Fellows Feature: Yuping Li

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Yuping Li is a graduate student in the Department of Biology at Stanford. She is co-advised by Professors Gavin Sherlock and Dmitri Petrov. Her Ph.D. work has been focusing on combining a DNA-barcode lineage tracking system in S. cerevisiae and experimental evolution to understand short-term adaptation and trade-offs.

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

This is Yuping. I am a graduate student in the Department of Biology, jointly advised by Professors Gavin Sherlock and Dmitri Petrov.

I grew up in a small village in northern China, where the concept of research was foreign to most people. My interest in science started to build up through science classes in middle school. I had a special interest in physics at that time. During high school, I learned about DNA in biology classes for the first time and became fascinated about how almost all biological systems, ranging from microbes to plants and animals, were encoded by the same fundamental DNA blocks. Aiming to learn more about genomics and possibly how to crack the DNA code, I decided to major in bioinformatics in college. While I greatly enjoyed analyzing sequencing data and inferring biological insights out of it, I found myself lacking the basic skills to understand how most biological experiments were conducted. Thus, I worked as a technician in a genetics lab after college, where I finally got my hands wet.

Fortunately, I was able to pursue my interest in biology through graduate school. During my graduate school research, I combined high-throughput sequencing and experimental evolution to study evolutionary processes, which enabled me to practice and further improve my skills in both computational and experimental biology.

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

I wanted to become a scientist since I was child. However, it was unclear to me what scientists really do. My impression of scientists was mainly from cartoons, where they experimented with different colors of liquids and got something cool out of them (like the magic potion that makes people shrink to the size of ants). Thinking back I am actually not sure whether I was more attracted to the idea of being able to do specific experiments or the cool things those cartoon scientists always ended up with.

I first got seriously interested in genetics in high school. It was the early years of the human genome project. I remember that I was very excited and shocked by the idea that we could crack the secrets of humans by sequencing genomes, which eventually led to my decision to major in bioinformatics in college.

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

Evolution is the driving force of the biodiversity we are seeing on our planet today. However, our knowledge of evolution is still very limited. This limitation is largely caused by the fact that we cannot go back in time and dissect the evolutionary process step-by-step. Fortunately, microbial experimental evolution–evolving fast growing microbes under well-controlled laboratory conditions–provides the opportunity to study evolutionary processes in real time. In my current research, I evolve yeast populations in seasonal conditions and characterize different performances that are changed in order to adapt to these conditions. Moreover, by genome-wide sequencing adaptive clones, I study the genetic basis of adaption specific to each evolutionary condition.

One question I am interested in is whether and how evolution is constrained. Trade-offs have been widely assumed in the study of evolutionary and function biology; for instance, organisms adapted to cold conditions (e.g. polar bears) trade-off in hot conditions and vice versa. However, the prevalence of tradeoff and its underlying mechanisms is poorly understood. In my current research, by evolving yeast populations in one condition and measuring their performance in another, I am able to explore this question.

While evolutionary studies may sound very basic and inapplicable to our day-to-day life, I want to point out that they are actually very important in many real-world problems. For instance, human health-related problems like antibiotic resistance or cancer progression are evolutionary processes, where either pathogenic bacteria evolve to tolerate antibiotics or normal human cells happen to pick up mutations that enable them to propagate uncontrollably. Understanding these evolutionary processes will greatly contribute to our ability to design more effective treatments for these problems.

My graduate school work has been focusing on how evolution works in a population with a single species. In the next step, I am interested in continuing the study of evolution in a multi-species system and hope to characterize how species interaction contributes to the evolutionary process.

Briefly, what’s the coolest thing about your work?

Most of it would have sounded like a science fiction to me if I didn’t study biology. We are able to observe evolution in real time and, more importantly, pinpoint what mutations caused it. This to me is incredible.

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

There are a lot of people who have helped me along the way to becoming a biologist. It would have been impossible for me to get where I am today without their help.

First, I want to thank: my high school biology teacher, who introduced me to the genomics world and was a great inspiration for me to pursue a major in biology; my college mentor who taught me a lot about bioinformatics; and my mentors in the lab I worked in as a technician, who taught me how to do lab work (for instance, running PCRs and western blots).

Second, I want to thank my current advisors, Gavin and Dmitri, who have been actively involved in every part of my training in graduate school, and who have been extremely supportive. They have guided me on the way to learning how to form scientific questions, diagnose problems, write papers and eventually become an independent researcher.

Last, I want to thank my lab mates and collaborators. I have gotten so much help from them (literally) every day in the lab. I want to thank them for both their scientific and emotional support.

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

First, seek advice from people around you, your fellow graduate students, lab mates, advisor, other faculty members you get a chance to have a conversation with, and so on. We are surrounded by brilliant people with different areas of expertise. They are great resources to ask for research feedback, to brainstorm new ideas, and even to form collaborations. I have been amazed by how generous people are about their time and how much I have learned from my conversations with them. So, don’t hesitate to ask for advice!

Second, go to conferences if you can. Personally, I find conferences the best opportunity to connect with the scientific community and to keep updated with the research in my subfield. Moreover, I got lost in my lab work sometimes, without thinking about the big picture. Going to conferences helps me refocus and re-analyze my own project critically.

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

In the short term, I am graduating this summer and going to join the Bondy-Demony lab at UCSF as a postdoc soon. I am very much looking forward to it.

I am hoping to become a professor in the later stage of my life. I enjoy doing science, and hope to get the opportunity to mentor the next-generation of scientists as well.

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

CEHG has played an essential role in bringing evolutionary biologists, population geneticists, human geneticists, and ecologists on Stanford campus together. It has facilitated interdisciplinary communications and collaborations among us. I have greatly enjoyed the annual CEHG symposium and EvolGenome seminars. I feel honored to be involved in the CEHG community with whom I share my research interests and am able to seek for different perspectives. Furthermore, my graduate school work has been a combination of experimental biology and quantitative biology, which would have not been possible without the collaboration with theoreticians in the CEHG community.

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 working out, for instance, hiking, jogging, playing ping-pong, and rock climbing in my spare time. It helps me a lot to clear up my mind and refresh myself. I also love traveling, especially to places with great nature. It is always exciting for me to see unique landscapes and different plants/animals.

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Fellows Feature: Katya Mack

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Images courtesy of Katya Mack.

Katya’s work focuses on regulatory evolution on multiple times depths. She uses large-scale genomic datasets to uncover Darwin’s “mystery of mysteries”: how species are formed and maintained, as well as how populations adapt to new environments. She is currently a postdoctoral fellow in Hunter Fraser’s lab at Stanford University.

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

I grew up near Chicago, IL. When I was a child, I never envisioned growing up to be a scientist. I come from a family of really curious people who are fascinated by the natural world, but none of whom pursued science professionally. I remember spending a lot of my childhood being outside – hiking, backpacking, hunting for newts. I think this time led to an early appreciation for biological diversity.

After graduating high school, I attended University of Michigan, where I earned a BS in Anthropology. It was in college, after working in a research lab, that I first realized that a career in science was an option for me. I then pursued a PhD at the University of California, Berkeley, where I worked with Michael Nachman in the Museum of Vertebrate Zoology. There, I studied gene regulation and the genomic basis of speciation and adaptation in house mice. Now, I am a postdoctoral fellow in Hunter Fraser’s lab here at Stanford.

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

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I really started to become interested in genetics in college. After starting college as a visual arts major, I began taking classes in the Anthropology department because I was fascinated by human evolution. It was at this time when the first Neanderthal genome was published, and I remember being absolutely amazed by what we could understand about an extinct group and human evolution from genetics alone. It was this fascination that led to me working as a research assistant as an undergraduate and eventually pursuing a PhD. Now, I see studying genetics as a way to understand the amazing diversity of lifeforms we see on earth, including humans. I think it is really fascinating to understand the common processes that allow species to adapt to life on earth.

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

My research is focused on understanding the role of gene regulation in evolutionary processes. Gene regulation is the process of controlling how genes are expressed (e.g., turned on or off). In the past, there has been more of an emphasis on understanding changes in the genes themselves, rather than changes to gene expression. However, there is now evidence that a lot of evolutionary change happens on the level of gene regulation.

A good reference point I always come back to is that human and chimpanzees are actually very similar on the protein level. The similarity of humans and chimpanzees on the protein level means that many of the amazing anatomical and behavioral differences between humans and our closest living relatives are not due to changes in proteins themselves, but how they are modulated.

To understand the role of gene regulation in evolutionary processes, I’ve been working with a variety of systems to characterize gene expression differences within and between species and associating these differences with phenotypes. For example, a project that I worked on during my PhD looked at how genetic variants associated with changes in gene expression contributed to body size variation in mice. Mice in the eastern United States vary in size based on a temperature gradient. Mice in New York are larger and fatter to reduce heat loss and contend with colder temperatures, while mice in Florida are smaller and lighter. We found that changes in gene regulation contributed to a large component of the variation in body mass in these mice – and interestingly, the genes we identified were ones that had also been associated with body weight variation in humans.

The results of this research can help provide a framework for understanding the role of gene regulation in phenotypic evolution. The long-term next steps will be to incorporate what we are learning from gene expression evolution in different systems to characterize general patterns and build accurate predictive models.

Briefly, what’s the coolest thing about your work?

I think the coolest thing about my work is being able to look at the diversity we see in nature, chipping away at the “how” of it, and identifying generalities that cross different realms of life on earth.

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

I’ve been really fortunate to be mentored by fantastic people and also receive a lot of support from friends and family. One of my earliest research experiences was as an undergraduate research assistant in Dr. Patricia Wittkopp’s lab at the University of Michigan. At the time I didn’t have any idea what a career in science even looked like. I was fortunate that this formative experience in a lab was really positive: I was working with smart, but patient, people on a project that I found really interesting and challenging.

I remember at one point, the postdoc whose project I was working on handed me an “introduction to programming” book and basically said, you know our question, here’s the data, figure out how to answer it. I had room to learn on my own, but if I got stuck, I also had someone to check in with. When I work with undergraduates now, I always look to that experience as a model for how to successfully mentor students.

In the time since then, I have been really fortunate to be mentored by many other fantastic people like my PhD advisor at UC Berkeley, Michael Nachman, other faculty and colleagues at UC Berkeley and other institutions, and now Hunter Fraser here at Stanford.

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

I hope to continue pursuing a career in science, either as a university professor or in industry. My hope is that I will be able to continue addressing interesting questions with big genomics datasets!

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

My first piece of advice is to seek out good mentors. I think a big component of how much I’ve enjoyed my time in science thus far comes down to the supportive mentors I’ve had. A good mentor for you can be very different than a good mentor for someone else, so I believe figuring out what you want/need from a mentor and communicating those needs is essential for a positive mentor-mentee relationship.

Second, I think it’s important to say “yes” to opportunities when they arise. While you want to spend the majority of your time pursuing the work you are ultimately the most passionate about, taking on other opportunities – like interesting side projects, teaching a short course, or volunteering in your department and community — can be really valuable. I see this strategy as serving two purposes: 1) when one or more things fail – which they will – you always have something you are making progress on, and 2) you’ll continue stretching yourself and gain a more diverse skill set in the long run.

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

CEHG is incredibly valuable because it brings together scientists of different disciplines who are using genomic and genetics tools and datasets, fostering interdisciplinary and collaborative research. It provides researchers in the Stanford community an opportunity to expand their network of potential collaborators through participation in the center’s activities. Biological research is increasingly dependent on interdisciplinary efforts, and interdisciplinary approaches have really benefited my research. I see CEHG’s efforts to foster this collaborative environment as really valuable for the Stanford community.

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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 have more hobbies than I can reasonably keep up with. I love camping, hiking, and just enjoying the outdoors. On the more creative end of the spectrum, I enjoy painting, crafting, and have recently taken up embroidery. I also always find time to read; I particularly enjoy science fiction and nonfiction adventure books.

 

Fellows Feature: Laura Bogar

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Laura Bogar is a Ph.D. Student in Stanford’s Department of Biology and the Peay Lab. Her PhD work is focused on symbiotic interactions between land plants and soil fungi. She earned her undergraduate degree in Biology at Lewis & Clark College in May 2012. 

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

I was born in Seattle, Washington, and grew up loving the mountains and forests of the coastal Pacific Northwest. Both of my parents love the outdoors, and we spent a lot of time as a family exploring local parks and doing more ambitious multi-day backpacking trips when my brother and I were old enough. I attended public schools in Seattle through high school, where I spent most of my time directing plays with the drama club, singing in the vocal jazz ensemble, and removing invasive ivy from local parks.

After graduation, I attended Lewis & Clark College in Portland, Oregon, to get my bachelor’s degree in biology while dabbling in the liberal arts. As an undergraduate, my extracurricular focus shifted from performing arts to environmental activism: I advocated for renewable energy, worked as a resident advisor for the sustainability-themed floor, and led environmental education trips focused on plant and mushroom identification. In choosing my major, I was mostly guided by a vague sense that I might like to work outdoors.

Luckily for me, a couple of my biology professors suggested that I get involved with science research, and by the end of my undergraduate career, I was hooked on plant-fungal symbiosis. After I graduated, I spent a few months working with my mentors on ecology research projects, then spent some time back in Seattle recruiting underserved students for environmental conservation jobs. A year after graduating, I started my work here at Stanford with Kabir Peay.

Now, on the cusp of graduation, I have perfected the art of carefully growing tree seedlings, only to kill them inventively in standardized harvest protocols. (I also have done a lot of molecular and physiological work, although now I mostly code and write.) I love thinking and writing about the research, and teaching students about science and life in the lab.

 

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Experimental seedlings in the special chamber Laura uses for stable isotope enrichment. Image courtesy of Laura Bogar.

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

When I was a child, I wanted to write stories. I was a stubborn kid, motivated by an affection for words and by the alluring idea that I could build new worlds to share with other people. I wanted creative control and the chance to spend my time exploring mental landscapes that hadn’t existed before. At the time, I had no idea that a scientific career was a way to make this happen. I feel lucky to have landed in biology.

I was initially drawn to the field because I loved the language of it. Growing up hiking around the Pacific Northwest, I discovered that the more I could describe about natural history, the more I could see to be interested in. Rather than a forest of pines, I could walk through patches of Douglass fir, western redcedar, and western hemlock, noting with surprise the occasional grand fir outside its usual range. Instead of seeing lichens, I was delighted to find lettuce lung, frog’s pelt, or fairy barf, each in its own habitat. Ecological details provided the grammar of this new language, relating each new word to the others in gratifying and unexpected ways. Knowing which plants preferred moist soil, I could infer the hydrology of an area even on a bone-dry summer day. I felt as if the landscape could speak.

As I have continued my education as a biologist, my vocabulary has deepened and become more Latinate, and my grasp of ecological grammar has improved. The symbiotic interactions between land plants and soil fungi, on which my thesis is focused, is a dialect of natural history that still awaits a thorough translation into scientific English. (I hope my work contributes to this end.) The Rosetta stone for these interactions is likely written in nucleic acids, billions of copies quietly produced each day in every gram of forest soil. As sequencing technology improves, I like to think decoding this symbiotic language is only a matter of time.

I am a scientist because I think the natural world is beautiful – especially the weirder, slimier parts of it – and science provides the language I need to engage with it more deeply. Rather than building imaginary worlds to explore the human experience, as I hoped to do as a child, I get to guide my readers into new corners of the natural world, using science as a lens to reveal the astonishing details that make our lives possible. Genomics have opened up new dimensions of the natural world, and I am honored to be working at a time when the pace of discovery is so exhilarating. I am delighted to be in a field with all the creative control and sense of discovery that I wanted as a child, even if my career looks different than I expected.

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

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Ectomycorrhizal pine roots with symbiotic fungi (Thelephora terrestris). Photo courtesy of Laura Bogar.

I am interested in how plant roots and soil fungi work together in a mutualism called mycorrhizal symbiosis. Nearly all land plants rely on symbiotic fungi to help them acquire water and nutrients. I’m specifically interested in the ectomycorrhizal symbiosis, which links many big temperate trees (pines, oaks) with a diverse set of fungi, including some familiar edibles like chanterelles and porcini. My goal is to learn what makes this symbiosis tick, how these mechanisms have evolved, and how this affects the ecology of plants, fungi, and the forests they inhabit. I use genomics as a tool to understand both the mechanisms and the evolution of these (mostly) cooperative interactions.

In particular, I’m interested in how plants and fungi determine whether or not they are compatible with each other, and how they negotiate their cooperation. The symbioses that I study work kind of like a marketplace: plants feed carbon compounds to the fungi on their roots, and, in exchange, the fungi bring soil resources like nitrogen, phosphorus, and water back to the roots. A single plant may have dozens of fungi on its root system at the same time, and a single fungus can associate with several plants at once. Although these intimate, negotiated relationships are complex enough that we might expect them to be difficult to form, different groups of fungi have evolved this lifestyle dozens of times independently over the last hundred million years.

There are a lot of outstanding questions about how this works. Can a plant tell if one fungus offers it a better deal than another fungus? And, if it can tell, can it respond by giving the better fungus more carbon? How might the plant and the fungus communicate with each other throughout this process? And how has this intimate, complex relationship evolved so many times?

Knowing how this symbiosis works in these different fungi will help us understand how cooperation can evolve, in general, and how symbiosis can be maintained over evolutionary time. In addition, understanding how plants and fungi negotiate their trading interactions will clarify fundamental concepts in community and ecosystem ecology. Why do plants grow in some places and not others? (The fungi may have something to do with it.) How are fungal distributions related to plant distributions? On a larger scale, how does symbiotic trading affect carbon and nitrogen cycling through forests?

In my dissertation, I have used stable isotope labeling to try to understand how environmental context shifts the negotiations in this symbiotic nutrient economy, and have sequenced fungal RNA to explore how a fungus can engage in symbiosis with many different kinds of plants. In my postdoc, I plan to examine the extent to which plants might maintain diverse fungi on their roots as a way to hedge their bets against variation in the environment. I also hope to expand my work on the genetic tools that can allow a fungus to associate with many different plants, exploring how the genes that make certain fungi compatible with particular plants have evolved across related fungi.

Briefly, what’s the coolest thing about your work?

Most people don’t know that nearly all plants cooperate with fungi in the soil. I think the coolest thing about my work is that I’m learning some basic things about a symbiosis that is responsible for making the world a green place to live. Plants and fungi can trade, make “decisions,” and optimize their performance in ways that are philosophically similar to what we animals do. I like helping people think about the world from the plant and fungal point of view. 

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

I haven’t always been the best-directed future scientist. By the time I got to college, I had a vague sense that I might want to be a park ranger, or maybe a high school teacher. I figured I’d work something out while I was there.

I wouldn’t be here if it weren’t for the intervention of a series of supportive mentors and educators.

When I started college, I had no idea that lab research was something that an undergraduate might explore. My undergraduate mentors – Greta Binford, Paulette Bierzychudek, and Peter Kennedy – changed that, showing me that scientific research could be something I did well and enjoyed. Peter, in particular, launched me towards the PhD I am doing now by introducing me to mycorrhizal research with kindness, thoroughness, and a sense of humor, and he remains one of my most valued colleagues.

At Stanford, I have been working with Kabir Peay, who has been central to my intellectual development during my dissertation. Kabir does rigorous science with the groundedness of a California surfer, helping his students dream big and then follow up with well-designed experiments. He has encouraged me to be enormously independent in my research, which has been a real gift, and has left me with a dissertation that feels like the beginning of my very own research program. Kabir is consistently supportive and eager to direct me to resources that might help with my work. I am grateful for his mentoring and glad to be a part of his lab.

I would never have thought to envision a life in science without my early mentors, and could never have realized it without the ones who have helped me here. There isn’t room, in this blog post, to acknowledge everyone to whom I owe serious mentoring debt, but certainly my committee (Tad Fukami, Peter Vitousek, Mary Beth Mudgett), my Carnegie collaborators (Ted Raab, Ari Kornfeld, Jen Johnson), Don Hermann at Berkeley, and many other folks have all been essential parts of my career so far. My sincerest thanks to all of you.

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

I have had a good time in science so far because of several incredible strokes of luck and a lot of really excellent mentoring. This leaves me feeling unqualified to give much advice, but, in my experience, seeking good mentors is a good place to start.

Working on something that interests you, of course, helps a lot. It’s also important to make sure that, whatever your job, you spend a lot of your time actually doing the activities that you enjoy. This could be coding, writing, teaching, field work, molecular biology, or something else! What I enjoy about my work is that I get to do a little of all of these things.

Most of all, go easy on yourself, and keep trying even when everything seems to be going wrong. Being successful is mostly about enduring failure until something eventually works. Celebrating little successes, and focusing on the joys of the scientific process itself, can make the whole thing a lot more fun.

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

I plan to pursue a career as a university professor, ideally in a place with a view of the mountains. I’d like to have my own lab, devoted to figuring out the mechanisms that drive the ecology and evolution of plant-fungal symbiosis, and to be able to teach students about plants, fungi, mutualism, and ecology. I’m not sure yet if this will be at a research-intensive university, or at an institution that puts a greater emphasis on teaching alongside faculty research, but I know I will enjoy continuing to work and write and teach about these topics for many years to come.

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

I value CEHG’s ability to bring together researchers that are using similar genomic tools to answer all kinds of different questions. Through the CEHG community, I have been able to learn about genomic techniques that I might not otherwise think to apply to my own work. As a scientist who mostly works on plant-fungal symbiosis, it would be easy for me to miss out on the cutting-edge analyses that the human geneticists and the theoretical evolutionary biologists are developing. Being part of this community is a valuable way for me to gain perspective and ideas for my own work. It has also been concretely helpful as I work through my own analyses: colleagues that I have met through CEHG have coached me through analyses, steered me away from errors, and helped me interpret difficult data sets. I am grateful for the scientific support that the CEHG community provides.

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

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Laura backpacking in February 2019. Photo courtesy of Laura Bogar.

When I’m not working on science, I usually like to be doing something active with my friends. My lab mates have tolerated the accumulation of a well-stocked “sports grotto” under my desk, where my running shoes, climbing gear, swimsuit, and even some underused boxing gloves are ready for any athletic opportunity that might come my way. Mostly, I run. (I think I’ve probably done the loop around the Stanford Dish at least 400 times since starting here.) But I also love to hike, and sometimes climb, and play around with group fitness classes. On weekends, I can hardly resist opportunities to organize group events, from mushroom foraging expeditions at Point Reyes to chamber music concerts in the living room of my co-op household.

I also spend time outside of the lab doing science-related activities that aren’t exactly research. Some weekends you can find me with my lab mates, leading workshops about mushrooms for middle school students; other times, I might be preparing a talk for a local mycological society. I find myself working in between biological disciplines a lot, and have sometimes found it hard to keep up with everything that’s happening at Stanford (molecular biology, ecology, and physiology all contribute important techniques and ideas to my work). To address this, I helped establish the Biology Department’s annual “Surf ‘n’ Turf Symposium” a few years ago, an event that aims to bridge traditional divisions in biology, both on the basis of systems (terrestrial vs. marine) and scales (molecular biology vs. ecology). This event has dovetailed nicely with the interdisciplinary support that CEHG provides, and has helped me feel like a part of a cohesive biological community at Stanford. In general, I think that my scientific life is most rewarding when it involves elements of research, outreach, and collaboration, and I’m glad to be able to do all of this here.

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The group photo from the very first Surf ‘n’ Turf Symposium, in 2016. Photo courtesy of Laura Bogar.

 

 

Fellows Feature: Fiona Tamburini

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Fiona is a computational biologist focused on the relationship of the microbiome to human health. She received her BS in Biochemistry from Boston College in 2014 and is currently a fifth-year PhD student in Ami Bhatt’s lab.

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

I grew up in Connecticut and attended Boston College, so New England has a special place in my heart. Here at Stanford, I’m a fifth-year PhD student in Ami Bhatt’s lab in the Genetics department. I’m interested in the relationship of the gut microbiome to both infectious disease and noncommunicable disease, and most of my work focuses on computational analysis of microbial genomes and gut microbiome sequence data.

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

I was aware of the concept of genetics as far back as I can remember because I have always looked a lot like my mom, and it’s something people have invoked my whole life (“You look just like your mother, wow genetics!”). So that was always on my radar. And my father is a biochemist by training and worked in drug discovery for years and really hyped that career choice, which I, as an impressionable young kid, totally bought into. I was utterly brainwashed honestly, and I was devoted to the idea of becoming a scientist from a young age, but, interestingly enough, my mom (not a scientist but a smart lady) was the one who actually suggested that I explore genetics. She follows the lay science press closely and I remember talking to her on the phone during my first year of college, and she said something to the effect of “You know, I really think you’d like this genetics thing.” I joined a genetics research lab at Boston College shortly thereafter.

As a child growing up in the era of the Human Genomic project, I had always envisioned working in human genomics. I only developed an intense interest in bacteria and the microbiome after I had already arrived at Stanford. My advisor, Ami Bhatt, started her lab the same year I began graduate school, and I heard her give a talk at our department retreat, which utterly blew me away. Right around this time, I was also reading a book that my uncle gave me and there was a chapter on microbes that was so compelling, there’s one quote that I love — “Bacteria may not build cities or have interesting social lives, but they will be here when the Sun explodes. This is their planet, and we are on it only because they allow us to be.” And you know, after studying the gut microbial community for a few years, I think bacteria might have more interesting social lives than we give them credit for. 🙂

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

A major goal of our lab is leveraging the microbiome to improve the health of patients. In particular, we study individuals who have undergone hematopoietic cell transplant as a treatment for hematological malignancy. As you might imagine, these patients are immunocompromised and therefore very susceptible to infection – and we frequently don’t know where infectious organisms are coming from. We sought to identify whether organisms causing bloodstream infection may have originated from the gut, and found some interesting cases of infectious organisms thought to arise from the skin or environment actually colonizing the gut.

I think this work is important because it challenges the clinical dogma that infections microbes originate from a stereotypical source. The next step is to perform a larger prospective study to try to assess the relative frequency of BSIs from the gut. For a given organism, how often do we expect this to happen? And if this could be replicated at other centers that would be informative. And then we can think about how we might intervene – whether we can better manage gut health to prevent gut-derived infections, for instance.

The project that I’m spending most of my time on right now focuses on describing the gut microbiome composition of individuals living in two populations in South Africa, in collaboration with researchers from the University of the Witwatersrand in Johannesburg.

We are seeing increasingly that the microbiome is intertwined with – and may even drive – disease, yet we are largely in the dark as to whether the results of research studies carried out in the west are generalizable to other populations. What we’re seeing is that our methods and reference databases are incomplete for non-western individuals. These study participants have sequences in their gut microbiome that originate from genomes we haven’t described and are therefore not present in our reference collections. We are working to leverage recent improvements in metagenome assembly to better describe the gut microbiomes of these individuals.

Briefly, what’s the coolest thing about your work?

There are multiple reasons why studying the microbiome is cool — one big thing is that it’s a “hot” area of research right now and talked about a lot in the lay press. So it’s a subject that’s on peoples’ radar and that people are really interested in talking about. It’s generally easy to talk to non-scientists about my research and get them excited about the microbiome.

Another thing I love about my work is that it’s so immediately relatable to one’s daily habits. There’s a powerful relationship between diet and exposures and the microbiome – the average person can probably recall a time when they ate something out of the ordinary and felt differently! Of course, I can’t give medical advice, but it’s neat to be able to talk to people about how various sources of fiber can change their microbiome. That said, I’ve changed my habits surprisingly little given what I know about the microbiome. Knowing what I know, I should probably eat more cruciferous vegetables and fewer Reese’s’ peanut butter cups on a daily basis but here we are!

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

I certainly owe any success I’ve had to all of the advisors and mentors that I’ve worked with so far. I’ve been fortunate to have a series of nurturing mentors throughout my training – at Boston College, at a summer internship at UCONN Health Center, and here at Stanford. In particular my current advisor, Ami Bhatt, has pushed me to grow in my ability to posit a hypothesis and interpret results, but also equally importantly, she has encouraged me to conduct myself with confidence as a strong female leader in bioscience.

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

My advice is generally to follow your passion and your interests, but also find a supportive advisor whose mentorship style is compatible with your interests and goals. If you have an open mind and an inquisitive attitude, one can cultivate an interest in nearly any subject.

I would also emphasize the importance of grit and willingness to figure things out on your own. Coursework can be important to build foundational knowledge, but almost all of the skills that I employ on a daily basis in my work are self-taught and empirical. I think that there’s this myth that you need to take a bunch of classes to learn how to program or do computational biology, for instance, but I haven’t found that to be necessary personally. I think it’s better to have a research question and some data and hack it together and learn by doing and by asking questions!

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

I think that I’m driven mostly by interesting research questions, so I’ll see where the exciting opportunities are as I embark on the next step of my career, and go from there. Ideally, I’d like to work toward improving infectious outcomes for patients. A major unmet need is the ability to identify a pathogen and its antimicrobial susceptibility in real time so that doctors can utilize that information to make decisions about patient care including central line maintenance and antibiotic selection, and innovations in DNA sequencing hold great promise in that area.

CEHG’s core values include “interdisciplinary research” and “collaboration.” Can you speak to the ways your work has embodied these values or to their importance to your future work or past experience? 

Studying the microbiome in a clinical context requires expertise from many areas – including but not limited to genomics, microbiology, biochemistry, and medicine. I’m fortunate enough that our lab is incredibly interdisciplinary and I have worked closely with colleagues on every project I’ve been a part of at Stanford. That includes working with a clinical fellow in my lab on clinical trial data, collaborating with the clinical microbiology labs at Stanford Hospital, and working with researchers in the Microbiology and Immunology department.

In an ideal collaboration, each party comes away with a bit of an enhanced knowledge of the other’s domain, and I have been fortunate to learn so much from collaborations here at Stanford. I have also had the incredible opportunity to collaborate with researchers at the University of the Witwatersrand, from whom I have learned so much about how to handle a collaboration across great distance (and time zones!), as well as how to conduct human subjects research in an equitable and respectful manner.

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 got more involved in distance running in graduate school (I’ve run two marathons and am training for a third, yikes!) – there’s definitely a parallel there to the PhD experience in the sense that both are a long grind. I’ve also gotten into mountain biking lately. I’m not a super hardcore biker but I love that it allows me to cover more ground than I would be able to on foot. I also fall off my bike a lot — I’d like to think that builds resilience. Lest I fool anyone into believing I’m athletic, I am also very much into knitting and crochet. I always have one too many yarn-based projects ongoing (this is also an apt metaphor for my PhD). Finally, California is a pretty neat place so I’ve gotten into photography in my time here so that I can document all the beautiful West Coast sights.

 

Fellows Feature: Alice Popejoy

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Alice is a public health geneticist and computational biologist, working at the intersections of evolutionary genomics, statistical genetics, and the ethical, legal, social implications (ELSI) of genomics research. Alice received her PhD in Public Health Genetics and Certificate in Statistical Genetics from the University of Washington. She is working on comparative evolutionary genomics as a CEHG Fellow, and as a postdoctoral scholar in the Bustamante Lab, she leads the Ancestry & Diversity Working Group of the Clinical Genome Resource (ClinGen) consortium.

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

Originally from Sacramento, I was fortunate to grow up in one of the world’s most diverse and integrated cities, with the largest urban tree canopy of any city in North America. I moved to upstate New York to attend Hamilton College, where I double-majored in Biology and French, took classes in Japanese and Religious Studies, and studied abroad for a year of full immersion in Paris. After college, the financial crisis combined with my desire to influence science policy led me to Washington, DC where I worked service industry jobs to support an unpaid internship in the U.S. House of Representatives. While giving tours of the Capitol and answering constituent phone calls, I landed a two-year Public Policy Fellowship at the Association for Women in Science (AWIS), where I worked with Congressional offices, the White House, professional organizations, and research institutes to advocate for programs to support diversity and inclusion in science, technology, engineering and mathematics (STEM). At AWIS, we also conducted research on gender representation among winners of scholarly awards and prizes, relative to the pool of qualified candidates and scholars, and found that women are over-represented among prize winners for service, teaching, and mentorship, whereas they are sorely under-recognized for academic research and scholarship.

Thanks to encouragement from accomplished female scientists at AWIS, I returned to academia to pursue my early interest in genetics and the law. At the University of Washington in Seattle, I earned a PhD in Public Health Genetics and a Certificate in Statistical Genetics, conducting several studies across comparative evolutionary genomics, statistical genetics, and ethical, legal, social implications (ELSI) of research. At UW, I served as the Graduate Student Body President and sat on the Board of Regents as well as several other high-profile committees, putting my public policy skills to work advocating for the needs of graduate and professional students. In my spare time, I learned Norwegian and, before graduating, spent six months as an International Research Fellow at the University of Oslo. Upon graduation, I was recruited to the Bustamante Lab in the Department of Biomedical Data Science at Stanford and have been a postdoctoral fellow here for the last year and a half. In addition to a CEHG Fellowship, I have affiliations with the Center for Integration of Research on Genetics and Ethics (CIRGE) at the Stanford Center for Biomedical Ethics (SCBE) and Stanford Precision Health for Ethnic and Racial Equity (SPHERE).

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

I remember visiting the American Museum of Natural History in New York City as a child and seeing an exhibit on the Human Genome Project. It highlighted the fact that humans are made up of the same stuff as fruit flies and bananas, and I remember thinking that was the most important thing I’d ever learned. If we were all connected to other species, including plants, then surely this information would help people realize that we are all one big family of humans. Later, while studying genetics in high school biology, I became obsessed with the idea that there should be lawyers who knew about DNA and the importance of genetic information for society.

When asked by adults what I wanted to be when I grew up (as children often are), I explained that my future career would involve ‘a field that doesn’t exist yet, at the intersections of genetics and the law’. Nearly a decade later, I began a PhD program in Public Health Genetics and continue to operate at the intersections of genetics and society.

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

As an interdisciplinary researcher, I have many projects that span multiple lines of inquiry. Related to computational and evolutionary genomics, I study light receptor genes called opsins, which are well-known as color vision photoreceptors in rods and cones of the retina, and lesser known as mysterious non-visual photoreceptors expressed throughout the body, especially in the brain and central nervous system. For the CEHG Fellowship, I am expanding on this work from my dissertation to study variation in opsins within and between human populations. Most people are generally surprised to find out that there are light receptors all over the human body and that we have no idea what they do. While other scientists tend to be more skeptical that non-visual opsins have retained their light-sensing function, most non-scientists are often intuitively comfortable that this makes sense, in theory.

My other primary focus is genetics and diversity, specifically how ‘race’, ‘ethnicity’, and ‘ancestry’ are interpreted and used in clinical genomics. I currently co-Chair with Carlos Bustamante the ClinGen Ancestry and Diversity Working Group (ADWG, https://www.clinicalgenome.org/working-groups/ancestry/) and we are collecting evidence to inform the development of guidelines for the use of diversity measures in clinical genomics and research.

The most common question I get asked about this research is whether we can simply do away with the collection of measures such as ‘race’ and ‘ethnicity’, in favor of inferring genetic ancestry and using that instead. The answer is that these issues are complicated, and the variables mentioned are capturing different kinds of information. For example, complex traits with both polygenic and environmental factors are likely influenced by background genetic architecture (often modeled by ancestry), and societal determinants of health (for which race or ethnicity are often used as a proxy). While many geneticists often think of diversity in genomics as an ethical issue, it is in fact a substantial scientific problem in terms of ascertainment and measurement bias, information disparity across populations, and inappropriate assumptions about the validity of using socio-cultural factors to model genetic background.

Why is your research important? What are the possible real world applications?

My research is important because all of the questions I ask center on challenging established assumptions about the world and the ways in which we conduct scientific research. For example, bacterial rhodopsin is in widespread use as a tool to study gene expression and other cellular mechanisms, but very little is known about the endogenous function of non-visual opsins in humans. Considering that light is the most ubiquitous source of life on Earth, and we are constantly inundated with synthetic photic signals in daily life (often paired with a chronic deficit of exposure to natural light), it is bizarre that so little attention is paid to this mysterious gene family. Similarly, terms such as ‘race’, ‘ethnicity’, and ‘ancestry’ are often used interchangeably and included as variables to correct for population structure in genetic association studies. However, there are important and complex differences between these concepts that often go unexamined. A lack of diverse representation in genomics research means that we actually know very little about the full range of human genomic variation that underlies disease etiology, and yet ‘precision medicine’ initiatives are rolling out in hospitals across the nation as if we have all of this figured out. The importance of what I’m doing across all of my projects is in the questioning of baseline assumptions that are often taken for granted – a practice that I feel is sorely missing from pedagogy these days.

What happens next in the process of discovery?

In my research, the process of discovery doesn’t just end and begin with the revelation of novel analytic and experimental findings. While dissemination in the form of academic papers is the norm, and this may be sufficient for some forms of discovery, it is essential that researchers whose work impacts people and populations focus on disseminating our findings in more meaningful and far-reaching ways. For example, the ClinGen Ancestry and Diversity Working Group is now conducting a survey of clinical genomics professionals and researchers to determine how ‘race’, ‘ethnicity’, and ‘ancestry’ are perceived and utilized for the purposes of variant interpretation and clinical care. Our findings from this survey will then be used in the development of guidelines for the use of diversity measures in clinical genomics. In this way, the results of our study are not only informative, they are also being used to improve the implementation of precision medicine.

Briefly, what’s the coolest thing about your work?

One of the coolest things about my work is how many different kinds of people from various disciplines are involved. The next step in my research on light receptors will involve collaborating with a quantum physicist, for example. In the context of my work on diversity in genetics, I regularly interface with statistical and population geneticists, clinical genetics professionals, bioethicists, and public health and health disparities researchers. The multi-disciplinary teams in which I’m involved enrich and deepen the research, while naturally expanding the reach of its impact.

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

I have had several mentors over the years who taught me valuable lessons both personally and professionally, each of them having contributed to my success in various ways. One in particular, Dr. Phoebe Starfield Leboy, is most notable for without her, I probably never would have even considered pursuing a PhD. Phoebe was a biochemist at UPenn and a past-President of the Association for Women in Science (AWIS) when I started working there in 2010. She was also the PI of an NSF-ADVANCE grant to look at scholarly awards and prizes in professional and disciplinary societies. The first day we met, Phoebe asked me what I wanted to do in life and how she could help me achieve it. She took me under her wing as an apprentice of sorts, both in terms of conducting analyses on her awards data and in terms of navigating science and the strange world of academic researchers as a young woman. She was also diagnosed with ALS (Lou Gehrig’s Disease) within the first ten days of our meeting, so the two years we worked together were the last two of her life. I think she felt it important to instill in me all of her knowledge and experience about what it was like to be a woman in science, and how to successfully navigate the barriers that naturally present themselves. As her final mentee out of dozens throughout her prolific career in academia, I feel extremely fortunate to have learned from her – not only how to think, write, and operate as a successful scientist, but also how to live a good life and appreciate every day as if it might be our last.

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

For any other postdocs or graduate students considering a similar educational path, I would emphasize the need to be comfortable with the unknown and ambiguous. In science, we so often wish to nail down precisely what we are going to do and how we are going to achieve it. When working on complex issues that span genomics and the ethical, legal, social implications (ELSI), as we do in Public Health Genetics, there are often unforeseen twists and turns with research projects that reflect a need for flexibility to accommodate stakeholder concerns, in addition to other ethical, legal, and social issues.

In addition to comfort with ambiguity, I strongly encourage persistence and a personal commitment to some values-based cause that drives the research forward. Despite all of the collaborative opportunities, interdisciplinary work can sometimes be solitary in that others who are entrenched in siloed departments and institutions may not always see the value in what you are doing. The bottom line is to never give up, even if it seems like you are the only one who cares, and to treat situations of misunderstanding as opportunities for teaching others about the importance of what you do, rather than as a sign that you should abandon all hope of living at the intersections and find a box to crawl into.

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

My future plans are to build a world-class academic research lab in Public Health Genomics, with training and research opportunities for young scholars interested in evolutionary genomics and ethical, legal, social implications (ELSI) of genomics research and technologies. In the next 5-10 years, I will ideally be on faculty at a University in Northern California, conducting cutting-edge research and training the next generation of Public Health Geneticists!

CEHG’s core values include “interdisciplinary research” and “collaboration.” Can you speak to the ways your work has embodied these values?

I feel like my research exemplifies CEHG’s core values of interdisciplinary research and collaboration, as these are two key pillars of everything that I do. In order to address the most complex and challenging questions of our time, it is essential to bring diverse stakeholders and researchers with a wide variety of expertise to the table. This diversity in perspectives not only makes our science better; it is also valuable from an ethical and social standpoint.

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

When I’m not working on research, I spend time with my family outdoors and especially enjoy hiking, skiing, rock climbing and parkour*. In addition to running, jumping, climbing, etc. that are involved in parkour, I also enjoy teaching the sport. I became a parkour instructor during graduate school in 2014 and have been committed to teaching people (especially women) ever since. Besides these athletic endeavors, I greatly enjoy a high-quality coffee shop and spending time in quiet contemplation, whether that is during yoga or sitting out in nature.

* – “Parkour is a training discipline using movement that developed from military obstacle course training. Practitioners aim to get from one point to another in a complex environment, without assistive equipment and in the fastest and most efficient way possible.” – wikipedia.com

Fellows Feature: Janet Song

Janet is a graduate student in David Kingsley’s lab,song7468_forweb where she is investigating genetic regions that might be involved in the evolution of the human brain. She received her B.A. in Chemical and Physical Biology from Harvard University in 2009.

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

I grew up in the suburbs outside of Philadelphia where I had a pretty normal childhood – attending our local Chinese church and cheering rabidly for the Philadelphia Eagles. As a high school student, I was fortunate to do summer internships at Drexel University, where I worked with Dr. Timothy Block on the early detection of cancer, and later with Dr. Gordon Harris and Dr. Marlene Oscar-Berman at Massachusetts General Hospital on brain volumetric differences in alcoholics. These early exposures to research drove my interest in genetics and molecular biology.

In college at Harvard, I worked with Dr. Jeffrey Macklis. His lab studies the development of the cerebral cortex. I focused on genes that control axon extension in corticospinal motor neurons, which reside in the brain and extend long processes into the spinal cord. These neurons control voluntary movement and are often damaged during spinal cord injury.

After college, I came to Stanford to pursue my PhD with David Kingsley. My early experiences with research had made me very interested in gene regulation: How do the same set of instructions encode all the cells in the body? How do mutations in the genetic code affect these instructions? As I entered graduate school, I was particularly interested in asking these types of questions in relation to evolution. I wanted to understand how a relatively small amount of change to the genome – most of which is not in the genes themselves, but rather in non-coding regions – can distinguish one species from another.

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

My parents, who both got PhDs in biology in the early 1990s, talked about PCR so much that one of my first words was actually “PCR”. Because of this, I like to say that I was destined to be a biologist from birth. However, the truth is that I was not that enamored with science as a kid. That all changed in sixth grade, when my science teacher announced that students could do science fair projects for extra credit. I promptly informed my mom that I would be participating in this endeavor and needed to buy some plants. She was horrified at the thought of our house besieged by sunflower plants grown under different conditions for months (the de facto sixth grade project) and suggested instead that I come to her lab for a few days. To sixth grade me, a few days of work sounded way better than growing plants for months, and I agreed.

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Images courtesy of Janet Song

There, I UV irradiated DNA at different wavelengths and for different amounts of time to see how much DNA damage it would cause. That was my first exposure to “real” science and I was hooked. I went on to do more science fair projects (Question: Which brand of sunscreen is the best at protecting against UV irradiation? Answer: Rite Aid) and later, participated in multiple summer research internship programs in high school. I went to college certain that I wanted to run my own research group one day and have not wavered from that path since.

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

I study a human-specific element in the third intron of the calcium channel gene, CACNA1C. We discovered that this genomic region is misannotated in the human reference genome and is composed of hundreds to thousands of 30 bp repeats, expanded from a single 30 bp sequence found in chimpanzees and other primates. Intriguingly, this human-specific tandem repeat is also variable within humans. We found that different sequence variants on the 30-mer motif are linked to nearby SNPs that have been repeatedly associated with bipolar disorder and schizophrenia.

Using enhancer reporter assays, we showed that the expanded human tandem repeat arrays drive significantly higher enhancer activity than the single 30-mer found in chimpanzees, and that human repeat arrays associated with psychiatric disease risk have decreased enhancer activity compared to other human repeat arrays. These results suggest that changes in the structure and sequence of these repeat arrays may have contributed to changes in CACNA1C function during human evolution and may modulate neuropsychiatric disease risk in modern human populations. (See our recently published manuscript for more details: https://www.cell.com/ajhg/pdf/S0002-9297(18)30238-6.pdf)

This tandem repeat may provide a key example of how genetic regions are involved in both evolution and in disease. Previously, hallmarks of human evolution, such as bipedalism or smaller jaws, have been linked to lower back problems and impacted wisdom teeth present in adult humans.

Our research provides a genetic example of how the rapid evolution of larger brains with increased complexity could have led to susceptibility to psychiatric disease.

We are now studying the effects of adding or removing this tandem repeat from CACNA1C on neural development, calcium signaling, and gene expression in mouse models and in human cultured cells. We hope that further study of this tandem repeat can clarify treatment options for individuals with bipolar disorder or schizophrenia and further characterize how novel DNA insertions can alter neural function both in evolution and in human disease.

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Briefly, what’s the coolest thing about your work?

My research has provided an example of how the same genetic regions involved in human evolution may also play a role in human disease. From my anthropocentric perspective, I often think of the regions in the genome that are unique to humans as “better” than other regions of the genome because they are responsible in aggregate for improved cognition in modern humans. However, it also makes evolutionary sense that regions under selection during human evolution may have inadvertently contributed to human disease. Compared to ancient genetic regions, regions diverged between humans and chimps have had less time to be refined in response to negative selective pressure and would be selected for if they have beneficial effects that outweigh the negative effects.

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

There are so many people who have helped me along this path. My parents have been instrumental to my development as an individual. From them, I gained a moral compass and learned the importance of hard work and determination. I have also had a variety of scientific mentors throughout the years, including my mother, Dr. Timothy Block, Dr. Jeff Macklis, Dr. Vibhu Sahni, and Dr. David Kingsley. They imparted and nurtured my passion for genetics and provided me with different examples of creative and rigorous scientists.

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

I still have a long way to go in my scientific journey, but here are some things I have learned so far:

  1. The most important attribute in research is perseverance, especially as an experimentalist. Many experiments will fail technically or give uninteresting results, but it is important to never lose that desire to try and try again.
  2. Science should be communal. Working with others can help you to avoid reinventing the wheel and allow you to iterate through scientific questions more quickly.
  3. Don’t be afraid to try new things! The best way to answer a question is not always with tools with which you are already familiar.

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

In a decade, I hope to be an assistant professor running my own research program centered on gene regulation. I have remained endlessly fascinated by how almost every living thing is encoded by the same molecule, DNA. Like many other geneticists, I am driven by the desire to understand how this deceivingly simple code can produce such a wide variety of complex organisms and how the same exact code can be interpreted differently within a single organism to produce neurons, T cells, bone, and all the other kinds of cells in the body.

CEHG’s core values include “interdisciplinary research” and “collaboration.” Can you speak to the ways your work has embodied these values or to their importance to your future work or past experience?

Collaborations combine the expertise of different individuals to best address a scientific question. I have been fortunate to collaborate both within the Kingsley lab and with other labs. The main project I am working on (see earlier answers) started as a collaboration with Craig Lowe in the Kingsley lab. Craig performed a screen for regions of the human genome that are unique to humans and overlap chromatin marks indicative of regulatory activity. One of the regions he identified was the human-specific repeat element that we then went on to study further. As this project evolved toward approaches outside of our areas of expertise, we began collaborations with a number of other labs at Stanford – including Sergiu Pasca’s lab to differentiate stem cells into 3D brain organoids, Paul Khavari’s lab to identify the transcription factors that bind to different repeat variants, and Alistair Boettiger’s lab to probe the chromosome structure at our region of interest. These collaborations have allowed us to use a variety of approaches to more efficiently answer questions about the function of this repeat element.

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

When I’m not working on research, I enjoy cheering for my hometown Philadelphia Eagles, playing cards and board games, and attending musicals. I recently bought a pair of rollerblades and have been slowly learning to rollerblade around Stanford. I’m still very much a beginner, but I hope to be able to rollerblade to and from lab one day!

Fellows Feature: Daniel Hornburg

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Daniel is a postdoctoral scholar in Mike Snyder’s Lab on Stanford campus, working to discover personalized molecular fingerprints across omes, opening up new avenues to define health and disease phenotypes and predict personalized disease trajectories. He received his Ph.D. from Max Planck Institute of Biochemistry/ LMU in 2015, and earned his M.S. at Technical University of Munich in 2010.  

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

Science makes me a great chef, but not because I follow the recipes… more to that later. I am Dan, a postdoc in Mike Snyder’s Lab. I received my Bachelor and Master’s degree in Molecular Biotechnology from the Technical University of Munich (TUM) in Germany. While I was conducting my master studies, I also worked on a startup in which we developed multi-enzyme complexes from extremophile bacteria to degrade biomass efficiently for use in biotech.

After my studies at the TUM, I joined Matthias Mann at the Max Planck Institute of Biochemistry for my PhD. In the Mann lab, I developed proteomics strategies to investigate neurodegenerative diseases. Since I am a biochemist by training, I started my PhD with some wet lab work but after the first year, I began to operate various mass spectrometers and ended up with complex proteomics datasets. This was a great opportunity to learn and establish data analysis strategies in the field of neuroproteomics. Since then, I love to do both and the best percentage for me is 20% experimentalist, 80% data scientist.

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

As long as I can think back, I have been curious. There is hardly anything more mind-blowing than thinking about the scale of the universe, or the complexity of life. If you talk to my grandparents, they will tell you about a 5-year old boy who tells everyone that he is going to be an astronaut or scientist (I am not implying that an astronaut cannot be a scientist, but I did not have such a nuanced view on job opportunities back then).

Science provides us with a unique perk that allows seeing so much more of the world. If you look at the night sky, you see hundreds of stars. Isn’t it fascinating that the photons hitting your retina started their journey millions of years ago, which means you look back into the past on the very same scale? These photons excite molecules in your Rod cells, starting a signal transduction cascade giving you the feeling of wonder and excitement in the first place. On top of that, some other molecular processes make you think about that or type these words… For me, that experience is addictive and I am glad that we live in a time and socioeconomic context where we have access to the tools to explore the beautiful complexity of nature.

Beyond that, I quickly realized that reason and science are the best tools to fix problems and will be key to making the world a better place. There is a nice quote from Neil deGrasse Tyson that brings it to the point:

Any time scientists disagree, it’s because we have insufficient data. Then we can agree on what kind of data to get; we get the data; and the data solves the problem. Either I’m right, or you’re right, or we’re both wrong. And we move on. That kind of conflict resolution does not exist in politics or religion.

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

An asteroid is about to hit Earth. Why is it useful to know that 10 years ahead, instead of one day before it happens? First, knowing it 10 years in advance gives us more time to do something about it. Second, while we would need to massively interfere with its trajectory a day before it impacts, it only takes a gentle poke 10 years earlier to change its path by an iota of a degree to prevent a disaster.

I am convinced the same holds true in biomedicine. Think about devastating chronic diseases, such as diabetes or Alzheimer’s: When a patient shows symptoms, the damage is done. We cannot cure it. What if we could identify and understand molecular deteriorations 10 years earlier and a minor, personalized intervention is sufficient to prevent the diseases from happening?

This is my research mission. I develop biochemical, mass spectrometry, and computational strategies to characterize thousands of molecules from small amounts of biological samples (e.g. blood) to discover and characterize molecular alterations to predict disease trajectories at an early stage. I have been working for 7 years in proteomics and when I joined Stanford, I wanted to expand my omics expertise with another molecular layer. That is why I am now responsible for the lipidomics in the lab and I explore the function of lipids in human physiology and their role in diseases.

Lipids are a complex, yet largely unexplored, molecular family with thousands of individual species. A growing body of evidence suggests that lipids are involved in a variety of physiological processes beyond energy metabolism. This includes key roles as molecular precursors for hormones, structural elements, transporters, or signaling molecules. Alarmingly, more than 70 % of adults show abnormal lipid metabolism (dyslipidemia), which results in an altered lipid concentration in the blood and is associated with chronic metabolic conditions, including diabetes and cardiovascular diseases.

When I started in the Snyder lab a year ago, I established a targeted lipidomics pipeline. I spent the first months optimizing biochemical protocols and the mass spectrometer to extract, identify, and reliably quantify lipids from bio specimens. Now, we can measure close to 1000 lipids across 100 samples in less than 2 days.

Since then, my focus has been to develop and employ computational strategies to interpret alterations I observe in the lipidome; for instance, comparing healthy and pre-diabetic people performing an exhaustive cardiopulmonary exercise. To this end, I integrate: i) known biological functions of individual lipid molecules; ii) specific biochemical properties (including the degree of saturation, fatty acid chain length etc.); and iii) information on how these lipids connect to other molecules, such as processing enzymes.

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All post images and figures provided by Daniel Hornburg.

Ultimately, we aim to identify not only early biomarkers but also to further our molecular understanding of disease mechanisms by being able to follow disease trajectories over time, on a personalized level.

Briefly, what’s the coolest thing about your work?

I think it is pretty cool to monitor thousands of molecules from a small drop of blood. In particular, I like our inverted research approach. Instead of starting with a narrow hypothesis, I observe complex molecular changes through mass spectrometry and interpret these alterations, using tailored computational strategies. Based on that data, I formulate a falsifiable hypothesis that I can test in close collaboration with a great team of scientists from various disciplines. Another cool thing is the coding itself. I can code from anywhere. I recommend the combination of laptop, hot coffee, and ocean view. 🙂

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

That starts with my family that never got tired of supporting curiosity and exploration. Beyond that, I have been blessed to work with great scientists like Matthias Mann, Felix Meissner, Jurgen Cox, Dieter Langosch, Harald Luksch and, of course, Mike Snyder. Moreover, throughout my career, I worked with friends at the same career stage. All these interactions contributed, and are still contributing, to my personal and professional development and I wouldn’t be where I am without them.

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

I am a passionate advocate of interdisciplinary and collaborative research for two reasons. First, it is undoubtedly more fun and helps you get through all the ups and downs. Second, having many brains working on a problem makes it more likely to come up with a solution.

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I think research will increasingly depend on collaborative efforts. For instance, if you want to establish a molecular landscape of health this cannot be done without a collaborative interdisciplinary team. Thus, fostering a collaborative scientific network is one key ingredient for success. That said, I think we have to rethink some of the core policies in academia in order to provide the optimal environment to motivate flourishing collaborations across large teams. This is one of the major challenges academia faces, which is why I have expressed my opinion on authorship policies in a blog and correspondence.

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

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If it is applicable to your field of research, I recommend becoming proficient at both, biochemistry/biology and data analysis. An in-depth biochemical understanding is key to devising and interpreting lab experiments. In turn, knowing how to deal with the data helps you in designing the right experiment in the first place and efficiently analyzing and disseminating your results. Moreover, more often than not, experiments fail and we don’t even know why since the underlying variables of the biological system are underdetermined. This will be frustrating from time to time. It can be very refreshing to work on bioinformatics. Coding is more deterministic and each hour you invest, you learn and/or progress.

Finally, always remember what you like and what you don’t like in science (and life). You might not be able to make a change right now, but the time can come when it is your responsibility to remember and be that great mentor or the devoted voice to advocate for improving our (scientific) community.

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

In the long run, I woud like to lead an interdisciplinary and collaborative team that expands our understanding of the biomolecular world and makes a difference. Whether this is in academia, a start-up or industry depends on how things are developing. I keep an open mind and explore opportunities across these three fields. Conceptually, I love academic science and teaching, but success in academia involves many random variables such as: Are you lucky with getting positive results in a timely manner that will result in papers with the “right” author position? I‘ll reflect on my opportunities and select for inspiring environments, cool people and exciting topics. For me, that is the best way to be happy and successful and there are usually more opportunities than there is 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?

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I love doing sports like jujitsu and biking. This is a great way to free my mind. I also like cooking. The “special talent” in that context is that I can endure hunger for hours. This is important: It motivates me to get started and gives enough time to craft a delicious meal. Perhaps delayed gratification is something you acquire during a scientific career.

Besides that, I am a passionate advocate for science and reason. I am convinced that science provides the best toolset to learn from the past, understand the present and shape the future and, thus, is useful beyond academic research.