Fellows Feature: Jaehee Kim

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Jaehee Kim is a postdoctoral scholar in the Department of Biology at Stanford University. She received her B.A. in Physics and Mathematics from Columbia University and her Ph.D. in Physics from Stanford University. Her research interests include mathematical properties of admixed population phylogenetic trees inferred by neighbor-joining, the relationship between individual identifiability and ancestry information in CODIS forensic markers and non-CODIS microsatellite loci, and change of admixture fraction in a hybrid population mating assortatively based on phenotype over time. 

Can you tell us a bit about yourself, personally and professionally? 

I was born and grew up in Incheon, South Korea’s third largest city, where I was likely the most physics-y kid on the block. True to form, I received a B.A. in Physics and Mathematics from Columbia University and a Ph.D. in Physics from Stanford University. My graduate research focused on the study of quantum chemical dynamics in complex molecules. I developed an ab initio theoretical framework to numerically simulate light-induced excited state topology and nonadiabatic dynamics, as well as multidimensional statistical techniques to analyze molecular fragmentation patterns. Now, I am a postdoctoral scholar in Noah Rosenberg’s lab.

How did you end up here? What got you interested in genetics and science?

Like most physics-y kids, I always loved math and spent countless hours voraciously reading science magazines and Feynman lectures. I was amazed by how physical phenomena, from mundane everyday events to the creation of the universe, could be explained by beautiful mathematical equations. I believed that everything could ultimately be explained by the laws of physics. During graduate training in atomic molecular optical (AMO) physics, working with people from diverse fields expanded my research interests. After going to a handful of outer department talks, I was drawn to evolutionary biology—like many people, I always have the same age-old questions lingering in the back in my mind: “why are we here; where are we going?” (Charles H. Townes, 1997). The current lab is the perfect fit for me as it applies rigorous mathematical theory and statistical methods to the study of human evolution and population genetics. I still have a lot to learn, but I have been enjoying working in the lab very much so far!

Can you tell us about your current research and what you want to achieve with it? 

My current research deals with the development and application of a mechanistic model for assessing the effect of different admixture histories involving dynamic contributions of mutually isolated source populations on the ancestry of admixed human populations. Human mating is non-random to some degree, since most people marry individuals of roughly similar phenotype and cultural factors. The assortative mating alters genetic variance for the assorting trait and makes the traits more susceptible to selection over time, thereby changing the genetic structure of a population.

Since the ancestry information is propagated through genotype but mating is based on phenotype, mapping genotype to phenotype is a crucial step. Among many interesting results the model produces, correlation between ancestry proportion and phenotype is of particular interest as it gives us insight about the degree to which genetic differences give rise to phenotypic differences between human groups. This also helps us to answer important questions regarding racial classification beyond conventional phenotypic group-level differences that are believed to be a representative of a race or ethnicity, for example, skin and eye color.

Once gaining intuition from the idealized model, to simulate more realistic human population, the model can be further extended by including confounding factors such as dominance, varying heritability, effect size distribution across loci contributing to the quantitative trait, and linkage disequilibrium, as well as environmental perturbations.

Were there people in particular to whom you would attribute your professional success? What is it like working with your current lab advisor and his lab? 

My Ph.D. advisor, Prof. Phil Bucksbaum, has provided me every bit of guidance for becoming a better scientist and encouraged me to collaborate with people outside the physics department to branch out into new research areas. His genuine enthusiasm for science and encouragement kept me motivated when research progress was bumpy. From my graduate lab, Doug taught me the importance of scientific intuition over sets of equations and he has made working in the lab so much more fun and interesting. James showed me reasonable science could be extracted from suboptimal experimental data if you used good statistical methods.

My current advisor, Prof. Noah Rosenberg, believes in the interdisciplinary nature of the work and gave me a chance to work in his lab. He helped me transition smoothly into the new field by providing every possible resource, and guided me through the systematic and mathematical approach for understanding evolutionary biology. I have also enjoyed the camaraderie and benefited from the varied expertise of the group members.

What are your future plans? Where do you see yourself professionally in the next 5 or 10 years?

Long term, I see myself still working in the field of theoretical population genetics. Having my own lab and staying in academia will be the best-case scenario, but I would be happy with government labs or industry as long as I can do meaningful research with some freedom and independence.

What advice would you offer to other grad students or postdocs who are considering pursuing a similar educational and career path as you? 

  • Most physicists are proficient in math and programming, but still, the more the better.
  • Stay open-minded, look outside your department, and explore your options. There are tons of other interesting work going on that could use a physicist!
  • Have patience, and don’t rush. Research takes time, and some projects might not end up working out. Persistence is important, but at the same time, know when to stop and move on, and when to pause for now and come back later.
  • Have a life outside the lab, and cut yourself some slack. You’ll need it for your sanity.

Can you speak a bit to the role you see CEHG playing on Stanford campus?

I love the cross-disciplinary environment CEHG has created. It brings scholars from various fields, which encourages me to communicate with researchers outside my specific research area and broadens my knowledge. I believe the collaborative approach across different fields can produce creative solutions to challenging problems through a diverse array of tools.

For instance, during my graduate studies in physics, I have used techniques borrowed from biology—for example, genetic algorithm and spawning of wavepacket—in modeling complex molecular dynamics. I am excited to apply physics techniques to tackling fundamental problems in evolutionary biology and share my interests with others.

Tell us what you do when you aren’t working on research. Do you have hobbies? Special talents? Other passions besides science? 

I spend most of my free time training in the gym. I have played various sports growing up, but my current focus is in Olympic weightlifting. I also like trying out new fitness classes/workshops/gyms and enjoy reading sports science and physiology research articles.

Tweeting #CEHG17

The Fifth Annual CEHG Symposium was held in Stanford University’s Frances C. Arrillaga’s Alumni Center on March 6, 2017. It was an amazing day, with fascinating presentations on computational, evolutionary and human genomics and plenty of opportunities to visit with old and new friends over coffee and tea! And with 10 brilliant speakers, including keynote Carl Zimmer, and more than 160 registered attendees, CEHG17 was a definite success!

Did you miss the event or are you just curious what everyone was talking about? Click on the feed link below to catch up!

Read the curated twitter feed

Want to read more materials about our symposium? Check out our CEHG17 photo album on Flickr. An event report will be published shortly on our blog home page.

Want to learn more about CEHG?  Visit our website or follow us on Facebook and @StanfordCEHG.

Feature Interview: María Ávila-Arcos

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All images courtesy of Maria Avila-Arcos

María Ávila-Arcos is an Assistant Professor at the International Laboratory for Human Genome Research at the Universidad Nacional Autónoma de México/ National Autonomous University of Mexico). She was a postdoctoral researcher in the Bustamante Lab at Stanford University from February 2014 to September 2015, where she studied population genomics and global health. Before that, she studied in Denmark as a PhD student and then as a postdoc at the University of Copenhagen. She received her PhD in Paleogenomics in 2013.

This content is transcribed from an interview that took place on Stanford University campus with CEHG Director of Programs, Cody Montana Sam, and Communications and Outreach Manager, Katie M. Kanagawa. 

AfroMexico Project Description: In January 2015, a fieldwork team led by Ávila-Arcos, a CEHG postdoctoral fellow at the time, collected eighty samples from individuals living in Afro-Mexican villages in the Pacific coastal State of Oaxaca. In a pilot effort, saliva samples were collected, along with genealogical information, anthropometric and skin pigmentation measurements. Given the initial sampling success and the scaling feasibility, this effort has been expanded to analyze the genetic structure of Afro-Mexicans across the Atlantic-Pacific corridor. Mexico’s African roots have importantly impacted the current shape of the population, but they have yet to be represented in modern genomic surveys of genetic variation. The knowledge generated in this study will help characterize this important, yet neglected, third ancestry of Mexicans and will shed light on the genetic dynamics and implications of the slave trade in the Americas.

Why don’t you tell us a little bit about yourself, in the broadest sense? 

I grew up in Mexico City and I went to college in Cuernavaca, a town about 1.5 hours away. Since very young, when I was 18, I jumped straight into genomics and research. The National Autonomous University of Mexico’s (UNAM’s) campus in Cuernavaca hosts the Biotechnology and Genomic Sciences Institutes, and I was part of a very specialized, unique undergraduate program in genomics. It was kind of a pilot project with a reduced number of students and very good, research-driven work. It was apparently successful because most of us who graduated from that program found PhD or Masters degree positions abroad.

Can you talk about the intersection of medicine and genetics in your research? 

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I’m just starting now to get into that. Right now, I’m very interested in understanding the genetic structure of populations that haven’t been very well characterized from a genetics perspective, admixed populations in Mexico for example. First, you need to understand their genetics, how admixture is structuring them, and then you start to do more clinical studies on them, using this background. So it’s very basic research and then you build on it.

Since you got started in genetics, do you think the field has changed much? How so?

It was a dramatic change. Towards the end of my undergraduate program, I had to write a thesis and, in the last classes I took, I started to hear we had new sequencing machines and pyrosequencing, and there was this idea like things were happening. But then I started my PhD and the next-generation sequencing machines started this massive revolution in genomics and genetics research. So I knew nothing about how to handle this kind of data when I was an undergrad, because it was brand new. I had to learn that as a PhD student, and I had to teach myself these new programs, these new ways of handling massive amounts of data. That was a big change.

One thing we have seen, at least from your awesome lab meeting presentations, is how much you like doing fieldwork, and also making sure that community members are involved in the fieldwork and understand the research. So can you speak a little bit about that? 

Sure. Well I grew up with my dad being an epidemiologist; he did a lot of fieldwork and he would take me when I was a kid into the field. And his research focuses on children. In Mexico, we have a lot of malnutrition and basically his fieldwork involved weighing kids and giving advice to the families on how to better feed their kids. So I was part of that. I grew up doing this fieldwork with my dad, and then I went to school and I never thought I would go back to fieldwork again, but that image of him and also how involved he was with the community and how much respect he had for the community, is something that stayed with me.

And also something very important: when I came here to Stanford and I went to do fieldwork in South America with Karla Sandoval Mendoza [former Bustamante Lab member]. Her background is Anthropology and she also has a lot of experience doing fieldwork in the frame of genetics, so seeing her was really cool and seeing that we share a lot of the same philosophy on how to approach communities and talk to them. That was also something I learned from her.

So tell us about the communities where your fieldwork was located? 

South America was the most exciting. It was my first time doing fieldwork, collecting samples for genetic studies. So I went to Easter Island with Andres Moreno Estrada [Bustamante Lab alumnus] and it was really cool, because it was the second time he was visiting and he was giving results back to the community, so the effect it had on people, to get their ancestry results back, and also collecting new samples for new studies was very exciting. And I went to one community with Karla in Peru; it’s called Magdalena da Cao and we also collected samples there. More recently, I’ve been doing more fieldwork in Mexico with the AfroMexico project.

Does a particular person you’ve met while doing fieldwork, one of the community members, come to mind? And why? 

Yeah, definitely in Oaxaca, Mexico, there is Lucia Mariche, in the context of the AfroMexico project. She lives in Chacahua, an AfroMexican community, and she’s a community leader. Just being able to be in contact with her: she’s really proactive and you can see her leadership when you see her. And she’s also very nice and she was very collaborative. Basically, she was the one who opened the doors for us, to the other communities we visited. So people everywhere we went were like, “Lucy, how are you doing? How is your mom? How is your family?” She was great. She is my favorite person.

If you were to give advice to other people who are interested in doing fieldwork, who maybe don’t know how to get started with these communities, what would you say

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The first advice is you have to build or join a network that is already in place in these communities. You have to find your way through this network first to find a person who is in contact with another person, who is also in contact with another person, etc. So you just need to find that key person and then you’re part of that network, so that people in the communities will know you as part of that network and they will be more open to participating in your study.

Can you tell us a bit more about the AfroMexico project? 

Yeah, sure, that’s my favorite topic (laughs). My interest is characterizing the genetic makeup of AfroMexicans and the reason I am very interested in this is a nice story: while I was doing my PhD and I was more specialized in paleogenomics (ancient DNA), we got these samples from the Caribbean that were from the 16th century. We knew the people were born in Africa, but their remains were found in the Caribbean. Basically, the questions we had with these three ancient samples was: where were these people born? Where are they from? Because we knew, by the historical context, that they were probably brought to the Caribbean by the Transatlantic Slave Trade, and we wanted to know exactly where in Africa they were from.

In the study of the Transatlantic Slave Trade, the question of origins is a very important one and a central one. Because during the Trade, the place of origin–the geographic or ethnic origin–was erased from the records, or not even erased, but not even written or put in the record. Many people don’t have the tools to trace their actual ancestry because the record didn’t include them. So I had that question in mind, and that got me to think a lot about the slave trade in the Americas, and I started to read about the slave trade in Mexico, and the more I read, the more surprised I became, because it’s something you don’t hear much about in Mexico.

But just looking at the history, I realized that there was a lot of trade into Mexico from Africa. As I read more, I found that there are some places in Mexico where you see a higher concentration of people of African descent. So I wanted to see them and work with them because I had the same question: where did these people, their ancestors, come from and when were they brought from Africa to Mexico? That’s how I got interested. I called Carlos [Bustamante] and asked, “Carlos, can I go to collect samples?” And we had the IRB in place. The first time I went was this January. Many months in advance, I started emailing people and getting necessary contacts, so that by the time I got there, people were already waiting for me.

When you go to these communities, how do they themselves identify? 

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It’s becoming more political right now, because these people are fighting for recognition as people of African descent and a vulnerable minority as well. In Mexico, if you speak an indigenous language, then you have access to certain benefits, like scholarships or programs that support communities. But if you can’t identify as Afro-Mexican, because there is no box to check, you are also vulnerable. So if you ask people who are part of this initiative, they would say “yes, I am Afro-Mexican,” but if you ask people who are not, they would say “no, I’m Mexican, that’s just the color of my skin.” But for many people, there is a disconnect between the way they look and the slave trade many centuries ago. They don’t recognize themselves as being from Africa; they see no connection.

In the last fieldwork I did, I asked the question, “how do you self-identify?” In Oaxaca, for example, people are more politicized because there are more movements there for recognition, but in Veracruz, almost no one recognizes themselves as Moreno, or Negra, or Afro-Mexican. Very few people, so it’s interesting.

That’s interesting because there are also those types of discussion within the American black community, as to how you identify and how much you identify with the African continent. If you were to compare and contrast slave routes and the slave trade in America vs. Central America and Mexico, how would you describe it?

It’s very different, and I think that’s one of the important reasons why we need to study Afro-Mexicans, because it just has a different history. We were a Spanish colony and, as a Spanish colony, the deals they were putting in place were different than the British colonies. So, for example, the Spanish bought from the Portuguese and the Portuguese had many of their shipment stations in Angola and Mozambique and most of the people they kidnapped and traded were from those two regions. In America, the British took them from different places along the African West Coast that changed with time, So it’s a different history. It’s been studied a lot among African-Americans, but it’s a different history. You wouldn’t expect the ancestry to be the same. So that’s an argument too.

Have you begun to think about the clinical implications of studying these populations? And have you talked to them about why so many people have high blood pressure, diabetes, and those sorts of issues?

Yeah, so there are two aspects. One reason I got interested is because I started hearing, by talking to people and reading, that there’s a lot of anemia in these places. So that is something that I want to know and I can learn from genetics: if this anemia is a predisposition. The sickle cell anemia, it’s protective against malaria and if you have mild anemia, you’re protected against getting malaria. I was curious to hear if the anemia that’s been observed in these regions could be related to sickle cell, as opposed to just not having good food with enough iron. So that was the first clinical aspect that I wanted to address.

And then I am also very interested in the skin pigmentation piece. When I was there, I collected the skin pigmentation data, because that also has implications on certain things, like predispositions for skin cancer (because the color of your skin determines how much UV you filter, and also if you are more or less likely to get skin cancer). So that’s another aspect I’m researching.

What are the clinics like in the communities you visited, and how do you interact with clinicians and doctors?

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There are not many there. Like in Oaxaca, for example, many people saw us and thought we were medical doctors and they would come and say, “I have this pain here,” “I feel bad in the mornings.” They wanted advice on their health and we had to say, “No sir, we can’t.” But there is very poor health there, and that was pretty sad to see.

Also, in the second fieldwork I did, there was a breakout of the chikungunya virus and that was really bad. In Oaxaca, some people had it, but in Guerrero, almost everyone had it. It’s a virus that is transmitted by a mosquito, so many people were sick and that’s a very painful disease. It’s like a very bad flu, but with a lot of joint pain and rashes. Many people came to us and said they had it, or they had had it recently and they were still in pain. I wished I could something about that, and that was a bit frustrating.

But then in Veracruz, we were super lucky to have on our team a medical doctor, Cesar, who came with us. That was great because, as we were measuring the hemoglobin, whenever we would find a low value we would ask Cesar to talk to these people and give them some advice. The people who came to us with pain, we could direct to Cesar and that was less frustrating than in Guerrero. And people really appreciated having someone to talk to about how they feel, because they don’t normally have much access to healthcare services.

So even though you’re not technically a clinician, are you able to give results back to the communities, say about a predisposition, and direct them to a doctor or anything like that? Can you do any amount of genetic counseling when you are out in the field?

I don’t think I would, at this stage, because they are admixed populations and most of the association studies are not based on people with African or indigenous ancestry. They are mostly done on people with white ancestry. And then in terms of monogenic diseases, I couldn’t feel comfortable giving those kinds of results.

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But what I can do and what they really liked is when we were measuring hemoglobin with a portable device and we were giving their results back to them that minute. So we would take a droplet of blood and measure their hemoglobin and say you’re ok or you’re low. And we would gather the people with low values and give a talk about what they can do to increase their levels. In Oaxaca, we had Silvia, a nutritionist who lives in the area, with us. So she could tell them what food sources found in the area are good for them. In Veracruz, Cesar could tell people what they can do, and for overweight people, why that can be dangerous. But that is the extent of the clinical advice that I feel comfortable giving.

So what’s next for you?

I’m flying to Mexico in a few hours (laughs). I’m starting a new position in Mexico, and it’s the National Autonomous University, the same university where I did my undergraduate studies. I’m excited! I know it’s going to be very challenging; it’s not going to be easy, because science policy in Mexico is very different than in the States or in Denmark, where I did my PhD. There are less resources, there’s a lot more bureaucracy, we have to do a lot ourselves, and you have to secure your own funding starting on day one. That’s going to be challenging, but I also like the idea of being closer to my fieldwork, and interacting with other Mexican scientists who are there (like Karla and Andres).

Are you excited about mentoring other grad students and postdocs who are coming up in Mexico?

Yes, definitely. I like teaching and I like to give advice to people, especially Mexicans who may be afraid of going abroad. I would basically like to have people from this community doing research on themselves.

What do you see as the role of Stanford CEHG, moving forward?

I really like CEHG. They have been super supportive of my projects. I think that the role of CEHG is just making our lives easier by giving us resources to fund our research, and giving us every tool we need to do our job, which is doing research, and not worrying about anything else.

Fellows Feature: Chris DeBoever

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Chris DeBoever is a CEHG postdoctoral fellow in the labs of Carlos Bustamante and Manuel Rivas. He is a graduate of Harvey Mudd College (BS, Mathematical Biology) and the University of California San Diego (PhD, Bioinformatics and Systems Biology). Chris uses genomics approaches to investigate the genetics of complex phenotypes and diseases in humans.

Can you tell us a bit about yourself, personally and professionally? 

I’m a postdoctoral researcher working with Drs. Carlos Bustamante and Manuel Rivas. I grew up in Orange County and have spent a lot of time exploring the wilderness in California, especially the deserts and mountains of Southern California. I completed a B.S. in Mathematical Biology at Harvey Mudd College and a PhD in Bioinformatics and Systems Biology at UC San Diego with Kelly Frazer. My PhD focused on the genetic regulation of gene expression and splicing in both cancer and stem cells. I also have an interest in public policy and research ethics, stemming from my time at Harvey Mudd, that I was able to explore a bit during my PhD, which included a trip to China as part of a delegation representing the AAAS. I enjoy playing and listening to music, camping, and traveling. After defending my PhD in May, I took a few months off to travel to Thailand and Europe before starting at Stanford in October.

Can you tell us about your current research and what you want to achieve with it? 

My research is focused on investigating the role of genetic variation in human disease and other phenotypes. I am approaching this problem by developing statistical methods and applying them to data from large biobank and genetic association studies. As the cost of sequencing and genotyping continues to decrease, we are going to have access to much more genetic data than ever before. However, our ability to obtain genetic data is outpacing our ability to recruit and methodically phenotype study participants. Instead, we will look to mining data from electronic health records, surveys, or even phones or wearables to gather phenotypic information that we can use in concert with genetic information for exploring the genetic factors that affect various phenotypes. I am working with data from projects like the NHGRI’s Genome Sequencing Program and the UK Biobank, which are collecting genetic data at a scale much larger than previous efforts. I am developing methods using these data sets that will be useful as we move toward even wider adoption of genotyping and sequencing.

Besides using genetic information and phenotype data from healthcare records to conduct research on the genetic causes of disease, I am also interested in feeding back results into the healthcare system. For example, we can construct genetic risk models for different diseases and see whether that information is useful in identifying people that have increased risk for disease. I think that the efforts to study the genetics of disease and integrate genetic information in the clinic are complimentary. For instance, we can use genetic risk models to identify people who have a high risk for disease but who are in fact healthy. It may be that these people have a protective genetic variant that protects them from disease. These types of variants can be really useful for identifying drug targets. We can also use this information to update our risk models. I am excited to see what we will be able to learn about how genetics contributes to disease risk over the next few years.

How did you end up at Stanford? What first got you interested in genetics and science?

I went to college thinking that I wanted to study math or physics. However, I took a required introductory biology course taught by David Asai (now at HHMI) and Stephen Adolph that really piqued my interest in biology. This was in 2007, so next-generation sequencing was just emerging, and it seemed like an exciting time in computational biology. I remember thinking that the field seemed like the “wild west,” because there was so much opportunity to investigate questions that had been difficult to look at in the past. I enjoyed my computer science classes as well, so computational biology seemed like a natural fit. I did research in college with Eliot Bush and really enjoyed it, so I decided I’d like to continue on to a PhD.

What are your future plans? 

I am hoping to apply for faculty positions and start my own laboratory following my postdoc. I enjoy doing science and exploring questions that we don’t yet know the answers to. I also enjoy teaching and mentoring, so I look forward to working with my own trainees. I’d like to be involved with industry at some level as well. As I mentioned above, I think that there are a lot of interesting problems related to how we implement genetics and genomics in clinical care, and some of those questions are best approached by partnering with companies, hospitals, insurers, and other healthcare stakeholders.

Tell us what you do when you aren’t working on research. Do you have hobbies? Special talents? Other passions besides science? 

I’ve played guitar for the last 10 years or so, and I enjoyed listening to many different types of music and discovering new artists. I enjoy recreational mathematics and reading. I love to sneak in an online course here or there about subjects outside of my research to continue learning about new areas.

Were there specific people in particular to whom you would attribute your professional success?

I’ve had a lot of supporters over the years that I owe thanks to. My family has been very supportive and I’ve certainly had many great teachers and professors. My high school math teacher, Barbara De Roes, was really great at encouraging my interest in math. I was privileged to receive an amazing undergraduate education at Harvey Mudd College. Mudd professors are very dedicated to teaching and provide a great environment for undergraduate research. I also really enjoyed my PhD with Kelly Frazer at UCSD; we had the complimentary strengths and points of view that you really want for a good mentor-mentee relationship.

What advice would you offer to other grad students or postdocs who are considering pursuing a similar educational and career path as you? 

I’d suggest taking a lot of math, especially the stuff that some of us don’t get in high school. Linear algebra, probability, and statistics play an outsized role in genetics (and many other fields). Fluency in these areas is really useful.

Similarly, start coding early. Hack together projects, even if they don’t have anything to do with science or academics. I’ve learned a lot about how to code and how to manage a codebase through little pet projects. As a computational scientist, you often act as software developer, tester, and maintainer, so it’s important to be able to do those things effectively so you have time to devote to the scientific questions.

Can you speak a bit to the role you see CEHG playing on Stanford campus?

Genetics is a very interdisciplinary field. The problems that I am interested in exist at the intersection of biology, computer science, and statistics, so it is crucial that I take interdisciplinary approaches. This often means communicating with people in other laboratories or fields to share expertise and gain knowledge. Stanford is a very collaborative place, and CEHG helps to facilitate those collaborations. There is such a wide variety of research going on amongst CEHG fellows and associated labs that it’s easy to find someone to chat about a problem you’re facing in your research.

 

Scientific American interview with Marcus Feldman!

mwf_outsideCLICK HERE to read a current Scientific American interview on “The Mathematics of Evolution” with CEHG Co-Founding Director, Dr. Marcus Feldman.

“Feldman’s openness to unexpected lines of thinking has allowed him to carve out a contrarian niche in a field where established ideas typically rule the day. Along with a group of similarly unorthodox colleagues, Feldman has developed a proposal called the extended evolutionary synthesis (EES). The EES argues that while the existing framework of evolutionary theory, known as the “modern synthesis,” is basically solid, it needs to be expanded to account for newly recognized drivers of evolution. One such driver is epigenetics — gene-expression changes that stem from exposure to, say, pesticides. While these epigenetic changes are not encoded in an organism’s genes, they do give rise to physical and behavioral differences that natural selection can act upon…”

 

 

Fellows Feature: Yoav Ram

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Yoav Ram (http://www.yoavram.com) is a CEHG postdoctoral fellow in the lab of Marcus W. Feldman. He is a graduate of Tel-Aviv University (PhD, Theoretical & Computational Biology). His research uses mathematical models and computer simulations to study the evolution of the genetic system, including the evolution of the rates of mutation, recombination, and mis-segregation and their dependence on stress and fitness.

Can you tell us a bit about yourself, personally and professionally? 

I grew up in Herzliya, a suburb of Tel-Aviv, and lived most of my life in the Israeli coastal plain between Tel-Aviv and Haifa, except for a couple of years I lived in Kibbutz Lotan, the southern Arava Valley, working in permaculture. I have three kids, ages 6, 3 and 6 months: my first son was born when I finished my undergraduate degree in Math and Biology; my baby daughter was born on my 33rd birthday, a couple of months after submitting my PhD thesis.

Why did you become a scientist? Did you want to be a scientist as a child?

I wanted to be a scientist since I was very young: I remember reading encyclopedias, and trying to figure if the horizon was straight or curved when I was 7 or 8. My grandfather was a chemical engineer (he even published in Nature in 1944!!) and a huge influence. In middle school, I was interested in astronomy and astrophysics after reading Hawking’s “A Brief History of Time.” In the army, I learned math, stats, and programming, and afterwards it was clear to me that I wanted to do quantitative research. I gravitated towards studying Biology while experiencing nature in Nepal and reading Dawkins’ “The Selfish Gene.” I took an “Intro to Evolution” course in my first year as an undergrad (taught by Prof. Lotem), and my mind was blown. The day after the final exam, I started a research project with Prof. Lilach Hadany. That was almost nine years ago…

Can you tell us about your current research and what you hope to achieve with it? Why is your research important? 

During my PhD, I used mathematical models and computer simulations to study the evolution of stress-induced mutagenesis – when individuals under stress increase their mutation rates. This is a common phenomenon in bacteria, and evidence suggests that it is also common in many eukaryote species, from yeast to human cancer cells. I was able to show that stress-induced mutagenesis can be favored by natural selection due to the beneficial mutations it generates, both in changing and constant environments, and that it increases the rate of complex adaptation without jeopardizing the population mean fitness – therefore breaking the evolutionary trade-off between adaptability and adaptedness. These results have important consequences for various aspects of biology, because mutation is such a fundamental force in evolution. But ultimately, I think that my research contributes to our changing understanding of mutation, and specifically, that mutation is more likely to occur in maladapted individuals – exactly the individuals that stand the most to gain from mutating.

Over the past two years, I focused on a different project, which gave me an opportunity to do experiments and learn new technical skills. Many microbiologists find that measuring microbial growth in a mixed culture is laborious and expensive, and even more so in non-model organisms. To mitigate this problem, I developed Curveball, a new method for predicting microbial growth in a mixed culture solely from growth curve data. I also validated this new method using experiments with bacteria. I hope that Curveball will be used by microbiologists and evolutionary biologists and that it will help bridge the gap between theoretical and experimental evolutionary biology.

Were there people (or one person) in particular to whom you would attribute your professional success? 

I worked for almost nine years at the Hadany Lab in Tel-Aviv University. Prof. Lilach Hadany is an amazing advisor and an inspiring researcher. It has been a daily privilege to study and work in the supportive and challenging environment she provided. The lab is very diverse, combining both experimentalists and theoreticians with different skill sets, working on a large variety of problems. A good example is the set of organisms being studied in the lab: bacteria, yeast, ants, plants – including cacti, tomatoes, and flowers – and digital organisms.

What are your future plans? Where do you see yourself professionally in the next 5 or 10 years?

My main scientific interest is developing models for describing and predicting evolutionary dynamics. My goal is to have my own lab in Israel, combining mathematical and computer modeling with microbial experimental evolution. I want to continue studying the evolution of the processes that generate genetic variance. In addition, I want to better understand the relationships between ecology and evolution.

CEHG’s core values include “interdisciplinary research” and “collaboration.” Can you speak to the ways your work has embodied these values? How do these values align with your own approach to science?

I’m an interdisciplinary and DIY type of person, in both my personal and work life. I am interested in the integration between theoretical and experimental evolutionary biology and I believe that such integration requires interdisciplinary research and collaboration between “wet” and “dry” biology.

The Hadany Lab is a good environment for collaborations between “dry” and “wet” biologists. I had the chance to sit through many “wet biology” seminars and helped on several “wet” projects by doing statistical analysis, dynamic modeling, and image analysis. In addition, my main research project during the past two years – on predicting results of competition experiments – was an opportunity to combine math, stats, programming, and microbiology, and to “get my hands dirty” doing experiments with bacteria and yeast.

What advice would you offer to other grad students or postdocs who are considering pursuing a similar educational and career path as you? 

  1. “Don’t ever let somebody tell you you can’t do something” (The Pursuit of Happyness, 2006).

  2. Work-life balance is important: most people can’t work 24/7 (but see (1)), and reading fiction when you should be reading papers or taking a walk when you should be in front of a computer is OK.

  3. If you don’t know what Impostor syndrome is, then read about it.

  4. If you see a mathematical result that you don’t understand, try to derive it on your own before looking for the original derivation. It builds intuition and skill and sometimes can lead to new findings.

Tell us what you do when you aren’t working on research and why. Do you have hobbies? Special talents? Other passions besides science?

I like cooking, hiking, home-improvement (I used to build mud huts and I like working with wood), playing with my kids, and watching NBA (I’m a Lakers fan). 

 

Fellows Feature: Sharon Greenblum

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Sharon Greenblum is a CEHG postdoctoral fellow in the lab of Dmitri Petrov. She is a graduate of Northwestern University (BS, Biomedical Engineering) and the University of Washington (PhD, Genome Sciences). Her research focuses on studying rapid adaptation in response to natural environmental and ecological change, primarily using Drosophila melanogaster as a model organism.

Can you tell us a bit about yourself, personally and professionally? 

I am a postdoc in Dmitri Petrov’s lab, currently studying the dynamics of rapid adaptation. I grew up in Maryland, but have lived in quite a few places since then, including Chicago, Copenhagen, Washington DC, Tel Aviv, and Seattle.

My path through science has been a bit all over the map as well. I started out studying biomedical engineering as an undergrad at Northwestern University, interested especially in the mechanics of the human body, and what a model of how a knee bends or how a lung inflates can tell us about the course of human history and the challenges our species has found solutions to over time.

My junior year of college, eager to escape another brutal Chicago winter, I decided to study abroad. Though the basis of that plan backfired slightly – Copenhagen in January is no springtime in Paris – academically, it was a real turning point. I completed a course in Bioinformatics, which got me started on the more molecular track I’ve followed ever since. After college, I did a two-year fellowship at the National Institutes of Health, working in a bioinformatics lab studying the molecular pathways implicated in different cancer subtypes. I decided then that I would really benefit from a solid foundation in genetics, so I joined the Genome Sciences Dept. at the University of Washington for my PhD. There too, I took a leap into something new; I joined the lab of a brand new professor studying something I’d never heard of – the human microbiome. It was really exciting being part of such a fledgling field, especially one that allowed me to combine my interest in coming up with new bioinformatic techniques with my passion for understanding the complex forces that have shaped human health and history.

Why did you become a scientist? Did you want to be a scientist as a child? (tell a story)

I didn’t always want to be a scientist. When I was little (and I have the big scrawly handwritten essays to prove it), I wanted to be a librarian. At the ripe old age of eight, I was picturing myself with little pince-nez glasses and pearls. Then it was a journalist, a reporter on the front lines. Then a CIA agent. Then a National Geographic Explorer-in-Residence. Truth be told, I still want to be all of these things. Very much so. Science is the best way I know of to combine these dreams. The common thread through all of these is a desire to get beneath the surface, to understand why things work, to explore, and to ask instead of accept.

Can you tell us about your current research and what you want to achieve with it? Why is your research important? 

In Dmitri’s lab, I’m focusing on developing bioinformatics frameworks for a new way of studying evolution – one that lets us measure adaptation in real time, in real conditions, with realistic metazoan populations. The approach has been termed ‘evolve and resequence,’ and it’s an incredibly exciting step for the field of evolutionary biology. To make the most of it though, we still need to figure out the best ways to obtain the most accurate measurements, and identify meaningful and robust adaptive signatures from large-scale pooled genomic samples taken at multiple timepoints.

More specifically, we’re trying to understand how populations of fruit flies respond to changing environmental conditions over the course of a single summer. From collecting samples of wild fruit fly populations at different timepoints, Dmitri and his colleagues have found evidence that an impressive amount of genomic adaptation may be occurring within populations even at these short timescales, enabling successive fruit fly generations to become better at metabolizing resources quickly when food is abundant, for example, or surviving longer in times of food scarcity. Much of this adaptation appears to be from standing variation – alleles already found in the population that rise and fall in frequency over time.

In general, I’m really excited by the idea that experiments can move beyond the laboratory, and that we can incorporate the tempo of real life. My interest is in developing experimental and bioinformatic frameworks for modeling evolutionary dynamics derived from real biological data. I think that a deeper understanding of how populations adapt may fundamentally change our view of way evolution proceeds, and our assumptions about the timescales that are most influential.

What are your future plans?

I’d love to continue understanding evolution and the processes that govern adaptation at the molecular scale, in whatever capacity I can. More specifically, I’m hoping to spend the next few years gaining a clearer picture of evolutionary dynamics in both host and microbial contexts, so that I will be well-positioned to begin incorporating these processes into a predictive model of host-microbiome co-evolution.

This could mean running my own academic lab, but I also think that the traditional divides between academia, industry, and even the arts may continue to blur. At some point in the future, I’d love to be part of an inter-disciplinary team focused on putting the pieces together.

Were there people in particular to whom you would attribute your professional success? What is it like working with your current lab advisor and his lab?  

I owe a lot of my current research perspective to my PhD adviser, Elhanan Borenstein. When I started grad school, I was almost exclusively interested in human genetics, but had only very vague ideas about what part I wanted to study. I definitely never expected to end up studying bacteria. But when I heard Elhanan present his research ideas to the department for the first time, I was really inspired by how he was thinking outside the box, trying to tackle really ambitious questions with unique data analysis approaches, and borrowing tried and true systems biology tools but applying them in a completely new realm. A colleague and I were the very first students to join the lab, and we got invaluable training in how to think critically and creatively. I think that really shaped how I saw science – that it’s not just about what you know, or what you can measure, but the context you use to interpret it.

I’ve been at Stanford for almost a year, and working with Dmitri has definitely inspired me as well, in complementary ways. Dmitri embodies an enthusiasm for science and academic inquiry that I have yet to see matched in anyone else. He is sharp, forward-thinking, and importantly, has a never-ending drive to share the ideas that inspire him, and turn them into reality. It’s abundantly clear that Dmitri loves what he does. The ‘fun’ part of science is what keeps me going, and Dmitri provides an admirable model of how keep this at the forefront while maintaining exceptional scientific rigor and integrity.

Can you speak a bit to the role you see CEHG playing on Stanford campus?

I think CEHG is a wonderful and important organization to have on campus. I’m a big believer in the power of being able to tackle a problem from multiple perspectives, and I think CEHG offers a means to gain deeper insight into fundamental evolutionary questions by uniting labs with disparate approaches but the same goals at heart. I think one of the biggest challenges is finding ways to facilitate communication between fields with very different vocabularies (both literally and conceptually), and CEHG may provide a training ground for scientists who are better prepared in this regard going forward.

I also think that forming an umbrella organization focused on big-picture questions (rather than specific approaches) opens the door for less traditional perspectives as well. I’ve been working with CEHG to form an Arts interest group to try to look at how the questions CEHG labs focus on are reflected in and informed by art and design. It’s been really fun and fascinating so far, and I don’t think I would have had the opportunity to do this at most other institutions!

What advice would you offer to other grad students or postdocs who are considering pursuing a similar educational and career path as you? 

I’d advise other grad students to listen closely to their instincts, and be open to new possibilities. The field of genetics is so broad, and is changing so rapidly, that what seems important one day may change by the next, so concentrating too narrowly may mean you miss out on the more exciting developments. I’d advise students to try not to be intimidated by how much there is to know and keep up with though, but trust their capacity to learn and synthesize.

Trust also that every experience can be beneficial – a background made up of what interests you will give you a unique perspective going forward. Mostly, I’d advise students to just keep on going, to take opportunities to learn something new and have fun with it.