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.

Fellows Feature: Zach Zappala

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Zach Zappala is a CEHG graduate fellow in the lab of Stephen Montgomery. He is a graduate of The College of New Jersey (BS, Biology and Computer Science). His research focuses on statistical methods for identifying the genetic basis of rare complex traits.

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

I’m a 5th year PhD student in Genetics. I grew up (and went to college) in New Jersey before moving to California. When I was an undergraduate, I majored in biology and computer science; I have been interested in using computational methods to solve biological problems ever since I was 17 and first started working in a research lab. During college, I spent a summer living in Tokyo while taking Japanese language classes.

I came to Stanford straight after I completed my undergraduate degree, and have really enjoyed living in northern California. I like to travel and enjoy hiking around the Bay Area. I especially like skiing in Tahoe during the winter, and try to get outdoors as much as possible.

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

When I was in high school, I really liked working with computers, writing code, and coming up with novel solutions for problems I encountered. I was obligated to do a scientific internship when I was 17, and I enjoyed applying all of my computational skills to the genetics problems I was working on. As an undergrad, I decided that I would like to continue on and get a PhD and I continued doing research (although most of my work was at the bench!).

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

My current research has been focused on developing methods that can identify the genetic basis of extreme traits (either disease status or some other human trait). I have been trying to do this for mutations that impact gene regulation, which is generally pretty difficult for rare mutations. I’ve spent a lot of time studying a cohort of families from Sardinia, Italy, where my closest collaborators are from.

The island of Sardinia is particularly interesting for genetic studies because, while it was first inhabited thousands of years ago, it has remained relatively genetically isolated. As a result, the distribution of mutations on the island is unique relative to geographically close regions due to drift and selection. Additionally, Sardinians have elevated risks for autoimmune disorders like type 1 diabetes and multiple sclerosis, and they have historically experienced significant exposure to malaria until its rather recent eradication. By looking at families, we are better able to capture the effect of rare mutations that are transmitted from parents to children, and can use these events to understand the genetic mechanisms underlying gene regulation and disease risk in these individuals.

Additionally, we are now working to bring these methods into the clinic in order to understand Mendelian diseases that result from non-coding variation. Such scenarios are difficult to approach with exome and whole genome sequencing. As a result, only about 30% of rare disorders are “diagnosed” – meaning that the causal mutation (or affected gene) has been successfully identified. By studying gene expression in rare disease patients, we are hoping to increase the diagnostic success rate for clinical genome centers and improve the care and treatment of these patients.

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

There are so many people that have been a huge part of any successes I’ve achieved – all of my mentors and advisors, collaborators, and lab mates have played an integral role. In our current lab, several of us often work very closely together on a few projects, helping out where our own particular expertise applies.

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

I think that CEHG plays a unique role for the scientific community here at Stanford – for one, it brings together labs in different departments that, while separated on paper (and on campus), work and think about the same kinds of things all the time. Having a formal Center through which these labs can interact loops these people together, and is better for everyone.

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

Looking back, I think I would have benefited from taking some time off between my undergraduate degree and graduate school – while this isn’t necessarily true for everyone, I had trouble adjusting to the different kinds of academic pressures that exist in graduate school. However, I have no regrets – doing a PhD has been an incredibly fun and rewarding experience, and I have met some of the most incredibly interesting people I know here at Stanford and at conferences I’ve traveled to.

 

Fellows Feature: Katie Solari

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Katie Solari is a CEHG predoctoral fellow in the lab of Elizabeth Hadly. She is a graduate of UC Berkeley (BA, Integrative Biology). Katie’s research investigates the mechanisms underlying high-altitude hypoxia tolerance, focusing on Asian pika species (small mammals related to rabbits, who serve as the inspiration for pikachu). 

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

I grew up less than 10 miles from Stanford campus, in Redwood City. I went to Berkeley for my undergrad, but I didn’t go straight into graduate school. I spent one year working for AmeriCorps NCCC, where I mainly did construction in New Orleans, rebuilding after Hurricane Katrina – this was one of the best experiences of my life. I also taught students with learning differences at a Bay Area high school for two years, and really enjoyed that teaching experience.

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

As a kid I was obsessed with animals, every story I wrote or picture I drew was of one of my pets (we had a dog, cat, and a tortoise). My Dad is a high school biology teacher, so growing up we always had a microscope at home that I loved to play with and look at microorganisms in pond water or insects from the backyard.

After undergrad, I was given the opportunity to travel to Tanzania for a summer to teach English and Biology. While I was there, I was able to go to Serengeti National Park and the Ngorongoro Conservation area for three days. The wildlife was unlike anything I had ever imagined. Witnessing the beauty of these animals in their natural habitat and thinking about all of the Anthropogenic pressures threatening their existence, and all that we still have to learn from them, sealed the deal for me. I knew I wanted to do research to learn more about the wildlife around us and to hopefully play a role in its maintenance.

Can you tell us about your current research and why your research is important?

Specifically, my dissertation work has been focused on investigating the mechanisms underlying high-altitude hypoxia-tolerance in pikas (small mammals related to rabbits). However, at the heart of this work is a desire to better understand how our world will change with continued climate change and how we might be able to mitigate these impacts in some way.

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Ochotona roylei in Spiti Valley, Himachal Pradesh, India. 2013 photo courtesy of Katie Solari.

There are about 30 pika species, two are found in North American and the others are all in Asia. Pikas are extremely heat-intolerant and, as such, are generally isolated in cool habitats at high elevations or high latitudes. In response to climate change, pikas in parts of the US and the Himalayas have been moving to higher elevations to escape the heat. Due to their thermal sensitivity and their relatively rapid range retraction, pikas have become an icon of climate change.

By assessing what mechanism pikas have at their disposal to deal with high-elevation hypoxia, I hope that we will be able to better assess which species and populations will be capable of living in the high elevation refugia that they are being forced into. Our findings so far indicate that high elevation pika species (such as those living in the Himalayas) have genetic adaptions to help them deal with hypoxic stress that are not present in lower elevation species. These findings suggest an elevational specialization of pika species, indicating that it may be hard for species to shift elevational ranges quickly in response to climate change. However, a study I conducted on a single population of pikas in the Indian Himalayas, along an elevation gradient (3600-5000m), indicates that plasticity in gene expression may also play a role in allowing pikas to shift elevations. This suggests that even though there are genetic adaptations playing a role in hypoxia-tolerance at the species level, plasticity in gene expression may also facilitate range movement at a finer scale.

Pikas are extremely important to their ecosystems, acting as both ecosystem engineers and keystone species. I hope that the more we learn about their ability to respond to climate change, the more likely it will be that we will be able to preserve them, and the services they provide their ecosystems, into the future.

Were there people (or one person) in particular to whom you would attribute your professional success? What is it like working with your current lab advisor and her lab?

Liz has been an amazing mentor to me over the past five years. She has helped me mature as a scientist, critical thinker, and collaborator. More than anything, she has shown amazing confidence in me and has given me the room to try to rise to every new challenge. Something I’m particularly grateful for is the incredible example Liz has set for how to take research out of academia and into the real world, in order to get closer to affecting real change. I believe that the current state of the world demands that researchers cross over into policy and action, and Liz has done an incredible job at exemplifying how to do that.

I have also had the privilege to work extensively with Dr. Uma Ramakrishnan, from the National Center for Biological Sciences in Bangalore, both here and in her lab in India. Uma has also set a great example for how to work toward merging science and policy so that what we learn can be translated into real world changes on a timescale that will keep pace with the rapidly progressing challenges that our world is facing. The way that both Liz and Uma think about environmental issues and the role that scientists can play in solving them have greatly impacted me and what I aspire to do after my PhD.

Courtney Wilson also had a pivotal impact on my decision to go to grad school to begin with. Courtney and I, best friends since preschool, both had similar aspirations after undergrad to work towards environmental betterment. After leaving undergrad, I didn’t know anyone in the academic world – Courtney was it. She was working at a lab in Cornell and was my vital connection to academia. She helped me get access to the scientific literature for my applications, introduced me to graduate students doing conservation research, and, more than anything, was having all of the same concerns about biting off grad school and was the exact sounding board that I needed to decide that grad school was the right choice for me. When I started my PhD at Stanford, Courtney started her Master’s at the School of Natural Resource and the Environment at the University of Michigan and went on to begin her PhD there. The world was robbed of what Courtney had to offer when she tragically passed away in the first month of her PhD program, but her contagious drive and passion is still helping me, along with many others, work towards a shared goal of environmental improvement.

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Katie Solari conducting fieldwork in Spiti Valley, Himachal Pradesh, India. 2013 photo courtesy of Ania Wrona. 

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

I mainly just want to do something that will move us, however little, towards responding to the challenges of our time in an effective way. I’m open to any opportunity to work towards preserving the organisms and ecosystems that we have and/or mitigating climate change and its impacts.

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

Be prepared to experience 10 times as many failures as successes. Research always feels like an uphill battle. You can’t let rejections or failures get you down. You need to keep moving forward and see everything as a learning experience.

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

CEHG exemplifies the best parts of Stanford in that it facilitates innovative thinking in order to move science into new and exciting directions. CEHG funding opportunities allow students to use their imagination and take risks – a CEHG trainee research grant allowed me to initiate collaboration with the Minnesota Zoo in order to work with the only captive population of pikas in the world (held there).

Through the outreach group, CEHG also makes it a priority to reach out to the local community to share the love of science with local middle school and high school students. The types of opportunities that CEHG offers its students, as well as students in the local community, is what makes Stanford a place that fosters novel research and a general love for science.

Fellows Feature: Sebastien Boyer

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Sebastien Boyer is a CEHG postdoctoral fellow in the lab of Gavin Sherlock. He is a graduate of the University of Grenoble (MS, Physics) and earned his PhD  in the Laboratory for Interdisciplinary Physics at the University Grenoble (Physics for Life Sciences). His research focuses on yeast population (as a model organism) evolving in changing environments and, more particularly, on the effect of time scale and the randomness of those changes on adaptation. 

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

I am a French physicist interested in various problems found in biology and, more particularly these days, evolution. I was born and raised on a French island, named Reunion Island. It’s a tropical island in the middle of the Indian Ocean, known for it’s multi-ethnicity, world class waves, volcano and unique landscape. I spent most of my college time in Grenoble (Mainland France), and did a year exchange in Hong Kong.

I used to swim on a team for 17 years, but nowadays I am swimming and playing Water Polo for fun, here at Stanford. I used to travel a lot, from Mongolia to Tanzania through Norway (for example), and I am now very eager to discover California and the U.S., generally speaking.

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

I am a big fan of science fiction and have been since I was a child. As a child, I wanted to be an explorer, crossing the galaxies in fancy spaceships to discover new planets and life forms. This somehow led me to physics: quantum mechanics and relativity were, for me, real world science fiction.

In Hong Kong, I had the chance to attend a talk of Bob Austin’s about antibiotics resistance, and he was talking like a physicist: individuals were hopping from one point to another in a more or less rugged fitness landscape. Sometimes they were randomly diffusing, and other times, they were driven toward an optimal. I realized that physicists might have relevant things to say about biology and evolution.

From there, I did a PhD in the field of protein evolution and, to some extant, immunology. For a postdoc, I wanted to go from the bottom up and work with eukaryote to get into the genetics of evolution and not only its statistics. I got interested in the work of the Sherlock lab because the barcoding technology they developed actually allows you to have access to the statistics and genetics of evolving yeast populations.

Can you tell us about your current research and what you want to achieve with it? You could start by listing 3 words you think best represent or embody your research.

Evolution, changing environments, yeast.

I am interested in the influence of changes in the selective environment that a population (of yeast, as a model organism) can encounter. More specifically, I am interested in the influence of the time scales on those changes (long enough to trigger adaptation in the different environments or shorter than that).

Similarly, I also look at the effects of predictable changes vs random changes on the evolution of those populations. I want to see the effects of those changes in terms of dynamics, statistics and genetics. For example, I would like to see the emergence of different genetic strategies from different types of environmental changes. My work is mainly experimental, even though I have been coding (python) quite a lot so far, for future sequencing analysis. I also coded an algorithm reproducing in silico the experiment I had in mind; it helped me a lot to design it actually.

In nature, environments are changing and populations have to cope with that. Understanding to what extent a population adapted to one environment can adapt to another one is crucial. Questions about a changing environment, the time scale of the changes or its degree of randomness are, for example, directly linked to antibiotic resistance for bacteria or drug resistance in cancer.

Were there people (or one person) in particular to whom you would attribute your professional success? What is it like working with your current lab advisor and his/her lab? 

My mother for teaching me how to read, and my father for introducing me to science fiction. My math teacher in “prepa” (cram school for engineering school) for teaching me, the hard way, two really important life/academic lessons : 1) You can and will fail and there is nothing to be afraid of there; 2) When faced with a difficult problem, think hard but don’t get stuck. Instead, get started, even if your first action seems useless; for example, just rewrite what is known about the problem. A journey of a thousand miles begins with a single step.

The lab is used to working with physicists through collaboration with the Fisher and Petrov labs. I took some time to actually build this project. Gavin gave me this time and was really enthusiastic about the ideas I was bringing. It’s really nice to be trusted that way in the development of a new project. Even though I am alone in this project, I have the help of Lucas Herissant for experimental expertise and Jamie Blundell and Atish Agarwala for the theoretical counterpart.

What are your future plans? 

I would like to get a tenure position in a university somewhere in Asia or Oceania, still working in evolution and probably expanding my research horizons into other fields of biophysics, like neuroscience for example.

Can you speak a bit to the role you see CEHG playing on Stanford campus? CEHG’s core values include “interdisciplinary research” and “collaboration.” How do these values align with your own approach to science?

CEHG is one of the main promotors of interdisciplinarity in the field of genetics and genomics on Stanford campus. It acts like a hub, giving the opportunity for experts from different fields to interact.

Often, during my PhD, we ended up talking about our research with the same small group of people, all physicists, although our research could influence or be influenced by other fields like immunology, protein design etc… We were lacking a community that would bring us together, and that is really what CEHG does I think.

As a physicist and evolutionary biologist who wants to explore evolution in the framework of genetics, it is obvious how my values align with those of CEHG.

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

Just go for it. By working in an interdisciplinary environment, you never stop to learn and can get introduced to problems and experiments you never though of. One week, I learn in a journal club that some neurons are activated into a spatial pattern, and the week after, I am listening to an awesome talk about multicellular emergence. Science needs more and more interactions between specialists from different fields and people who can actually make the links between those different communities.

 

 

Fellows Feature: Ziyue Gao

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Ziyue Gao is a CEHG postdoctoral fellow in the lab of Dr. Jonathan Pritchard. She received her Bachelor’s Degree in Biological Sciences and a second degree in Economics from Tsinghua University in China. She then did her Ph.D study in genetics at the University of Chicago, working with Dr. Molly Przeworski. Her research focuses on understanding the roles of mutation and natural selection in shaping the genetic variation pattern in human populations, particularly their impact on the prevalence and distribution of disease-associated mutations.

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

I started my postdoc in Jonathan Pritchard’s lab in September 2015, after finishing a PhD in genetics at the University of Chicago. I was a graduate student in Molly Przeworski’s lab, and we studied the impact of balancing selection on maintaining genetic diversity in primates and the burden of recessive lethal mutations in human.

A bit of background about myself: I was born and raised in Beijing, China. My childhood and teenage years were pretty boring: the kindergarten, elementary school, middle school, and high school I went to were all within a 5km radius circle around home, and I attended a university where my grandfather and my mother worked. I was so glad that this routine finally ended with my journey to Chicago for graduate study.

What have you perceived to be the differences between the US and your home country? Have you enjoyed your time at Stanford?

The US values diversity and work-life balance much more than my home country does. I have benefited a lot from these differences in my career and personal developments. I feel extremely lucky to be able to work and study at Stanford.

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

Together with Jonathan [Pritchard] and Emily Glassberg, a grad student in our lab, I’m currently studying the selection pressures on gene expression levels. Expression changes are long hypothesized to drive a great amount of phenotypic differences between species and among individuals, but whether or not and to what extent gene expression is under evolutionary constraints is largely unknown.

We try to tackle this question by utilizing results from recent genome-wide analyses of gene expression. By comparing the joint distribution of allele frequency and effect size of identified expression-altering variants across different groups of genes, we can infer whether the expression levels of these groups are under different levels of evolutionary constraints. We also develop a likelihood-based method to estimate the overall proportion and average effect size of all regulatory sites for any given group of genes. Together, these analyses will bring new insights into the genetic architecture and evolutionary constraints on gene expression in humans.

What first got you interested in genetics and science?

In college, I was fascinated by the rigor of genetic analysis and the rapid development of molecular techniques, and I thought the quantitative nature of genetics would provide me a niche to combine my strength in mathematics and passion for life science.

Prior to joining the University of Chicago, I had never heard of the field “population genetics,” but after taking only two lessons taught by Dr. Dick Hudson, I decided to do a rotation in a population genetics lab. After a rotation in Molly’s lab, I was determined to devote my PhD (and hopefully my career) to research in population genetics.

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

There were, of course, many people that had great impacts on my career decisions, but I would like to especially thank two of them, Dick and Molly, for introducing me to the wonderful world of population genetics.

What is it like working with your current lab advisor and his/her lab? Do you have lab mates you work closely with on projects?

Working with Jonathan is a real pleasure. He is very flexible in terms of his working style— he can be as attentive and as hands-off as you need. This flexibility leads to higher work efficiency and more innovative ideas.

I also really enjoy being surrounded by my lab mates, who have the perfect composition of smartness, nerdiness, and fun. I learned a lot from them, especially from Emily, with whom I am currently working closely on studying selection on gene expression.

What are your professional plans for the next 5-10 years? 

My ambition is to get a position at a university, either in the US or in my home country. I also have passions for forensic science and science fiction, so don’t be surprised if you find me becoming a detective or a sci-fi writer 10 years later.

Do you have advice you would like to offer undergrads, grad students, and postdocs (thinking of) working in your field? 

For grad students, cherish your time in grad school: it is a great time (if not the best time) to learn some theory, build up skill sets, try bold ideas, and not worry much about progress.

Research is not a “linear” process. It is especially slow and challenging at the beginning.

Sometimes we are stuck on a project for months or even years with no good/trustable results, but it doesn’t mean we achieve nothing — we learn a lot from the quests, setbacks and even failures. Grad school is such a rare opportunity when one can focus on learning and the cost of failure is very low.

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

The Evolgenome seminar series is one of the great things that CEHG offers. It enables me to learn new knowledge and perspectives from others’ research on a regular basis. The annual CEHG symposium provides further opportunities to interact with speakers and audience members from on and off campus. I can see that these activities will facilitate the exchange of ideas and foster a lot of future collaborations.

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

I always have huge passions for movies and stage plays, but recently I’ve been spending a lot more time outdoors, training for a half-marathon. Other than the wonderful academic environment and opportunities at Stanford, I feel this new hobby is the best gift that the Bay Area gives to me.