Fellows Feature: Atish Agarwala

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Atish is a PhD student in Daniel Fisher’s group in Stanford’s Applied Physics department. His primary interest is in studying models of epistasis, and understanding how the statistics of “fitness landscapes” affect the speed and predictability of evolution. He also works at the intersection of evolution and ecology, trying to understand how co-evolutionary processes generate and maintain diversity in complex ecosystems.

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

I grew up in San Jose, a diverse city still near and dear to my heart. I’ve always been interested in math and science. I was influenced by my father’s job as an engineer, and my mother always pushed me to succeed academically. When I was 10 years old, I decided I wanted to be a theoretical physicist. For better or for worse, it stuck. I studied math and physics as an undergrad at Swarthmore College, outside of Philadelphia. I love that both fields begin with basic assumptions, and, with those alone, you can discover fundamental truths about the universe.

Near the end of undergrad, I became interested in quantitative biology. It seemed like a more open and underdeveloped field compared to modern physics, which would give me a chance to make a big scientific impact. I applied to Stanford because it had strong research groups in theoretical biology (and because I was tired of being cold in Pennsylvania!). I eventually joined Daniel Fisher’s group, where I now study various aspects of evolution.

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

I use a combination of modeling, simulation, and data analysis to understand what determines the tempo and character of evolution in different scenarios. One of my main projects has been to analyze how epistasis (interaction between mutations) affects evolution. For example, a pair of mutations might do nothing individually, but give benefits to an organism if both are present. Or, they could be beneficial individually, but harmful together. I used a combination of mathematical and computational approaches to show that the linked effects of mutations cause the statistics of future evolution to depend on the statistics of past evolution. My modeling suggests that picking up lots of weakly-beneficial mutations might be better in the long run than picking up a few big, advantageous ones.

Insights like these have practical importance. A quantitative understanding of evolution is critical to solve the most urgent issues in global health today. For example, choosing strategies to curtail antibiotic resistance requires knowledge of how resistances arise in the first place. Cancers require cells to pick up multiple mutations, the probability and timing of which depends on the interactions between them. The flu vaccine needs to be designed to stop next year’s strain of the virus, which requires prediction of which rare strains will be common in the future. Characterizing these complex systems requires theoretical understanding of how different evolutionary processes play off each other.

More recently, I’ve become interested in the intersection of evolution and ecology: what happens when different types of organisms are living together, interacting, and evolving all at once? These co-evolutionary scenarios are important in nature, and can have a very different flavor from evolution within a single population only. I’m currently working on understanding how diversity is stabilized within models of ecosystems, and I hope to branch out and study data from real ecosystems (either in the lab or the wild).

What’s the coolest thing about your work?

It’s exciting that many basic things about evolution are not known. Although there is a lot of great experimental work (enabled by amazing technological development), theory is far behind the data we can collect. It feels akin to what doing physics in the 1700s must have felt like: there is clearly structure in the world, but the overarching understanding still eludes us!

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

I owe a lot to the first physicist who I ever met: Dave Dorfan. Dave was then a professor at UC Santa Cruz who taught at a summer camp for high school students. At that camp, Dave taught me what being a physicist was all about: asking lots of questions, carefully refining them, and, even more carefully, testing them. I also learned two important facts about science: it was, in fact, fun, and also something I could make a career out of.

Dave continued to help me throughout my scientific journey. He was always available with advice about coursework and finding research internships. Dave was also the first person to suggest quantitative biology as an area that I should look into. Without him, I’d likely be in a more traditional subfield of physics.

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

I’ve always loved science. From an early age, I was fascinated by space. I wanted to be an astronaut, and I can still remember the glow-in-the-dark map of the solar system I had on my bedroom wall as a kid. In 5th grade, my teacher gave me a copy of A Brief History of Time. I tore through it. At the time, I didn’t understand most of the book, but, nevertheless, I was spellbound by the mysteries of the very microscopic and very macroscopic. I asked my teacher what job Stephen Hawking had, and he told me, “Well, I think he’s referred to as a theoretical physicist.” That day, I made up my mind to become one. Surprisingly, I stuck with it, and even more surprisingly, it panned out!

I hope to continue to do theory. I enjoy my work, in part because it aligns nicely with my skills and temperament. I’d love to run a research group in a few years’ time, with the freedom to set my own research directions as well as the ability to mentor students through the process of becoming a scientist.

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

In my mind, one of the biggest determiners of success in grad school is the people you work with. It’s important to find people who you find inspiring, who are fun to work with, and who have a vested interest in your success. Research is difficult enough without having to deal with people who you don’t mesh with.

My other piece of advice for those in the throes of a PhD is: academia is not the only path forward.. I strongly encourage PhD students to learn about and explore other options while they’re still in grad school. The non-academic path is often stigmatized, but it shouldn’t be. Of my friends who started grad school when I did, some of the happiest are those who left academia, either before or after finishing their PhD. Both paths are valid.

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

I’ve been fortunate enough to collaborate with the Petrov and Sherlock labs, both of which are heavily involved with the Center. I worked with scientists in both labs (especially CEHG Fellow-mate Yuping Li) to study the character of fitness gains in microbial experimental evolution. Combining their experimental expertise and my theory expertise, we designed experiments and analysis methods to tease apart the tradeoffs made by organisms evolving on short timescales. The type of work we did wouldn’t have been possible without both sides of the equation, and that collaboration has been one of the highlights of my PhD.

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’m into gaming, both board games and video games. I also play jazz flute with a group on campus.

My biggest non-scientific passion, however, is hockey. I play on the Stanford Club Ice Hockey team with both undergrad and grad students, and I’m involved in organizing team activities. My favorite moment on the team was when we played a game at the San Jose Sharks NHL arena. I’ve dreamed about what it would be like to play in my hometown team’s arena, but I never thought I’d actually get the chance!

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Fellows Feature: Monica Sanchez

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Monica Sanchez is a Postdoctoral Fellow in the Petrov lab (2017-now). She received her Ph.D in Molecular and Cellular Biology at the University of Washington. She is interested in studying the effect of genetic background differences on general mechanisms of evolvability and aims to understand how genetic and environmental interactions affect adaptation and complex traits.

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

I am originally from Albuquerque, New Mexico, where I attended the University of New Mexico. I studied biology and chemistry, and initially performed research in a biomedical engineering lab, where I designed low-cost diagnostic devices. As I took more advanced biology courses, I quickly became interested in genetics and joined a research program that allowed me to work in a yeast lab where I discovered the power of genomics. I became very interested in functional genomics, and I eventually joined a molecular and cellular biology PhD program at the University of Washington in the Department of Genome Sciences.

While at UW, I joined a lab that combines experimental evolution with genomic analysis to study the structure and function of genetic networks in yeast. I was very interested in understanding how different species of yeast adapt to a variety of different conditions and I am pursuing similar questions in evolutionary biology in my current postdoc position. I hope to understand adaptation in the context of ecology in order to gain a deeper understanding of general evolutionary processes.

Why did you become a scientist? What first attracted you to genetics and science?

I grew up in New Mexico in the Rio Grande Valley, where I would spend a lot of my childhood exploring the Bosque trails with my father.  I cherished the escape from the city in the wooded areas and I loved identifying new creatures during our visits. It was obvious to me that I wanted to grow up to become a scientist in order to discover new species and learn how they interact with their environment. Although I wasn’t exactly sure how to obtain such a profession, I always knew that I loved learning new things about biology and I would try my hardest to make that dream a reality.

Can you tell us about your current research and what you hope to achieve with it? What kind of responses have you gotten to your research/findings?

As a postdoctoral fellow in the Petrov lab, I am focused on two questions that specifically focus on the importance of genetic background on adaptation, using yeast as a model. In the first, I focus on the difference in the nature of adaptive mutations in haploids and diploids in terms of their molecular basis, distribution of fitness effects, and the distribution of dominance. I am also specifically interested in whether, as predicted, adaptive mutations in diploids are often not just partially dominant but also overdominant.

In the second, I attempt to test whether genetic background has any predictive effect on the ability of lineages to evolve over the long-term in a way that cannot be fully predicted from the patterns of adaptation over the short term.  To accomplish this, I incorporated a diverse set of barcode sequences to track natural isolates of yeast to test mutational spectrums in each natural isolate as well as in mixed communities. This strategy will allow me test how different compositions of competitors influence adaptive trajectories. The overall goal of this project is to determine generalizable rules of adaptation, which is important for understanding adaptive events involved in many human diseases such as cancer and pathogenic diseases.

The next steps in the process of discovery for my project would be to incorporate different elements from natural environments. For example, we can test more complex mixture of microbial species, different carbon sources, or the effects of spatial distributions on their adaptive potential, providing insight into their evolutionary history.

What is the coolest thing about your work?

The coolest aspect about my work is that it incorporates an element of what is actually seen in nature. Most microbes don’t grow in isolation, and if we study them as single cultures, we may be missing important evolutionary forces that are shaped when complex microbial communities are formed.

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

As an undergraduate, I participated in a research program directed by Dr. Maggi Werner-Washburne, who has made a tremendous impact on my success as a scientist. The mentorship and support I received from her was essential for me to navigate through graduate school applications, and a key part of why I decided to apply to graduate school. Dr. Werner-Washburne is inspiring and her mentoring resonated with me, allowing me to realize my own potential.

Furthermore, she urged me to perform research through a summer program with Dr. Jay Shendure at the University of Washington, where I discovered my passion for genomics. This experience influenced my decision to attend UW for graduate school, where I applied genomic approaches to evolutionary questions with Dr. Maitreya Dunham, who is an extremely supportive role model for women in science as well.

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

I would advise grad students or postdocs to think hard and think early about where they see themselves in the future. It’s easy to get caught in the routine of everyday life and time goes by really fast. I think it is important to make sure to plan out the necessary steps needed to achieve your ultimate goal, regardless of what that end goal is.

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

I see myself continuing to perform research in evolutionary biology with a team of researchers. I am open to the possibility of leading my own independent research group, hopefully in an academic institution. At this point I know that I love performing research in the basic sciences and I am open to the possibility of doing research regardless of the type of institution that I end up performing it in.

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

I think CEHG plays an integral role in fostering interactions with many influential faculty members in the CEHG fields across Stanford campus. It also provides the opportunity to expand my network of potential collaborators by meeting other CEHG fellows that span a variety of different disciplines. Specifically, the Evolgenome seminar series is an ideal opportunity to present and engage with other members of the program through meaningful discussions with speakers and faculty members about their research.

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

My escape is music. I love seeing live shows, finding new artists and talking and sharing and experiencing music with friends. I tried to play music but I think I am much better at appreciating it!

I also like to hike and unplug from technology for a while, and I enjoy being in the moment, surrounded by nature. It’s a time for me to think and my mind resets in a way that I don’t get on a daily basis. I also enjoy snowboarding, running, and cooking.

Fellows Feature: Solomon Endlich

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Solomon Endlich is a CEHG postdoctoral fellow in the Gill Bejerano lab. He received his PhD in theoretical physics at Columbia University and has held postdoctoral positions at the École Polytechnique Fédérale de Lausanne and the Stanford Institute for Theoretical Physics. 

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

As a clear romantic, I am daily struck by the wonder of the natural world; I am overwhelmed with its majesty, its beauty, and its kaleidoscope of forms. These inspirational feelings have led me to focus my life on exploring it, intellectually and physically. From physics to biology, and from catching lizards in the backyard to performing technical scuba dives in the mighty Pacific, the narrative has pretty much stayed the same — there is always more to learn and always new things to explore.

This lifestyle has it drawbacks, of course. My garage looks like the used section of some kind of super outdoor shop; bags of ropes compete for space with drysuits and scuba tanks, while backcountry skis and outrageous winter camping gear try to stay relevant during the hot California summer months. Meanwhile, my strange (and large) book collection makes moving a huge pain. But what would I do without Lalli and Gilmer’s Pelagic Snails, or Munk and MacDonald’s The Rotation of the Earth – A Geophysical Discussion?

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

It is amazing working everyday at Stanford. I was born just across the Bay and always dreamed of being a scientist in a university. So everyday, walking into the lab feels like a dream come true.

I was born in Berkeley and raised in nearby beautiful Sonoma County. I was always romping around the forests or catching insects or reading books about sharks. To me, it was clear that I had to be a scientist, but it was not so clear what that actually meant or how one does that. My family are creatives (artists, designers) and I always felt a little bit like the black sheep. Lucky for me, I somehow found the right books to read and had the right teachers who encouraged me. I was directed to Jacques Cousteau, Richard Feynman, Carl Sagan, and Charles Darwin, and found my people.

Intellectually, I was always drawn to fundamental principles as opposed to collections of facts. I wanted to know the key features that united disparate phenomena. I was interested in *why* things worked the way they do. This led me down the rabbit hole of mathematical physics, where I then spent a solid portion of my adult life. Quantum Mechanics and General Relativity. Statistical Mechanics and Fluid Dynamics. Cosmology and Astrophysics. That rigorous quantitative experience gave me a new set of eyes that saw the world so differently then when I was a boy.

After my PhD and a few years as a postdoc, I felt like some of the excitement was gone. I wanted to be where discoveries did not happen on a decade-long time scale. I rekindled my love of the life sciences and found a calling in genomics. It had the fundamental nature (they are the instructions — the rules — that ultimately govern organisms) that I so enjoyed, but also a pace of discovery that I could only dream about. At the risk of being too bold, I knew immediately: “This is where the action is!”

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

My current research has shifted quite a bit since I began my fellowship. Frustrated with the quality of the various vertebrate genome assemblies, I became more and more interested in all the missing pieces (and there are many!). What is lurking in uncharted territory? Entranced, I pivoted towards an ambitious new goal: sequence the unsequencable and *fully* map out the most important genomes. I told myself: “Since I am giving this genomics thing a try, why not pick a really audacious goal?”

It turns out that to some people, it may be too audacious. In the initial stages, I discussed my intentions with some visiting senior researchers and they kindly suggested I lower my sights and work on something more practical and secure for my career. Needless to say, I didn’t listen and, in fact, felt even more motivated.

The plan involves a combination of molecular biology and computational techniques (which I will not get into the details here) that, *if* they work, could be absolutely transformative for the field. To this end, I have been toiling away in the lab for the last 8 months to optimize the protocols and demonstrate a solid proof of principle. So far, I have had very encouraging data! Computational results indicate that the idea in question will, as hoped, give us an advantage over standard sequencing experiments, and the lab work has demonstrated that the needed chemistry can operate as needed.

At this point, all that is needed is to put the pieces together and see how much of an improvement we can really make. Even a partial success will then allow us to see genomes in more detail then we have ever before.

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

There are so many. As I mentioned before, I received a lot of support from my early teachers. Looking back, it seems incredible that a few kind words said at the right time can have such a big impact. [Thank you Dr. Karen Frindell, Mr. G, and Mr. Lee. Don’t know where I would be without you.] Years later, my close colleagues in physics very much shaped my attitudes and intuition: Alberto Nicolis, Riccardo Penco, and Rachel Rosen. They are all incredible scientists and have been role models for years.

More currently, the environment at Stanford has let me explore far outside my initial lab space. In the early stages of this project, I found Dr. Ashby Morrison in Biology and she opened her door to me to work on some “crazy” ideas. Without her, I am not sure this project would ever have gotten off the ground. There is also a whole list of students and postdocs who have been of invaluable help; Stanford has such an incredible pool of talent and energy!

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

Institutions like CEHG are absolutely vital to science at Stanford. The most interesting things happening are usually at the intersection of disparate fields. Almost by definition, if something has not been discovered, there can be no “department” of it. And in the same vein, many of the groundbreaking experiments and analyses in a given field often require assistance from other fields for their execution. Take, for instance, the human genome project: it was clearly a biology project, but one that took an enormous amount of molecular biology, engineering, and computer science expertise to bring to fruition. And institutions like CEHG set just such a tone and encourage scientists to stretch their research programs beyond the comfortable boundaries of their own disciplines.

And for me personally, CEHG gave me the freedom to search out an interdisciplinary opportunity and to collaborate with scientists whose expertise could compliment my own. So far, it has worked incredibly well.

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

If all goes well, I see myself doing research daily. Working with a team of people whose different areas of expertise illuminate the complex and many faceted problems of modern biology. But I also see myself interacting extensively with the public and the larger scientific community. As scientists, we can’t simply expect people to see the value in our work and support us in kind. I see myself engaged in this discussion, as well as working to inspire and support the next generation of inquisitive minds.

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

  • Keep your education general. You can spend a lifetime learning all the things that *could* be useful at sometime or another. Instead, focus on the problem that you want to solve and you can learn the appropriate tools as you need them.
  • Talk to people. They often know a lot more then you and can point you in the right direction. A couple conversations with the right minds can save you months of work.
  • Work with people you like and get along with, scientifically and emotionally. We all take our work very personally (I know I do). Having colleagues that you are on the same wavelength with, and whose company you enjoy, will greatly improve the experience and ultimately make your work easier and better.

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

Too many hobbies actually. I may have to start making some hard choices! I participate in lots of outdoor activities, the more “adventure-y” the better: rock climbing (personal goal: climb “The Nose”); backcountry skiing (it is like winter hiking, but with a cherry on top); scuba diving (most recently, I have been trained to use a rebreather); fly fishing; and cycling. These go a long way toward scratching the adventure/explorer itch, especially when you share the experience with friends.

On the creative side, I have recently picked up ceramics, which has been a wonderful way to slow down an otherwise overactive mind. Very meditative, with the side benefit of being great for gift giving.

Fellows Feature: Gili Greenbaum

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Gili Greenbaum (giligreenbaum.wordpress.com) is a CEHG postdoctoral fellow in the lab of Noah Rosenberg. Gili completed his B.Sc. in mathematics and philosophy at the Hebrew University of Jerusalem and his M.Sc. and Ph.D (Physics and Ecology departments) at Ben-Gurion University, Israel. He is interested in population-level evolutionary dynamics and complex-systems theory, and is working to understand how complex spatial structuring impacts evolutionary processes. 

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

I grew up in the Galilee in Northern Israel. There, I spent a lot of my time turning over rocks to see what was under them and following ants to see where they were going. I was also very much interested in math. Eventually, I started my academic route at the Hebrew University of Jerusalem, where I studied both Mathematics and Philosophy. During my studies, I also worked for the Society for Protection of Nature in Israel, so as to remain connected to the natural world. I worked with nature-education and hiking activities for kids and teenagers. After finishing my B.Sc., I joined the Israel Trails Committee, where I was working on developing hiking trails, particularly new long-distance trails.

In order to bring together the various disciplines that interest me – mathematics, evolutionary biology, and conservation biology – I decided to focus on mathematical population genetics, joining the Physics and Ecology Departments at the Sede Boker campus of Ben-Gurion University on an inter-disciplinary fellowship. Although I worked mainly on theoretical and methodological problems, I kept grounded by collaborating on conservation projects.

How did you end up here? How did you first become interested in genetics and science?

Ever since I heard about it (don’t quite remember when that was), I thought evolution was the coolest idea ever. I still get dizzy when I think too deeply about it, biologically, mathematically or philosophically. For a long time, I wasn’t sure what would be my research focus, and I explored different topics (from math and physics all the way to philosophy and history), but when I had to settle on a field for my graduate studies, it was clear to me that I would study evolutionary theory. I always liked reading popular science books, with perhaps Richard Dawkins and Douglas Hofstadter having the most impact, and I believe that these early readings played a significant role in steering me towards a career in science.

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

During my Ph.D. I was lucky to observe and think about several different biological systems in different parts of the world, such as Asiatic wild ass, Przewalski’s horses, Nubian Ibex, collared lizards, bats, and even Acacia trees and other plant systems. These experiences have helped me appreciate the complexity of many natural systems, and be aware of the difficulties of understanding and modeling evolutionary processes in real-world systems.

My work is focused on developing approaches for inference and prediction of population genetics that incorporate the structural complexities, at the population level, that are more often the rule rather than the exception in natural systems. In my work, I try to draw ideas from complex systems theory, particularly network theory.

One of the projects that I have been working on is to develop a data-driven network-based methodology for inference of population structure that minimizes the a priori biological assumptions needed, that is applicable to whole-genome datasets and that can describe simultaneously many hierarchical levels of population structure. For example, analyzing a world-wide Arabidopsis thaliana, we were able to describe very fine-scale population structures, sometimes restricted to single rivers or adjacent to specific cities, but also retain the context of the coarser world-wide structure.

Besides inference of population structure, I am interested in the evolutionary consequences of structured populations when the structure is complex and does not conform to simple topologies, such as in the Island Model or the Stepping-Stone Model. For example, under a given complex population structure, I am interested in understanding which types of evolutionary processes are more likely to occur (e.g. global selection, local adaptation, erosion of genetic diversity, etc.). I am looking into connecting theory on generative network models to theory of population structure, by analyzing population genetic properties of such models under a coalescent-theory framework. This line of work can be particularly useful in the context of conservation, since our goal in conservation is not only to maintain endangered populations, but also to consider their evolutionary trajectories.

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

I have really been fortunate to be mentored by fantastic people. In my Ph.D. studies, I was mentored by Alan Templeton, a Professor at Washington University. We spent many days in the Ozarks, catching collared lizards and talking about (almost) all of science. These chats made me appreciate the fact that being a specialist in a scientific field and having a broad scientific interest are not necessarily in contradiction. Now, at Noah Rosenberg’s lab, I am again lucky to find myself mentored by a researcher who is both an expert and retains an immensely large scientific scope (check out our lab’s library!). I am hoping that some of the abilities of these great people–to be experts and, at the same time, be involved and interested in many topics–will rub a bit onto me.

What are the differences between the US and your home country (or the country of your previous study)? Have you enjoyed your time at Stanford so far?

Stanford is a fantastic place to do science. So much cutting-edge stuff is going on all around you. Hopefully, you’ll get infected by some of it.

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

Keep doing what you are most interested in. That’s as much as anyone can ask, I guess, and in academia, that is really your mission. Sometimes it seems complicated, and there are struggles, but in the end it actually is pretty simple.

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

CEHG is all about combining different perspectives to better understand evolution and genetics, an approach I truly believe in. The scientific community today is huge, and continuously expanding, and CEHG helps tie together different points in this expanding scientific space so we can make some sense of the bigger picture.

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

My goal is to start my own lab, and continue exploring and expanding evolutionary theory. In particular, I would like to address the current issues that are on the minds of conservationists, and develop ideas that can help us address some of the evolutionary consequences of the Anthropocene.

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 being outside, hiking long-distance trails. I hiked long trails in in Greenland and Iceland, across Europe, Central and Eastern Asia, and the Israel National Trail is, of course, a favorite. Haven’t gotten to the US long trails yet. Nowadays, with my two boys, I prefer less long and less harsh trails, but I am learning to enjoy other things on shorter hikes, such as the way spider webs stick to your fingers and how funny some acorns are.

 

Fellows Feature: Alison Feder

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Alison Feder is a CEHG graduate fellow in Dmitri Petrov’s lab. Before coming to Stanford, she received her BA in mathematics at the University of Pennsylvania and her MSc (res) in statistics at the University of Oxford. Her current research is focused on using the dynamics of HIV drug resistance evolution as a model for understanding how rapid adaptation proceeds across space and time.

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

I grew up in Chicago. I went to college at the University of Pennsylvania, where I earned a BA in math and developed an enthusiasm for quantitative evolutionary biology. After graduation, I pursued an MSc by research in statistics at Oxford before moving to Stanford for my PhD.

How did you end up here? Tell us a bit about how you first became interested in genetics and science. 

I took a world-expanding statistics course with Rosa McCullagh in high school and knew I wanted to do something that involved understanding data quantitatively. Someone told me (probably incorrectly) that one could do either econometrics or biostatistics. I liked high school biology much better than high school economics, so I figured I’d better just be a biostatistician.

When I arrived at college, I sought out a research experience combining biology and statistics. My initial inquiries led me to Warren Ewens, a Big Deal population geneticist, who I definitely would have been too intimidated to email had I understood how Big a Deal he was. Warren handed me a stack of population genetics books, suggested that I read what I wanted and then come back to talk about whatever I found interesting. I came back every week that semester. These conversations ultimately led to a small project investigating inference from nucleotide substitution models.

However, I did the bulk of my undergraduate research in Josh Plotkin’s lab, upon the recommendation of a then-stranger in a computer lab who saw me designing a course schedule featuring both math and biology.

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

I’m interested in how natural populations adapt when strong population genetic forces are at play. In my PhD, I’ve studied this adaptation in the context of HIV drug resistance evolution. In the late 1980s/early 1990s, we treated HIV with single drugs that led to fast and predictable acquisition of drug resistance. Now we treat patients with efficacious combinations of drugs that rarely lead to resistance. What makes these drugs work so well, and why do they sometimes still fail? In answering these questions, I think we can learn a lot about evolution in huge populations under strong natural selection.

One mystery that fascinates me is HIV’s ability to evolve when it’s treated with three drugs simultaneously. We think that this should be very difficult because HIV should need not just one or two but three different mutations to be able to replicate at all in the presence of three drugs. Further, we might expect that any single mutation shouldn’t help the virus, because it will still be suppressed by two other drugs. Yet somehow, drug resistance does sometimes still emerge, and the mutations that confer resistance to single drugs can spread within patients one at a time.

Our mental model of HIV intra-patient evolution is missing some important factor that accounts for this behavior. I’m trying to understand what this intra-patient evolutionary process looks like using a combination of clinical and experimental HIV sequences, genomic analysis and mathematical modeling. If we can resolve how HIV can win against three simultaneous drugs, maybe this can help us understand more generally how populations solve seemingly impossible evolutionary tasks.

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

So many people have been so important towards my scientific development:

Warren Ewens first introduced me to the field of population genetics, and spent an inordinate amount of time fielding absurdly naive questions with admirable enthusiasm.

Josh Plotkin welcomed me into his lab as a first-year undergrad even though I basically had no skills whatsoever. Despite this, he trusted me with a project and provided direct mentorship and unceasing support for years. He cultivated a lab environment and research program that made me want to go to graduate school and become a scientist. To this day, I can trace the bulk of my scientific interests to discussions in Josh’s lab as an undergraduate.

Pleuni Pennings has been a mentor, a colleague, a friend and an ever-flowing source of inspiration, both scientific and otherwise. Every time we talk, I walk away with three new projects ideas and renewed excitement for my scientific endeavors. Below I’m asked to give some advice. Here it is: find your Pleuni Pennings.

I don’t know how I got so lucky as to stumble into Dmitri Petrov’s lab. Dmitri is an incisive thinker, gifted communicator and fantastic mentor. I frequently feel like I come up with ideas only to realize that he had actually suggested something similar three weeks ago that I just hadn’t fully understood. He’s also just a kind and compassionate person, and one of the things that has made my graduate school experience so fantastic has been his commitment to maintaining a lab full of people who like each other.

I also want to highlight in particular the postdoctoral mentors I’ve worked with in the past who have taught me the vast majority of my practical skills: Kirk Lohmueller, Alan Bergland, Jeremy Draghi and Sergey Kryazhimskiy.

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

My best experiences in science have been in working with people I like. If you enjoy talking with someone, those conversations will naturally result in new ideas and directions. Science is hard, and being surrounded by a network of support makes a huge difference. Related to this, I think I’ve benefited tremendously from seeking out advice from lots of mentors. Everyone brings their own set of experiences to the table, and trying to see a problem from many perspectives has often kept me from getting too stuck.

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

Stanford is huge and dispersed. I am confident that there are fantastic scientists doing extremely relevant research here on campus that I’ve never even heard about, much less met. However, if it weren’t for CEHG, I am also confident that there would be many more. CEHG’s seminars, symposia and other events make the genomics community on campus accessible across departmental, school and university lines.

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

I’ve actually just defended my dissertation. Next year, I’m moving on to Berkeley to do a postdoc with Oskar Hallatschek and Monty Slatkin. I’m excited about trying to understand how populations solve difficult evolutionary problems by separating them into simpler problems in space and time.

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 play soccer and lots of board games. I also like messing around with drawing and animation when I have the time. Inspired by Pleuni Pennings, I’ve begun making animated video abstracts for my research that are hopefully accessible to a broad audience. Here’s one I made about how better HIV therapies have fundamentally changed the way that drug resistance evolves within people:

Fellows Feature: Boxiang Liu

Boxiang Liu 192_ForWeb

Boxiang Liu is a CEHG graduate fellow supervised by Dr. Stephen Montgomery and Dr. Thomas Quertermous. He graduated from Illinois Wesleyan University in 2013. His primary research objective is to finemap disease-associated causal variants in specialized cell types, with a focus on coronary artery disease. 

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

My name is Boxiang. I am co-advised by Stephen Montgomery and Thomas Quertermous. My research primarily focuses on explaining molecular mechanisms of genome-wide association risk variants – asking questions like, why do they influence disease risk? What proteins/pathways do they affect? How do they affect such proteins/pathways?

I enjoy collaborating with other scientists, as well as educating non-scientists about what we do in the laboratory.

How did you end up here? How did you first become interested in genetics and science?

I became interested in genetics by accident. I competed in math Olympia in high school and also became a math major during my freshmen year. Later in college, Professor Gabe Spalding and Professor Thushara Perera made me interested in physics. Gabe and I build an optical trap and a custom microscope from scratch; Thushara and I wrote a paper on special relativity. Both of these activities helped me think critically and solve problems creatively.

After coming to Stanford, my initial objective was to extend my undergraduate research and to use optical traps to study protein and RNA folding. After rotating in a few labs, I realized computational genetics piques my interest more than biophysics. As a result, I joined Stephen Montgomery’s lab, in which I learned the tools to analyze sequencing data. At the same time, Thomas and his lab provided me with valuable sequencing data, and taught me quite a bit about molecular genetics.

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

My research primarily focuses on finding molecular mechanisms to explain genetic variants that influence complex traits and diseases. I am going to wear my scientist’s hat and use some jargons to get the points across.

The recent decade saw an explosion of genome-wide association studies (GWAS). The cumulative number of associated risk variants has grown from 2 in 2005 to 41,775 in 2016, averaging a 2-fold increase every year. The majority of these variants (~90%) lie in non-coding regions of the human genome. Although not directly coding for protein sequence and structure, these variants are able to modulate the level of protein expression via regulatory mechanisms, such as interacting with transcription factors and histone binding proteins. Unlike variants in the coding region, we cannot directly infer the target protein of non-coding variants or the direction of regulation from genetic sequences alone. Because of this, the majority of GWAS variants have not been functionally linked to any gene or gene product. Further, the regulatory functions of non-coding variants are largely contextualized on tissue/cell types as well as the extracellular environment. We argue that a portion of the unexplained variants can be linked to their target genes in disease-relevant cell types and treatments. We demonstrate the use of specialized cell types for 1) age-related macular degeneration (AMD), and 2) coronary artery disease (CAD). Using expression quantitative trait loci (eQTL) as a link between genetic variants and gene expression, we identify several novel potential causal genes that can modulate the risk of AMD and CAD.

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

Stephen [Montgomery] and Tom [Quertermous] are great. Stephen is very good at logical thinking. He can pick out the logical inconsistencies from my presentation or manuscript very easily. Tom is very encouraging and kind. He always find a way to make me feel good about myself.

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

Learn math (esp. statistics) and computer science (esp. machine learning). Read lots of papers and books. Talk to lots of professors/fellow researchers. Take good notes about your analyses. Celebrate small successes.

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

I hope to find a faculty position.

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

CEHG plays a crucial role in bringing people together from all aspects of genetics. The speaker series and the annual symposium are both examples of that.

What are the differences between the US and your home country (or the country of your previous study)? Have you enjoyed your time at Stanford so far? 

The gap between China and the U.S. is closing very quickly. I would say the biggest difference is the amount of attention from advisors. In China, students generally receive more attention and are expected to produce papers from early on. Here, advisors are generally more relaxed and let students explore on their own.

Stanford is a fantastic place. I enjoy doing research here very much.

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 play badminton and basketball. I currently train/play 3-4 times every week on badminton. I read books. I try to read one book per week.

Fellows Feature: Sur Herrera Paredes

428A2066_ForWebSur Herrera Paredes is a CEHG post-doctoral fellow in the lab of Hunter Fraser. He is a graduate of the University of North Carolina at Chapel Hill. His research focuses on understanding the genetic basis and evolutionary consequences of host-microbe interactions.

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

I was born and grew up in Merida, Yucatan, Mexico. I went to college at the Cuernavaca campus of the National Autonomous University of Mexico (UNAM), where I enrolled in the Genomics program. That program was one of the first in the world that attempted to integrate computational and quantitative skill with the biological sciences, and it emphasized direct research experience. At the time, I worked on bacteriophage genome analysis and I got generally interested in what genomics can tell us about interactions between organisms.

After graduating college, I came to the US to work in a lab studying the root microbiome at the University of North Carolina at Chapel Hill, and I ended up staying there for my PhD in Bioinformatics & Computational Biology. During my PhD, I continued to work on plant-microbe interactions in the root and rhizosphere, trying to understand both the host genetic elements that control root colonization by bacteria and the effect that bacterial strains and/or consortia have on plant phenotypes.

From my work on plant-microbe interactions, I got interested in evolutionary questions regarding microbial adaptation to the host. It was that interest which drove me to the Fraser lab at Stanford, where I currently work.

How did you first become interested in genetics and science? Did you always want to be a scientist?

I always was attracted to research. There are many academics in my family, all of them work in social sciences and the humanities. I grew up reading and listening to mostly discussions about philosophy, political science and literature. I think that growing in that environment taught me how to approach and dissect complex problems where the unknowns greatly outnumber the certainties we may have. It also taught me to always question those certainties.

I probably would have been a social scientist, but, when I was twelve, I read Darwin’s autobiography, and when I was thirteen, I learned about Mendel’s experiments at school. I was fascinated by the fact that so many aspects of biology could be explained by so few and simple principles, but what really surprised me was that both scientists achieved their contribution through completely different approaches: Darwin through observation, and Mendel through experimentation.

I wanted to study genetics since then, and I was very lucky that UNAM created a genomics undergraduate program as I was starting high school. I really didn’t understand the difference between genetics and genomics at the time; I probably just thought they sounded similar, but as it turned out, it was one of the best decisions I have made since the UNAM’s program put me in direct contact with the bleeding edge of modern biological research, which led me to pursue a PhD and ultimately to my current work at Stanford.

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

In general, I am interested in biological mechanisms that link processes happening at multiple scales. As such, I find that inter-kingdom interactions are a unique opportunity to integrate the study of molecular processes with their implications for ecological and evolutionary scales. At the Fraser lab, I focus on characterizing the evolutionary processes that govern host-microbe interactions and microbe-microbe interactions within a host, and the role of these interactions on host health.

For one project, we are focusing on the role of microbial genetic variation within the human host. While the abundance of bacterial species and genes has been extensively studied in the human host, little is known about the evolutionary forces that shape bacterial genomes within hosts. I am leveraging bacterial genetic variation, inferred from metagenomic sequence data, in order to identify bacterial genes and pathways that are under positive selection in the human host. Furthermore, we want to know how bacterial genetic variants influence host health.

Besides bacteria, the human microbiome also includes microbes from other kingdoms (archaea and fungi). Specifically, bacteria-fungi interactions are relevant in the context of opportunistic infections, but almost nothing is known regarding bacteria-fungi communication and interaction among commensals in the human microbiota. Using yeast as a model, and a method developed at the Fraser lab that allows for high-throughput massive-parallel precision genome editing, I am investigating how yeast genetic variants associated with the human host influence the interaction of yeast with the bacterial human microbiota. Our goal is to identify novel genetic components of the molecular communication between yeast and bacteria, and to characterize the evolutionary forces that shape the evolution of those interactions.

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

Many people have have been essential for my professional success. It would be impossible to name them all, but I think that my family and their support has been essential. Also, all my lab mates, co-authors and collaborators have enriched my academic performance. And finally, my mentors over the years: Guillermo Dávila Ramos, my undergraduate mentor who let me work on a project I proposed, and that he knew nothing about; Jeff Dangl and Corbin Jones, my PhD co-advisors, who continuously pushed me to do the best science possible; and Hunter Fraser, my post-doctoral mentor for the last year, who has supported me in what is a novel direction for his lab.

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

I think that the most important things are that you enjoy what you do, and that you find people that you enjoy working with. There are many possible paths to achieving whatever goals, so one has to be open minded and work hard to achieve those goals, and working hard is much easier if you are having a good time.

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

I am influenced by my family of academics, but I see myself staying in academia and performing basic research for a long time. I would like to lead my own independent research group in a university setting that gives me the opportunity to participate in the training of the next generation of scientists. I would like to be in a place where there is high potential for many cross-disciplinary interactions, and with a strong commitment to basic research and cultural diversity.

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

I think CEHG is a fantastic organization for Stanford. One of the challenges at a big university is how to ensure that there is a forum to create synergistic interactions between different research groups. I think CEHG fulfills that role and it further helps to foster interaction between junior and senior researchers.

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

My hobbies have changed over the years. Since I did my PhD in a “plant lab,” I have been trying to learn how to germinate different types of plants. I enjoy literature; recently I have been focusing on Latin American literature, and English classics. I also like reading philosophy. I also enjoy biking and am learning how to fix my bike myself. I used to play a lot of chess when I was a kid; I left it for years but, thanks to two lab mates, I’m picking it up again.