of looking athormones, right?Alonge: Yeah. So part of what I study is endocrinology or hormones. What is a hormone?Saintsing: What is a hormone?Alonge: So I guess, uh, the simplest do I, if I had to summarize it is it's, um, a little tiny moleculein your body that serves as a signal. Um, and it has to be transported from one part ofyour body to the other. So for example, there are a lot of hormones that are producedin your brain and get shuttled through your bloodstream, to other tissues in your body,uh, in terms of reproduction, that's typically things like your gonads. Um, so ovaries andtestes and, um, yeah, and they just basically tell other tissues what to do at any momentin time. And hormones are really cool because they'e fast acting. So for example, um, ifsomething gets stressed out, like, you know, if a clown snuck up behind you and tapsyou on the shoulder and turning around and scared you, then you would suddenlyrelease a lot of glucocorticoids, which are stress hormones. And that's what sort of givesyou that feeling of having to like run away or jump and your heart starts racing. And allof that, it's a really sort of like primitive response and hormones are a really primitivetype of molecule.Saintsing: Right. So anything that's multicellular theoretically might have hormones?Alonge: Hm. So I guess, uh, I don't know the answer to that question. Uh, I think that theydefinitely have been around, like, I know obviously a lot of early, early organisms, likeearly, early invertebrates had like the same hormonal pathways that we have now. Uh,so I assume that you need to have probably at least a bunch of cells and probably a fewdifferent types of tissues that are differentiated within an organism to actually havehormones function.Saintsing: Right. Yeah. It was, yeah. The way you said it, I just thought like, okay, you just have tohave like one single molecule be made somewhere and then pass to somewhere else.Alonge: Yeah. So, yeah, I guess like there's different types of, I mean, this is a tangent, weshouldn't go down. Hormones can be like released from your brain to another tissue inyour body. Um, and that's like a hormone functioning and then the traditional way, um,when you have like two cells that are signaling to each other and they're right next toeach other, you technically wouldn't call that a hormone because it';s not actuallytraveling to like a far enough location. So there's this certain like distance aspect ofendocrinology. That's important for calling something, a hormone, which is really weirdbut..Saintsing: Yeah, that's really interesting. So theoretically, you could have the same molecule passfrom a cell to its neighboring cell and not be a hormone and pass from a cell to a cell,like separated by your leg. It wouldn't be a hormone. Yeah. Weird. Okay. So then yousaid we share hormones with, did you say like invertebrates?Alonge: Yeah. Like a lot of our, um, very, I guess classical endocrine pathways that we have inour bodies. Um, and also birds and bats have the same ones too, uh, early in vertebrateshad the same thing. So it's like stress response. And that happens through a particularconnection between your brain and your pituitary gland and your adrenal. And that axis,uh, has existed for, you know, millions of years and has been relatively unchanged interms of the molecules involved. But the way it responds to the environment can differ.Saintsing: So, stress runs deep. Stress runs really deep. Yeah. Cuts deep. Okay. So are thereparticular hormones that you're looking at?Alonge: Uh, yeah. So I'm mainly interested in things related to regulating reproduction. So thereare a couple of key hormones in the brain, um, something called gonadotropin releasinghormone and gonadotrophin inhibitory hormone, and you might be able to deduce this,but one is sort of this on switch for reproduction. And the other one is an off switch andthey're really sensitive to aspects of, you know, an individual's condition, how well it'sdoing. Is it healthy? Is it stressed out? Is it sick? Um, but also sort of cues from theenvironment. So a time of year photo period, even things like food availability or wateravailability can turn reproduction on and off. And it usually happens through that sort ofon, off switch in the brain.Saintsing: Okay. So this hormone, uh, it tells the birds that they want to mate, basically.Alonge: Yeah, well like, yeah, basically promote the signals that say, okay, Hey, you're healthy.Everything's good. And the place that you live, it's a really good time to reproduce likeyeah. All of the on switches for reproduction get turned on.Saintsing: Right. And then, so they all right. So you're looking at this hormone in both birds andbats. And you'e, are these animals like gregarious? Do they hang out in likeAlonge: Gregarious? Wow. I'm going to like start incorporating that into my lingo.Saintsing: Yeah, definitely. I love that word.Alonge: So yeah, I would say they're actually very gregarious. So the birds that I study are zebrafinches and they naturally live in a colony they'e native to Australia. And so they'resuper social. They are happiest when they're in a group and they are also opportunisticbreeders. So I don't have to wait to do my experiments or, uh, yeah. Do you mindmeasurements at any particular time of year? They'll just breed whenever things aregood. And since they're, uh, th the birds that I study here and it captive colony, thateverything is pretty much good all the time. So you're constantly having babies, which isa really good opportunity for me as a grad student. Right.Saintsing: Yeah. Okay. So yeah. So these birds, theoretically, they're always around potentialmates and they could potentially mate at any point. Um, but you'e saying that in thewild, maybe natural cues would prevent them from me.Alonge: Yeah. So some of the main things that regulate reproduction for these birds in Australiaare, uh, either weather or food availability, which is super linked to one another, I guess.So typically if there's like a really, really dry season, and there's not a lot of food, theywill shut down their reproductive access. So there'll be a lot of that inhibitory hormonein their brain. And they won't be interested in reproducing, but they can turn it on reallyfast. So if food becomes available or if the weather becomes good and temperatures areideal, then they can reproduce again. So, yeah, but I actually, in terms of my work, I'mless interested in how they respond to their environment and more how they deal withmanaging or prioritizing reproduction when they encounter something unexpected, likea pathogen or getting sick.Saintsing: Oh, so you're making, or you look at birds that have gotten sick, or do you have like avirus that you're introducing into the colony or something?Alonge: Yeah, exactly. So, um, one of my projects is using something called lipopolysaccharide,which is not a virus, but it's just a part of a bacteria. Um, and the coolest thing about it isthat people who are experts in isolating, uh, things like this have collected this particularprotein, this little tiny compound from bacteria, and we can inject it into animals andsort of mimic a pathogen attack and stimulate their immune systems without actuallymaking them super, super sick. So I can use this lipopolysaccharide to make the birdsfeel a little sick for like a day kind of like a sort of flu symptoms. So, um, you know, theybecome less active. They're more isolated. They want to like snuggle up and stay tothemselves. They don't really eat very much just like people it's the same sort ofresponse that we have to feeling sick.Saintsing: Right. Okay. So I guess making them sick makes their gonadotrope and access say don'tmate or that's like theoretically what you're looking at here.Alonge: Exactly. Yeah. So, um, the funny thing about it is that there's been some work doneshowing that actually, if you make male birds feel sick, um, if they're alone, they'll actsick, they'll do all the things that I just described and sort of feel really bad forthemselves. But as soon as you introduce some sort of female bird into their area, theywill totally mask their sickness behaviors and take advantage of the meetingopportunity. SoSaintsing: That’s pretty funny, that's like a what the man flu thing. Yeah.Alonge: Yeah, totally. So, so I guess on the one hand you would expect that yeah. If you feelcrappy, you'e not going to be interested in reproducing, but at least for male birds,maybe unsurprisingly, they don't seem to really care. And they're like, hey, I have thisreally good opportunity here. I'm not going to let this pretty lady know that I'm notfeeling so good. And I'm going to try and jump on this chance while it's around. Saintsing: Yeah. But then the females it's different. They...Alonge: Yeah. So we don't know. That's a great question. So part of what I'm working on is thataspect of it. So when females are experiencing some sort of immune challenge, how dothey make decisions about their reproductive opportunities? Um, and the project I'mworking on now is actually looking at how they deal with managing their parental careduties while also feeling sick. So more of like, okay, they're already raising babies orinvested in reproduction, but now they're experiencing some sort of immune challengeand how, yeah. How do you choose what's more important in that moment. So that'swhat I'm working on now.Saintsing: Cool. And then you, you're doing something similar with bats, you're similar, like ideaseeing how pathogens might affect the reproductive response or the,Alonge: Yeah. So in a way, um, it's actually kind of a reverse question. So, uh, the, the projectthat I started in my second year of grad school was looking at, uh, fruit bats inMadagascar. And they were particularly interesting in terms of this question aboutreproduction and immunity, because fruit bats are known reservoirs for really gross andnasty zoonotic diseases. So things like Ebola, um, Hendra virus, rabies of course, is thefamous one. Um, so bats are pretty amazing because they can have all of these virusesand they don't exhibit any pathology. So they don't look sick, they don't get ill. Uh, theydon't die. Saintsing: That's really, I, I feel like probably this isn't in your wheel house and I'm just gonna playit. Do you have any idea? Like why, yeah. Why that,Alonge: Yeah, so it's not in my wheelhouse, uh, I'm not an immunologist, but there are definitelypeople who get really stoked about that immune systems, because it is so impressive.And if you could harness that power somehow, then you could protect a lot of people,especially in countries that are exposed to these diseases. Uh, so yeah, I don't knowwhy, but, um, one hypothesis is that they have really, really powerful innate immunesystems. So, uh, if you like, think back to anything you learned about the immunesystem, there's basically these two types of immune functions that we have. One iscalled this innate immune system. And one is the adaptive and the adaptive system is,you know, the one that contains things like antibodies and your B cells and your T cells.And it's a super specific response. Um, so it's not present all the time.Alonge: It will only appear in your body when there's something specific to be targeted. And theinnate side is more of this like generalist immune production. So, uh, there are lots ofcells that just sort of float around your body as like a general defense against somethingthat you might be exposed to. And this is typically things like bacteria or fungalinfections, um, and bats, some work has been done by people who are experts in thisfield and bats have these really, really heightened, innate, I mean, systems that actuallyprotect against viruses, which is somewhat rare. So they seem to have some sort ofadaptation within their innate system that, um, they can defend against any negativeeffects of these viruses, uh, and not get sick, but they do of course have live virus. So thebad thing is that they pass them on to everything that they come in contact with. So it'sactually like cool that they can do this, but really, really bad for everything else aroundthem. Yeah.Saintsing: Cool. So, sorry, I caused all right. I interrupted you, you were talking about how yourbat, uh, project is the inverse T.Alonge: Yeah. So bats can Harbor these gross diseases, which is cool and presumably a littleexpensive in terms of energy. So, uh, the, the optic sort of question I'm approachingwith the fruit bats is how, uh, sort of maintaining these heightened immune defenses toprotect against viral disease might affect their investment in reproduction, um, oralternatively, how, uh, their immune systems could be effected in terms of innate versusadaptive immunity across stages of battery production. So, like I said before, bats arereally, uh, fascinating because they fly they're mammals. So females who are pregnantare carrying around all this extra weight, um, and shuttling, lot of their food resources totheir developing baby. And then even after the baby bats are born, they carry themaround everywhere. So, uh, it's pretty rare that a baby bat would be left behind. Sothey're also, again, carrying all this weight for quite a long time. Um, the fruit bats Istudy, they hang out with their moms for about three months, um, which is yeah, a lotof extra weight and responsibility and yeah. Maintenance for these parents.Saintsing: And then after the three months, the babies are off on their ownAlonge: On yeah. Independent off to college.Saintsing: So it's not like a, it's not like a bird situation where you have, you know, the, the babybirds in the nest waiting for food. You don't have bats like hanging from the baby bats,hanging from the ceiling, waiting for parents to get back.Alonge: I mean, there are some species, typically smaller types of bats. Um, occasionally we'll dothis, but it's rare most, uh, female bats will carry their babies around for the entire timeuntil they're ready to be independent. Um, and males, don't really a lot of bird speciesdo exhibit like by parental care. So both the female and the male will raise the offspringor contribute in some way. And for bats, that's not the case at all. So the females willbasically take on all of the parental care duties and males don't really spend any timewith the female that they've chosen to pair up with or their baby. So, yeah, it's kind of aone and done.Saintsing: Yeah. That's so interesting like that they're flying around with babies on there, but likebats, they're like a lot of the cool things they do. Like it, it, they need to be reallymaneuverable right. And tight. So it's, yeah. It's interesting that, yeah,Alonge: I imagine, I mean, I don't study this, but I imagine that there's probably like increasedpredatory risk and things like that. Uh, in terms of being a parent bat at any moment intime, you're probably not as agile as you might be otherwise. Yeah. Yeah. Interesting.Saintsing: Yeah. This is just a reminder that you're listening to The Graduates and I'm speakingwith Matina Alonge. What kind of, what kind of things do you actually do in the lab? Likehow do you actually study the immune response at bats?Alonge: So it can be challenging. So some of the work that I do is in the field and some of it is inthe lab. So for a lot of the bat research that I do, it's largely all done through samplingstuff in the field. So collecting and catching animals in the wild, uh, I always do nonterminal sampling on those animals. Bats are really valuable part of the ecosystem. Andthere's like a number of things that threaten a lot of the populations across the world.So, um, I do my best to never, yeah. Need to do any research that requires euthanizingany animals, um, for that reason. So of course it's a tricky thing, right? If you'reinterested in hormones and especially things related to the brain or how the brain mightbe responding to some sort of challenge or regulating reproduction, you can't look at abrain in great detail in a live animal. So, um, yeah, so it's tricky finding that balance. Ithink of collecting meaningful data that can inform our decisions and inform ourunderstanding of the biology of these animals, but also making sure that we arerespecting them and protecting the populations that exist. Okay.Saintsing: Yeah. So you like in the field, you just kind of take a blood sample or something?Alonge: Well, a lot of the hormone measures are all done in blood, so that's makes things quiteeasy, I guess. And it';s amazing. I think once you start trying to figure out, you know,okay, I have this blood sample, what can I do with it? What information can I get fromit? You can get a lot from like a tiny little, you know, drop of blood. Uh, it's impressive.So I can measure hormones. I can measure various aspects of immune function. Yeah.It's a pretty powerful sample and very easy to take.Saintsing: Okay. So have you always been interested in, I guess, biology in general and morespecifically in eco physiology?Alonge: Wow. I had a feeling you were going to ask me that, but uh, I still feel unprepared toanswer that question, but so I don't,Saintsing: It'd be hard all of a sudden, you're just like going along and you're just like, this is whatI'm doing. And then someone asks you why. And you're like, I don't know why.Alonge: Yeah, so I guess I never, I don't have this like glamorous story of like, wow. I picked updirt when I was five and looked into it and it was like, wow, this is amazing. I want to bea biologist kind of thing,Saintsing: I love that your idea of that glamorous story is picking up dirt and looking at it. Butanyway, continue.Alonge: And yeah, and, and I don't come from a family who knows anything at least about, youknow, professional careers in science. Um, my parents aren't academics. Um, they'renot science people at all. Uh, so I think science is something I fell into because I wasgood at it. Like in high school, I did really well in my science classes. And then I sort of,you know, when you get to the time where you have to start considering college, I waslike, well, I'm good at this. I might as well keep doing it. Uh, so I did, but I think in termsof ending up where I'm at right now, that was more of a journey. Uh, I think I thoughtlike many people maybe, uh, and many students that I talked to you now that I interactwith in terms of teaching that medical school is like the career to go into, if you're goodat biology or interested in biology or something related to healthcare.Alonge: And so, for a long time in college, I just thought, okay, like, I'm going to go to school.Um, it also sort of fit with like maybe who I was at the time, because I was a prettycompetitive person. And, um, I liked to set really high goals for myself. And so I thinkpart of the reason I was interested in med school was only because it seemed hard todo. And so it was like this personal challenge, but then when it, when I was like a senior,I realized, Oh, I actually don't really care that much about pursuing this career. Um, so Istarted to spent, you know, four years in undergrad thinking I was gonna go to medschool, but then realizing I didn't really care. I didn't have a passion for that at all,relative to other people that clearly did. So yeah, it took some soul searching, I think, tofigure out how, what I loved about science and how to make what I love about science,what I do on a regular basis. Um, so yeah, so yeah, I mean, I've always been interested Iguess, in science, but finding how to make that work for my lifestyle was a little trickier.Saintsing: Right. So where'd you go to undergrad?Alonge: I went to Stony Brook University, um, which is on Long Island, New York all the way inthe East coast. Yeah. East coast. Yeah. Yeah. You're a fellow East coast. Yeah.Saintsing: So, you went to Stony Brook and you got through four years, uh, thinking you would begoing to med school and then it was just like, no, I'm not going to do that. Um, and then,so what did you do when you graduated?Alonge: So, I took a year off after graduation, mostly because this whole plan that I had formyself, I realized it wasn't going to happen. I'm, wasn't interested in trying to make thathappen. So I moved back home, you know, I waited tables. I sort of took time to figureout what other opportunities there are in science, outside of going to med school. Sothat was actually the first time I ever really considered research at all. So I never didresearch as an undergraduate. I never stepped in a lab. Um, yeah, I think, and that isprobably surprising for anyone who is interested in med school or knows anything aboutthe types of things and experiences you need in order to get to med school. Um, but Ithink I, like I said before, I just was never really driven to do it. So I never really soughtout research opportunities when I was an undergrad. Um,Saintsing: You were just like, the challenge was like getting all the, doing all the classes and likegetting all the A's and all the classes.Alonge: Yeah, yeah, yeah. Um, so I took a year off and then I ended up designing to get amaster's degree. Um, and part of that I think was also coupled with a pretty strongdesire to just move away from home and move out of New York state. Uh, I never livedsuper far away from home and I sort of felt like, you know, you have this feeling wherelike, nothing is here for me. Like I grew up here, I need like a change of scenery, newpeople, new place. So a master's program was good academically, but also it was achance for me to move somewhere, totally new, not know anybody and sort of startover. So I did that and I moved to Chicago and I did my master's at DePaul University. Itwas a super small program. There was like eight people in my, uh, cohort that startedwith me. And that was the first time I ever did research. And I totally like fell in love withit, like pretty hardcore. Um, and that was also my first exposure to physiology. So, uh,my project, there was a more of an eco-physiology project as well. So yeah, so that'ssort of probably what led me to my interests here.Saintsing: Cool. And then pretty much right after the masters, you want to, you knew that youwere going to do a PhD or?Alonge: So, I did. I remember this conversation that I had with my advisor, who was amazing atthe time as I was finishing. And I pretty much did know that I wanted to do a PhD, but Iwas really, really scared about making the commitment to do it because like, you know,it takes a long time. You also have to move somewhere new, most likely. And I wasreally comfortable in Chicago and I really liked my life there. Um, and I wasn't sure whatI really wanted to be in terms of a scientist. I felt like when you decide to get a PhD andpeople have varying opinions about this in mind maybe has changed too, but youstarted by deciding for yourself what you are going to become in science. Um, youknow, so I wanted to be sure I was selecting a field and selecting a topic that reallymattered to me and that I would be excited about in the long run, not just, you know,what I liked on that day, what's in style, what's on trend.Alonge: Um, and the other thing is I had a really great Masters mentor and advisor. And so Iwanted to make sure that I found someone who is going to be really great as a PhDadvisor too. So I took four years off before starting my program here. And sometimes Ilook back and think, wow, why didn't I do that? Like, I could have been almost done withmy PhD or done with my PhD by now, but I think that I grew a lot in that time andfigured out who I am as a person and what I like about science. So, um, yeah, sometimesI think, man, I'm like on the older side of people, uh, in my program, but on the otherhand, I think that I, yeah, I learned a lot during that time that I wouldn't have learned if Icame right into grad school.Saintsing: Yeah, for sure. I think, yeah. I mean, you kind of, yeah. The PhD is just like aboutlearning to be a scientist. So, you know,Alonge: When do you Learn about life when you're, you know,Saintsing: I guess my thought, like, you know, so you're doing that outside the program then, youknow, you're basically contributing to that education anyway. So it';s all part of theprocess, especially if you want to, ultimately you want to be an academic scientistultimately. So, you know, if you need it or like if there was something that helped yououtside of a PhD program right. Then that is useful to your ultimate career goals. Yeah.Um, so what did, in those four years you worked in a lab, like as a research technician orsomething like that?Alonge: Exactly. Like pretty the, you know, the standard common job that people might end itend up in if you have a bachelor's or a master's degree in science. Um, so yeah, I workedin some labs. I was a technician helped on other people's projects, lab manager, thatkind of thing. But, um, I think in that time too, it was just a reminder that the thing thatis so cool about science, um, when you're in research and doing your own work is thatyou sort of like create this little idea. That's like your baby, you know, and you like spentall this time crafting it and shaping it. And then you're trying to like support it and raiseit and like invest all this time in it and share it with other people. And, um, so whenyou're a technician or a lab manager, for me, the real bummer side of that was just likedoing other people's work and not being able to, uh, be excited about my own questionsand my own ideas.Saintsing: So, as you know, as a host, we typically end, uh, with a moment for the guests toaddress the audience on any issue. They'd like, uh, is there anything you'd like to leavethe audience with?Alonge: Yeah. So flying animals are so cool and there's really outside of, you know, insects andthings, but there's not that many flying animals. There's tons of bird, species and tons ofbaths, but those are like some of the only truly violent animals that we have broadly.And that's so cool. Yeah. Valance. Um, so yeah, I think that the next time you're hangingout and you see a bird fly or see about five, just like appreciate how cool that is.Saintsing: Alright, thank you so much for being on the show Mattina. And we look forward to thenext episode that you host.Alonge: Thanks for having me.Saintsing: Tune in in two weeks for the next episode of The Graduates.
12/17/2019

Chris Keckler

Andrew Saintsing: Hi, you're tuned into 90.7 FM KALX Berkeley. I'm Andrew Saintsing and this is The Graduates, the interview talk show where we speak to UC Berkeley graduate students about their work here on campus and around the world. Today, I'm joined by Chris Keckler from the Department of Nuclear Engineering. Welcome to the show, Chris.Chris Keckler: Thanks.Saintsing: It's great to have you here.Keckler: Yeah, I was excited that you reached out to me and asked me to come on the show.Saintsing: Yeah, I'm really interested to hear more about nuclear energy. I, I feel like my experience learning about nuclear energy is mostly, well, now Chernobyl has a few things, or The Simpsons.Keckler: Yeah, that's pretty typical of what I hear from people.Saintsing: Yeah, do you… and, I guess that's pretty problematic, right?Keckler: It's not great. It… you know, like anything people come in with their own biases, and it's just with nuclear, almost everybody comes in with a negative bias.Saintsing: Right.Keckler: So, you know I guess almost part of the reason that I was so excited to come here to talk to you today is because I like to try to dispel that wherever possible.Saintsing: I guess first off, like, should… nuclear energy is not that dangerous, right?Keckler: Well, so, so nuclear energy is, should be viewed – the way I like to think of it – should be viewed in the context of any other energy source, so in the same way that we get a lot of energy from coal or natural gas, those have drawbacks, right? And, the same thing goes for – people don't talk about them as much, but – the same thing goes for solar and wind and definitely hydro, especially big hydro has a lot of problems, and nuclear as well has its own potential issues, so really I always like to, kind of when I talk to people, I like to frame it from that perspective: nothing is perfect, you know? We don't have a silver bullet for the energy problem, which is why we still have like seven different energy sources contributing majorly in the United States.Saintsing: Right. Fair enough. So, why is nuclear energy better than other energy sources?Keckler: When you, when you kind of go and do a very apples-to-apples comparison of a lot of different important metrics, some thing's come out on top for some categories. Like, for instance, nuclear energy has the smallest footprint of land or total resource usage, and that's just purely because of the physics of how nuclear energy works. It's about a million times more energy dense than other types of fuels. Especially, I mean that's like solid fuels. When you start talking about wind and sun, it's significantly higher in terms of its energy density, so that allows it to be very compact and to use very little resources. So, that's one really good thing about nuclear. People – the population is obviously increasing, and the competition for resources from, from people, from industry, whatever is also increasing at an enormous pace, so when we start to look at things like environmental, a lot of environmental concerns can be boiled down to, we have a very large population, and therefore, we need to have, you know, 7 billion of every item in the world, and nuclear energy in my view is almost uniquely suited to be able to support that sort of population growth and population density because of the energy density that it has and the small footprint that it requires and also the unique – this is not something people typically think of, but – the unique safety characteristics of nuclear energy.Saintsing: You're saying it's safe?Keckler: I'm saying it's very safe.Saintsing: OK.Keckler: It's extremely safe. If you look at the historical record of all different forms of energy, nuclear actually comes out on top in terms of, you know, key metrics. Like, it's a very morbid thing to talk about, but like the number of deaths that can be attributed to energy generation from whatever source you're talking about, it's well known at this point that coal, you know, contributes to a lot of deaths around the world primarily through things like air pollution and then like the, the slag and ash that comes off of burning that. Other things, you know, like hydro, you might think of as being generally pretty safe but when there is a failure, like a dam failure, lots of people often die, so you know we have, at this point, many years of historical data of energy generation and the negative consequences of that and when you really stack them up and nuclear is actually about the best. Now it's ironic that you know the few accidents that there have been in nuclear, first of all, cause very little harm in terms of actual impacts on human populations, but they are – you know, you saw this Chernobyl TV show that we've mentioned earlier – they're just highly broadcasted, you know? Everybody knows about them. They know three words, right? If you, if you're an anti-nuclear person, you say Three Mile Island, Chernobyl, and Fukushima, all right? And, that's enough usually to stop the conversation, but if you take it one step deeper and actually understand what happened in those situations, the toll on human health and the environment is extremely small.Saintsing: Why do you think those disasters have such, like, a place in our collective psyches? Like, is that just because…Keckler: That's a really good question. I wish I knew the answer to that because then I think I could do more to try to fight it.Saintsing: Yeah.Keckler: But, yeah, a lot of it’s historical. At least that's what a lot of people chalk it up to, you know? We started the nuclear world with nuclear bombs, right? And, for a while that's all anybody liked associated with that, and then, kind of in the early stages of, of nuclear power there was Three Mile Island, which led to no deaths, no human suffering almost at all except for like the town of Harrisburg kind of freaked out for a bit, and I don't know. It's just, it's just left a permanent stain on, on nuclear, and there's a lot of people that are older, I think, that are more passionate about that than are a lot of younger people right now. That seems to be, at least in my view, the trend.Saintsing: Right, so it's kind of just like maybe that it's wrapped up in ideas of war and that we've seen like, when it is used for the purposes of war, it can be very effective in that?Keckler: Sure, yeah, but then a lot of people who are younger, more my age and even younger than that, you know, they're looking at the world that we face coming up: of climate change, you know, energy scarcity, poverty around the world, and they're kind of reassessing the situation a little bit, I think, with more of a level head.Saintsing: Right.Keckler: At least that's, that's my viewpoint.Saintsing: Yeah, for sure.Keckler: And, trying to you know reevaluate: is nuclear something that we should be keeping on the table or even expanding? And, you know someone like myself came to the conclusion that: yes. Yeah, that is the case. Some people don't. That's fine, but I think that's, I think climate change is probably the primary reason why a lot of people are really weighing that question recently.Saintsing: Right, and it's gonna be way more effective like you were saying than wind and solar which would obviously be clean energy sources?Keckler: Sure, yeah, well, wind and solar I have, I have no problem. I think a lot of people that get labeled as pro-nuclear get labeled anti-wind and solar. I think that's a thing that should be avoided because there's no real inherent, at least the way I look at it, there's no real problems with wind and solar. It's just that the – I don't think that they can do it alone, and so, I'm all for expanding clean energy and I think the clean energy includes nuclear. I think, I think it by definition includes nuclear, so, but wind and solar are in there, too. So, if you want to put a solar panel on your house, do it. You know? It messes with the grid a lot, but it's uh ultimately will be good, I think.Saintsing: Okay, so I guess, what, what are people doing in terms of research in nuclear energy? I mean, is it… are people trying to make nuclear energy more efficient and safer? Where are you? What are you trying to do?Keckler: So, in, in the nuclear energy world, I think there's kind of two rather large camps right now in the United States. I don't know if you know this: the amount of electricity that's generated from nuclear is about 20% of our total electricity.Saintsing: I did not know that. That’s like a decent portion, I guess. More than I thought, yeah.Keckler: Yeah, it's, it's more than almost anybody realizes because these nuclear plants are typically not things you see very often, so you don't realize that there's a hundred of them in the country right now producing a lot of energy.Saintsing: They're just like far away from…Keckler: Yeah, usually they're, I mean, they're not in downtown, right? And, they're usually kind of more in like the farms on the outskirts of big cities, and they're not typically like right next to the highway, so you don't see them.Saintsing: Right.Keckler: You know, when I'm driving on the highway, I know where they are, and I'm looking for them because I'm just a loser, and I, I'm like, you know, craning my neck out the window trying to see these things, but if you're not looking for it, you won't see it.Saintsing; Yeah.Keckler: So, they're out there, like silently generating about 20% of our electricity in the United States. There are a lot of people that are focused on trying to keep those 100 nuclear plants operating for as long as we possibly can because they're a, they're an investment which has already been made and they're doing a very good job as is. Eventually they'll need to be shut down just because they get old, you know? The average age of a nuclear plant in the United States right now is something like 50 years.Saintsing: It… they just, like because the way nuclear energy…Keckler: No, it's not that, but almost no industrial facilities in the world operate for any longer than, you know, 80 years.Saintsing: Right.Keckler: When you think about when the Industrial Revolution really began in the United States it was like 1900, you know? Late 1800s. So nothing is that old. Things, even just mundane things, will degrade over time, you know? The integrity of your building…Saintsing: Right.Keckler: It's not, it's not, it has nothing to do with nuclear power. It's just a building you happen to put it in.Saintsing: But, you could – they, they could repair the existing…Keckler: They do a lot of that. So, that's, that's kind of the primary area of work and research in the older side of nuclear is how can we maintain our existing investments to maximize the productivity that we can get out of these things. So, that's a huge area of research and work. A lot of it in industry, and they've done a really good job with that. The other area which is more where I work is advanced nuclear. So, it's like how can we design the new set of nuclear power plants to be better than the old set because we know that there are drawbacks to the things that we've built before, we know we can improve it in a number of ways. So, how can we realize those improvements which we know are possible and do it affordably? So, that's really kind of like where new nuclear, what a lot of people would say advanced nuclear, is going.Saintsing: I guess, what are the big trends or like what specifically are you looking at?Keckler: So, a lot of these things are actually not new ideas. They're just things which we've struggled with for a long time or there's never been really the right opportunity to implement them. A classic example of which is what's called breeding. So, nuclear fuel breedingSaintsing: Interesting.Keckler: All right, so basically in, in uranium when you go out and you mine some uranium out of the ground – which is what we're using in a nuclear reactor.Saintsing: Right.Keckler: Only a very small part of that uranium is actually useful in the current reactors that we have right now because there's two what are called isotopes.Saintsing: Right, so what are isotopes?Keckler: For a particular element, two different atoms of the same element can have a different number of neutrons.Saintsing: Right.Keckler: And, depending on that number of neutrons that they have, it is either useful in a nuclear reactor or it's not, so a lot of the uranium is not just because of how it happens to be, so, but, but the thing is about that the stuff, that is – you know I'm, I'm doing air quotes right now – the stuff that is “not useful” we can actually turn it into very useful stuff for burning inside of a nuclear reactor, so for producing lots more energy, and the way we do that is we allow some of the uranium 238 isotopes (so it has 238 protons plus neutrons), we allow that to absorb one more neutron, and…Saintsing: You allow it to absorb one more? It's just like: it didn't know it could do it before and now it can?Keckler: That's a good question. So, you know in the, in, in the room we're sitting in right now, there's not like a bunch of neutrons flying around. There's, there is some very small amount, okay?Saintsing: I didn't even know… I thought it was like neutrons are in atoms. I didn't even know they were flying around.Keckler: Yeah, yeah, so they're, um, we get all sorts of radiation produced from particles in space coming into Earth and interacting with the atmosphere, so this is producing like a cascade of radiation that is constantly interacting with everything – yourself and everything around you. But in a nuclear reactor we have lots of neutrons moving around okay because that's how we're unlocking the energy from the fuel by interacting the isotopes with neutrons, so if we take the uranium 238, the “not useful” isotope, and put it inside of a reactor, even though it's not going to produce energy for us, we can (I said allow before), we can force it to absorb a neutron.Saintsing: Right.Keckler: And, that will turn it into an isotope of plutonium which is another element which is actually also extremely useful inside of nuclear reactors for producing energy.Saintsing: Wait, you, you turned it into plutonium?Keckler: So, what happens is that uranium 238 gets a neutron. For like a fraction of a second, it will be uranium 239. That then undergoes what’s called a radioactive decay.Saintsing: Okay.Keckler: So, one of those neutrons then is going to turn into a proton and a neutrino, and because it now has an extra proton, the element has changed because the proton is what determines the element.Saintsing: Right.Keckler: So, there's actually a middle step, but if you undergo two of those radioactive decays, you'll end up with plutonium 239.Saintsing: Okay.Keckler: Which is, I mean, it's, it's very good at unleashing energy which is why most nuclear weapons are made out of plutonium 239, but it's also an extremely good fuel for producing electricity.Saintsing: This is, this is what makes up the green glowing rod on the Simpsons and stuff?Keckler: I'm sure the Simpsons have no idea what's in there, but that is what they depict as a green glowing rod.Saintsing: Does it… it doesn't glow, would you say? Or, it does?Keckler: Nuclear, if you look, if you could look inside of a nuclear reactor as its operating (there are some like research reactors where you can do this, you can just look through the water from on top of it) it glows blue.Saintsing: Interesting. Okay.Keckler: When it’s, when it’s operating. So, it's not actually the fuel, but it's kind of like a, just a halo kind of look around it where the water looks blue.Saintsing: Cool, it's a nice-lookin?Keckler: It's quite pretty.Saintsing: Pretty, yeah.Keckler: So, that, that's one area of like advanced nuclear is, you know, to wrap that all up, it's called breeding.Saintsing: Right.Keckler: So, we take things that were not useful as fuel before and we turn them into useful fuelSaintsing: And so, you're just trying to make that process more efficient?Keckler: Yeah, and it's, it's kind of difficult to enable that for a lot of kind of convoluted reasons, but it's something that we know is possible, that's been demonstrated as possible in full-sized nuclear reactors that have operated, so we know we can do it. It's at this point a matter of like refining this principle working it into something that will be attractive to like utility companies that want to purchase it, so…Saintsing: Right.Keckler: So, it's, it's, it's an idea that's been around for a very long time, okay, but one that has kind of so far eluded commercial implementation. Okay, so another, another area of advanced nuclear is just improving things like the safety characteristics of nuclear reactors to make them cheaper and again more attractive to utilities, and I do, when I say improve the safety characteristics, I don't want to imply that that means current reactors have bad safety characteristics. They have good safety characteristics, but they require special attention actions by people that work, they're called operators you know, to do things, and there's a lot of very complicated machinery and equipment that goes into these things and if we could make it simpler so we don't need all these extra systems to make the reactor as safe as it is now that would be desirable because it would make it cheaper and it would make it smaller. All these things. So, these are… that's, that's one big area.Saintsing: You’re listening to The Graduates. I'm speaking with Chris Keckler from the Department of Nuclear Engineering. So, your research falls more into making, improving the safety characteristics of nuclear reactors, right?Keckler: Yeah, I do. I kind of do work in both of those fields that I mentioned before, but so kind of the idea is that the way that we control a nuclear reactor typically is through what's called control rods and basically what these do is they are pieces of material that we move inside and out of the reactor which absorbs neutrons preferentially to the fuel absorbing them, so what that means is then we have less neutrons to go on and produce energy, so by putting in the control rods we, what people call, we poison the reactor, so we shut it down basically because there's no more neutrons anymore.Saintsing: Okay.Keckler: So, that's, that's, you know what's been done forever.Saintsing: Right.Keckler: And, that requires somebody or some sort of computer system to identify that there's a problem and then push a button whether it be real or a virtual button if a computer is doing this to flip the control rods into the reactor, and it requires, you know, a motor to push the, you know, to spin a bunch of gears and the control rods go inside the reactor. The idea behind one of the projects that I work on is that we can maybe do, have this same type of process occur but without having anybody do anything or a computer do anything, just relying on physical principles in order to make that happen. The idea is that you could, you know, control rods are typically solid, in, in solid state, but the properties for absorbing neutrons, it makes no difference if it's in solid state, if it's in liquid state, if it's in gaseous. It just depends on the material itself, so an idea is that you could have like a liquid reservoir of some sort of like control rod material but it's in liquid form this time below the reactor, and when the reactor, say the reactor starts to, you know, get out of control going to a higher power, we don't like that then that's going to cause the reactor to heat up because it's producing more power than it was before. So, it's going to cause the temperature of the reactor to go higher than we want and when anything increases in temperature, most things when they increase in temperature, they actually thermally expand.Saintsing: Right.Keckler: So, kind of the idea here is that if we can allow this poison control rod material to thermally expand in the right sequence when the reactor starts to go out of control, it will thermally expand in such a way that it will be pushed into the core. It will like push itself into the reactor core and then absorb the neutrons that we want it to.Saintsing: Okay.Keckler: So, instead of somebody like pushing a button that triggers a motor that causes the control rods to go in we just run want to rely on purely passive aspects of physics, you know. This is actually very elementary physics that I'm talking about here.Saintsing: Right, so you have to identify material, so you have to like make materials that can perform this function?Keckler: Most of the trick in this type of work is putting the materials into a proper configuration that will allow this process to you know unfold in the way that I described. The materials to do this are already clearly identified. There's not that many materials that are really good at absorbing neutrons, so we're pretty limited from that perspective, especially when you pair that with: we need it to be liquid at the right at the temperatures that our reactor is at.Saintsing: RightKeckler: So, you know that's kind of not that many choices from there, but we need to be able to incorporate that into the reactor. Like, for instance, we don't want this liquid to just go into our, into our reactor uncontained because then it will contaminate everything and if we want to start the reactor back up we still have a bunch of control rod material inside the reactor.Saintsing: Right.Keckler: So, we need it to be able to go in but also to come back out cleanly.Saintsing: Right.Keckler: And, we need it to do it at the right time in the right sequence with the proper amounts. It's quite a complicated like engineering problem.Saintsing: YeahKeckler: From a physical perspective, it's actually pretty simple and extremely elegant.Saintsing: Okay, so physics, yeah, you got it. Yeah, it's the engineering you're spending like all your time on, and like what do you, are you modeling it? Or, like how are you actually trying to solve this problem?Keckler: So, all of my work is computer modeling.Saintsing: Okay.Keckler: That's a pretty normal sequence of steps in like the nuclear engineering world is if you have a new idea first thing to do is model it because at this point we're pretty good at simulating a lot of different physical phenomena and doing it relatively accurately at least to the point where we can say this is either a good idea or it's not. Once you have you know the green light that this is a good idea based off of all the simulations then if somebody is interested enough they'll pay for the experiments to be done to actually verify that what you think is going to happen is what's going to happen, and because in nuclear a lot of things are very expensive, the experiments typically don't get done until after a lot of computer modeling has been done.Saintsing: I gotcha. So, outside the scope of your PhD?Keckler: Yeah, yeah, yeah, it's definitely, it's definitely not in my PhD, but we actually we think we've gotten to a point where the, the simulations tell us that this is a good idea.Saintsing: Oh cool.Keckler: And, that it should be pursued, you know, if the interest is there.Saintsing: What's the career kind of look like for nuclear engineer?Keckler: It's, right now there's kind of a big sea change going on in the nuclear energy world and that is, I think, motivated mostly because what we talked about earlier. There's a lot of younger people that are very interested in solutions to climate change. Solutions? Something that can mitigate climate change.Saintsing: Right.Keckler: So, there have been actually a lot of startup companies related to nuclear power, nuclear energy has historically been dominated by a couple companies (General Electric and Westinghouse). Those are huge companies, and they've done the same thing for very long time, so there are, you know, handful of companies that are interested in changing that and doing something new. So, a lot of people are going into this kind of like startup industry that's forming right now. There's still a lot of people going to, into national labs because you, it's kind of a weird middle ground between academia and industry in the national labs at least in the nuclear energy part of the national labs.Saintsing: All right.Keckler: So, a lot of people that get PhDs might not want to be a professor, but they still probably like doing research or else they wouldn't have gone to grad school in the first place.Saintsing: All right.Keckler: So, the National Labs can kind of like offer them a halfway point.Saintsing: I see. Yeah, why did you want to get into nuclear energy? Did you always know that you were gonna be a nuclear engineer, engineer?Keckler: No, but I definitely always knew I would be an engineer.Saintsing: Okay.Keckler: When I first started out my undergrad, I was a chemical engineer for one year, and chemical engineering is so outrageously broad, so you can do almost anything with a chemical engineering degree, but that wasn't exactly shown to me based off of just the people that I happened to interact with. It was kind of like: there's the oil industry, or there's, you know, like, I don't know, just things that I think are trivial. Like, like coatings on cars or something.Saintsing: I mean that's pretty useful.Keckler: It's important. It's useful, but it's not gonna change the world.Saintsing: Oh, yeah.Keckler: I was very interested in energy for a long time, and I kind of did this – what I was talking about in the beginning of this interview – like assessing different energy sources on an even basis and trying to think what might be the best way for me to go, and nuclear energy was just something that appealed to me from, from that process, and, you know, I should say right here that chemical engineers can totally be involved in nuclear engineering. It would… We have, we have skillsets that overlap to such a large degree.Saintsing: You got to pull back all that shade you threw at chemical engineering.Keckler: My dad's a chemical engineer, you know? I have no problem with it, but uh, it's just kind of, I just didn't get the greatest impression when I started out.Saintsing: Right, so is that kind of maybe why you wanted to go into engineering? Your dad was a chemical engineer and that's…Keckler: I think my dad, definitely. It's not be… you know, I didn't look at him, and I said he's a chemical engineer, I should be an engineer, but the things that he was interested in and therefore like involved me in as a kid were so engineering. I mean like looking back on it, it's like I definitely was going to be an engineer just based off of the things that I did when I was younger.Saintsing: Like what kind of things?Keckler: You know, anytime something needed to be fixed in my house, it was, it was the stupid process of let's just like break it even more first because we like need to really thoroughly understand what's wrong with this thing, and then we'll fix it, and we'll fix it ourselves, so…Saintsing: Right.Keckler: We're not calling the… I don't even think I ever saw a repairman in my house as a kid. Like any item, the cars at my house were constantly being taken apart and like just destroyed before ultimately being fixed.Saintsing: Did they always get fixed?[Laughter]Keckler: The answer to that question depends on if my dad is listening to the radio show or not.Saintsing: I guess, I guess that’s your call.Keckler: Definitely we had a lot of very old stuff because we could like always somehow scrap it back together.Saintsing: Right.Keckler: So, we had a lot of things that were just hanging on by a thread for like ever, you know?Saintsing: Okay.Keckler: It was interesting, but it definitely made me curious about how, how things work, and not just how things work, but how practical things work. I think it's one thing to be interested in pure physics, to just want to know about, for instance, space because you know some beautiful mysterious reasons, but that's never been the case for me. Like I've kind of… as I've gotten older, I've kind of looked back on my childhood and been like, “Why wasn't I interested in dinosaurs?” You know? Like dinosaurs are really cool, but as a kid I just didn't care. I was more interested in like taking apart my, my Bop It. You know? Like just for fun.Saintsing: Right.Keckler: So, I don't know. It was, it was clear that I wanted to know how things worked but only things that like were of use to me.Saintsing: Right.Keckler: Not just like these esoteric concepts.Saintsing: Okay.Keckler: So, I think it was very clear that I was gonna be an engineer.Saintsing: Yeah.Keckler: Also I had about 10 billion Legos.Saintsing: Is that, like every engineer had Legos as a child?Keckler: I don’t, I don't know if it's that way, but it's definitely the other way. If you had that many Legos, he's definitely an engineer at this point.Saintsing: I got you. Okay, so you went to college thinking you'd be a chemical engineer and then you decided that nuclear engineering was just like way more useful.Keckler: Oh yeah, I just thought it was more directly applicable to what my ultimate goals were, which were to do something useful in, in the climate-environmental-energy intersection.Saintsing: You – what school did you go to?Keckler: So, I actually started at the University of Cincinnati for one year. That was, I was actually the fourth generation of engineer to go to that school. My dad and then his dad and then his grandpa, but I transferred after one year because Cincinnati didn't have a nuclear program.Saintsing: Okay.Keckler: So, then I went to the University of Illinois for the rest of my undergrad.Saintsing: So, then you graduated with your nuclear degree in nuclear engineering, and then, did you go straight to the PhD?Keckler: Yeah, I came directly here. I'm originally from Chicago, so Illinois was close to where I grew up, I could have gone there for grad school. I'm sure I would have had a great time. I just was like, I should go somewhere else.Saintsing: Yeah.Keckler: Just to… I think it's always good to have a different perspective on a lot of stuff, so me and my girlfriend at the time, we both went to Illinois, and we both came here for grad school and now we're married.Saintsing: Nice. You met through…Keckler: We met in undergrad in, in nuclear engineering.Saintsing: Nice, nuclear engineering brings people together.Keckler: Honestly, maybe.Saintsing: Well, this has been a lot of fun, but we're running out of time on the interview, so typically at the end of the interview we just offer a chance for the guests to address the audience.Keckler: Because I came here or, or because my reason for agreeing to do this was because I like to spread the word about the benefits of nuclear…Saintsing: Right.Keckler: I'll end on that.Saintsing: Go for it.Keckler: Bring it full circle.Saintsing: Yeah.Keckler: You know, pretty much the one, the one message I'd like to get out is just for people to have an open mind about nuclear power because it really is in my view the biases that people have coming in that are preventing more people from being interested. If you go into something thinking inherently that you're not interested, you're not even going to listen when somebody talks, but if you have an open mind about energy in general, I think there's a lot to be learned, and it's not as easy of a question as people might think it is. People think, just build wind and solar, we're done.Saintsing: Right.Keckler: I think the answer is going to be a lot more complicated than that. Therefore, go nuclear.Saintsing: Keep an open mind. Go nuclear. All right. Thank you so much for being on the show.Keckler: SureSaintsing: Today I've been speaking with Chris Keckler from the Department of Nuclear Engineering. We've talked a lot about the value of nuclear power. Tune in two weeks for the next episode of The Graduates.