Get to know the TAGC 2020 Keynote Speakers through our interview series.

Cassandra Extavour

Cassandra Extavour obtained an Honors BSc at the University of Toronto with a specialist in Molecular Genetics and Molecular Biology. She obtained her PhD with Antonio Garcia Bellido at the Severo Ochoa Center for Molecular Biology at the Autonomous University of Madrid. She performed postdoctoral work first with Michalis Averof at the Institute for Molecular Biology and Biotechnology in Crete, Greece, and subsequently with Michael Akam at the University of Cambridge. At Cambridge she received a BBSRC Research Grant and became a Research Associate in the Department of Zoology. In 2007, she established her independent laboratory as an Assistant Professor in the Department of Organismic and Evolutionary Biology at Harvard University, where she was promoted to Associate Professor in 2011 and to Full Professor in 2014. She has received numerous honors and awards and has been nominated for the Joseph R. Levenson Memorial Teaching Prize and the Harvard Graduate Women in Science and Engineering Mentoring Award. The Extavour laboratory is interested in understanding early embryonic development, the genes that control this development, the evolutionary origins of these genes, and how their functions have changed over evolutionary time.

What research are you most excited about right now, and why?

I’m excited about research in genetics that tries to bring together our understanding of the function and evolution of genetic control systems across multiple scales of biological organization. An example might be the genetic circuits that control the shape of cells within a multicellular group—and how those individual cell shapes get connected and propagated to result in changes in the shape of the whole group of cells. Another example is investigating how the action of individual genes in a gene regulatory network is parallelled across branches of the evolutionary tree of life—and how genetic regulatory interactions in one lineage of the tree of life can be used to predict how interactions work in other lineages. 

I’m interested in these cross-scale studies because I think this is the only way we’re going to move toward a comprehensive understanding of the evolution of these genetic systems; the one-by-one, gene-by-gene, cell-by-cell approach is critical, but it can’t be the only approach. It was so fruitful for the last half of the last century, but now systems-level, global genomic-level, and population-level data are becoming possible to generate and analyze, which can move us beyond what was possible last century.

What do you like about working with flies and other insects?

There is no better genetic manipulation system in an animal than in Drosophila melanogaster. No other animal can be manipulated genetically with the same precision and control, so for someone who wants to work on the genetic control of obligately multicellular systems, it’s the best model.

From a comparative evolutionary point of view, the genus Drosophila is large as far as insects go. It’s as old as many other genera, but it’s experienced a lot of rapid radiation. It has several thousand species, and at least a thousand of those evolved, we think, from a last common ancestor within the last few tens of million years ago, which is extremely quickly. There is a huge amount of species diversity, genetic diversity, and morphological diversity ranging from very recent evolutionary timescales to much older evolutionary timescales just within the genus Drosophila, which is also very appealing to me.

Is there anything about yourself or the field that made you feel like you didn’t belong in science? What would you say to early career scientists struggling with the same feeling?

Absolutely: being a woman in a male-dominated field, being black in a white-dominated field, being gay in a heteronormative-dominated field. I feel like I belong, but on a daily basis, I’m reminded that not everybody thinks that.

What I would say to early career scientists is that feeling fascinated by genetics and wanting to be a geneticist means that you belong in genetics—but it’s a reality that not everyone you encounter in your career is going to share that view. Academia—scholarly research of any kind, including science—is a very conservative profession with narrow definitions of success, belonging, and what it takes to participate in and contribute to the field.

What I recommend to early career researchers is that they work on developing and strengthening as many different resources as they can in their lives to remind them that they have a right to do and pursue whatever they want to—because they may not always find that support within the genetics field.

TAGC aims to foster collaboration between communities and disciplines. Can you give an example of a collaboration that really helped your work?

In the last few years, we wanted to expand beyond Drosophila melanogaster into looking at the biology and genetics of Drosophila species endemic to the Hawaiian islands. What was critical to the success of that work was establishing great collaborations with scientists working in Hawaii who knew the ecology and the biology of the animals and plants that are native to those island systems and who were willing share their knowledge with us, helping us understand the ecological context of these files. That’s the only way—not only to literally find and catch the flies so you can study them—but to make sense of the biology and genetics of those flies. When you want to branch into new areas of zoology and explore new habitats in the world, collaborations with people who know the biology give you context to understand the genetics you’re interested in. So that’s been a very successful collaboration, and we’re very grateful to Karl Magnacca, Steve Montgomery, Ken Kaneshiro, and Don Price. They’ve been working with these flies in Hawaii for many years, and they were absolutely critical to our ability to learn about them.

Another successful collaboration, not in genetics, but on early development and embryology in a gene-free context was with applied mathematicians Chris Rycroft and Jordan Hoffmann in our engineering school at Harvard. They helped us apply mathematical modeling to the behavior of nuclei in early embryos to give us new hypotheses to test with molecular and genetic tools about how these embryos put themselves together.

Select Publications from the Extavour Lab

Bacterial contribution to genesis of the novel germ line determinant oskar
Blondel L, Jones TEM, Extavour CG
Elife. 2020 Feb 24;9. pii: e45539. doi: 10.7554/eLife.45539

Absence of a Faster-X Effect in Beetles (Tribolium, Coleoptera)
Whittle CA, Kulkarni A, Extavour CG
G3 (Bethesda). 2020 Jan 27. pii: g3.401074.2020. doi: 10.1534/g3.120.401074

Topology-driven analysis of protein-protein interaction networks detects functional genetic modules regulating reproductive capacity
Kumar T, Blondel L,  Extavour CG
bioRxiv.  doi: 10.1101/852897 (preprint posted November 30, 2019)

Insect egg size and shape evolve with ecology but not developmental rate
Church SH, Donoughe S, de Medeiros BAS, Extavour CG
Nature. 2019 Jul;571(7763):58-62. doi: 10.1038/s41586-019-1302-4

Reproductive Capacity Evolves in Response to Ecology through Common Changes in Cell Number in Hawaiian Drosophila
Sarikaya DP, Church SH, Lagomarsino LP, Magnacca KN, Montgomery SL, Price DK, Kaneshiro KY, Extavour CG
Curr Biol. 2019 Jun 3;29(11):1877-1884.e6. doi: 10.1016/j.cub.2019.04.063

Get to know the TAGC 2020 Keynote Speakers through our interview series.

Jon R. Lorsch

Jon R. Lorsch is the director of the National Institute of General Medical Sciences (NIGMS). In this position, Lorsch oversees the Institute’s $2.9​ billion budget, which supports basic research that increases understanding of biological processes and lays the foundation for advances in disease diagnosis, treatment, and prevention. A leader in RNA biology, Lorsch studies the initiation of translation, a major step in controlling how genes are expressed. When this process goes awry, viral infection, neurodegenerative diseases and cancer can result. To dissect the mechanics of translation initiation, Lorsch and collaborators developed a yeast-based system and a wide variety of biochemical and biophysical methods. Lorsch continues this research as a tenured investigator in the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development.

What research are you most excited about right now, and why?

That’s a broad question! If I had to single out one area, I’d say that studies of regeneration in different organisms are extremely exciting—asking how organisms regenerate entire limbs, organs, or body plans as adults. It’s not something my lab works on, but I find it very interesting.

What do you like about working with yeast?

You can grow a lot of them, which is very helpful for a biochemist.

Is there anything about yourself or the field that made you feel like you didn’t belong in science? What would you say to early career scientists struggling with the same feeling?

I think imposter syndrome is a very common feeling that many—maybe even most—people have, and it doesn’t just happen in science. I think the main thing is to remind yourself that you do belong in science. Keep following what your passion is, and figure out how to move forward in the way that works best for you.

TAGC aims to foster collaboration between communities and disciplines. Can you give an example of a collaboration that really helped your work?

I’ve collaborated with Alan Hinnebusch at the National Institute of Child Health and Human Development for 20 years and continue to do so today. It has absolutely been one of the highlights of my career. Alan is a world-renowned yeast geneticist. Bridging the gap between the in vivo side using his yeast genetic expertise and the in vitro biochemistry we can do has proven extremely rewarding in terms of understanding the mechanisms involved in eukaryotic translation initiation.

Get to know the TAGC 2020 Keynote Speakers through our interview series.

Sue Biggins

Sue Biggins studies the mechanisms that ensure accurate chromosome segregation and regulation of the cell cycle. Her lab achieved the first isolation of kinetochores and has been applying structural, biophysical and biochemical techniques to elucidate the mechanisms of kinetochore-microtubule interactions and spindle checkpoint regulation. Her lab also works on the mechanisms that ensure chromatin composition and centromere identity. Biggins is currently a Senior Vice President and the Director of Basic Sciences at the Fred Hutchinson Cancer Research Center and an Investigator of the Howard Hughes Medical Institute.

What research are you most excited about right now, and why?

In terms of the chromosome segregation field and work on the kinetochore, we’ve now identified most of the parts of the machine. That was 20 years’ worth of work, identifying components and figuring out who interacts with whom. We’re at the exciting moment now of figuring out how the machine works. The kinetochore itself has many dynamic and diverse functions, and now we can ask which proteins do what functions. The field is at a great moment now, starting from a better understanding of the structure to get at the dynamics of the complex.

Everything gets stuck until there’s a new technological advance. In my field, it’s been the integration of everything: cryo-EM, biophysics, advanced cell biology, light microscopy, CRISPR-driven genetic screens. It’s an exciting time.

What do you like about working with yeast?

Funnily, we started working on human cells recently. But yeast has been the foundation of my career because of its simplicity and all of the things you hear about it as a genetic organism. I was really trained as a geneticist, and yeast has the simplest version of the process I study; there are some unique features that make it much more tractable. In yeast, there is a single microtubule that binds the kinetochore, whereas other organisms have many microtubules, so that simplifies things. Yeast have a very unusual centromere, which is sequence defined; most organisms have an epigenetically-based centromere. Some might argue that these are specialties that make yeast not relevant, but that hasn’t been true. We’ve identified a number of paradigms in yeast that have been conserved, despite these differences. And the simplicity of the system was a huge advantage. We knew the parts in yeast much earlier than in other organisms, and yeast has fewer components. The bulk of the proteins are conserved, and so are the functions.

Is there anything about yourself or the field that made you feel like you didn’t belong in science? What would you say to early career scientists struggling with the same feeling?

Like all women, I’ve faced some challenges. I was a bit naive when I came in; I thought it was something science had overcome. When I started in science and got a job, I felt like, “If they’re hiring me, they don’t have problems with women.” But as I moved on in my career, I could see the larger picture.

The needle on promoting women and underrepresented minorities in science did not move how I thought it would over the last 20 years. Looking back at it and recognizing that I made it through somehow definitely puts me on the lookout to try to help junior people so that they don’t face similar barriers.

If there are times when you feel you don’t belong or can’t do the work, remember that a lot of people go through that. It’s hard not to question yourself. I think the best thing you can do is to find a mentor and advocate—it doesn’t have to be someone in your field—who has gone through similar things to what you’re going through and find out how they got through it. That’s how I got through things.

My other key piece of advice is: don’t think that there is just one mentor. Mentoring is a spectrum, and every issue you face might require a different mentor. You might think “If I can just find my mentor, they’ll shepherd me through everything,” but it doesn’t work that way. I strongly suggest identifying the issue you’re facing and finding a mentor for that issue. Don’t assume that there’s one person who can answer everything.

TAGC aims to foster collaboration between communities and disciplines. Can you give an example of a collaboration that really helped your work?

Everything I do is completely made possible by collaboration. Chip Asbury has been my collaborator for over a decade, and our collaboration has allowed me to do things I couldn’t have imagined doing otherwise. We were able to do some biochemistry that moved the field forward, but the key thing has been combining it with biophysics. A lot of what we do is possible through collaboration with biophysicists.

There are so many advances in technology making things happen, but it’s very difficult to be an expert in all of them. The best way to be successful is to team up with the right people who know how to do what you don’t.

Select Publications from the Biggins Lab

Kinetochore-associated Stu2 promotes chromosome biorientation in vivo
Miller MP, Evans RK, Zelter A, Geyer EA, MacCoss MJ, Rice LM, Davis TN, Asbury CL, Biggins S
PLoS Genet. 2019 Oct 4;15(10):e1008423. doi: 10.1371/journal.pgen.1008423

An assay for de novo kinetochore assembly reveals a key role for the CENP-T pathway in budding yeast
Lang J, Barber A, Biggins S
Elife. 2018 Aug 17;7. pii: e37819. doi: 10.7554/eLife.37819

A TOG Protein Confers Tension Sensitivity to Kinetochore-Microtubule Attachments
Miller MP, Asbury CL, Biggins S
Cell. 2016 Jun 2;165(6):1428-1439. doi: 10.1016/j.cell.2016.04.030

The structure of purified kinetochores reveals multiple microtubule-attachment sites
Gonen S, Akiyoshi B, Iadanza MG, Shi D, Duggan N, Biggins S, Gonen T
Nat Struct Mol Biol. 2012 Sep;19(9):925-9. doi: 10.1038/nsmb.2358

Tension directly stabilizes reconstituted kinetochore-microtubule attachments
Akiyoshi B, Sarangapani KK, Powers AF, Nelson CR, Reichow SL, Arellano-Santoyo H, Gonen T, Ranish JA, Asbury CL, Biggins S
Nature. 2010 Nov 25;468(7323):576-9. doi: 10.1038/nature09594

Get to know the TAGC 2020 Keynote Speakers through our interview series.

Abby Dernburg

Abby Dernburg investigates how genetic information is transmitted from parents to progeny through the specialized cell division of meiosis. She received the Larry Sandler Memorial Award (from GSA’s Annual Drosophila Research Conference) for her graduate work with John Sedat at UCSF, where she explored diverse questions in chromosome biology. Her postdoctoral work with GSA Medal recipient Anne Villeneuve helped to establish C. elegans as a leading model organism for molecular genetic analysis of meiosis. Since 2001 she has led a research group at Lawrence Berkeley National Laboratory and UC Berkeley, where she was also an undergraduate. She has been an HHMI Investigator since 2008.

What research are you most excited about right now, and why?

There’s a question I’ve always wanted to answer that we’re finally making progress toward, which is the very long-standing mystery of how chromosomes recognize each other during meiosis. We had to wait until we had both the technology and the conceptual framework to enable us to address the question. I think those are both there now, finally letting us attack the question head on. So much is still unknown, but that makes it fun for me because I don’t know what we’ll find.

What do you like about working with C. elegans?

I see myself more as a chromosome person than someone who works with a particular organism. That’s one reason I’m very excited about TAGC: the opportunity to interact with lots of different model organism people. There’s a lot of synergy between what you can do in different systems. We mostly work with C. elegans, but we’re also developing a secondary model by developing tools to study recombination and meiosis in P. pacificus, which shows surprising differences in what we think of as core aspects of this process. By comparing these different nematodes, we see how plastic these mechanisms are by how they are modified during evolution. It helps to avert an absolutist mindset.

Is there anything about yourself or the field that made you feel like you didn’t belong in science? What would you say to early career scientists struggling with the same feeling?

I didn’t know if I was going to go on in academia—or if I even had the potential—until very late in grad school. I worry that students today feel pressure to sort it out too early. I was relatively comfortable with the ambiguity, which I realize was a kind of privilege. Obviously, I did decide to go on, but not with great conviction or certainty. It just never became the wrong path. I sometimes feel funny when I’m asked for career advice. In a way, you become an academic by not making choices, so I haven’t really experienced other potential futures.

TAGC aims to foster collaboration between communities and disciplines. Can you give an example of a collaboration that really helped your work?

When I started grad school, I wanted to become a crystallographer. I left that path early on when I fell in love with microscopy and chromosomes. But my most exciting collaboration in recent years has been with a crystallographer: Kevin Corbett, who I knew when he was a PhD student at Berkeley. He became a structural biologist with a focus on meiosis, which is what we work on, so it was a nice convergence of interests that led us to collaborate. It’s been a very productive collaboration, and I hope to do more of this in the future.

One thing that’s really changed in genetic research and model organism studies is the ability to do genome editing. We can now do much more detailed structure/function studies in model organisms than we have been able to do in the past, and having structural information about the proteins we work on enables us to develop specific hypotheses and test them in vivo. That’s a lot of fun.

Select Publications from the Dernburg Lab

A compartmentalized signaling network mediates crossover control in meiosis
Zhang L, Köhler S, Rillo-Bohn R, Dernburg AF
Elife. 2018 Mar 9;7. pii: e30789. doi: 10.7554/eLife.30789

Superresolution microscopy reveals the three-dimensional organization of meiotic chromosome axes in intact Caenorhabditis elegans tissue
Köhler S, Wojcik M, Xu K, Dernburg AF
Proc Natl Acad Sci U S A. 2017 Jun 13;114(24):E4734-E4743. doi: 10.1073/pnas.1702312114

The synaptonemal complex has liquid crystalline properties and spatially regulates meiotic recombination factors
Rog O, Köhler S, Dernburg AF
Elife. 2017 Jan 3;6. pii: e21455. doi: 10.7554/eLife.21455

The auxin-inducible degradation (AID) system enables versatile conditional protein depletion in C. elegans
Zhang L, Ward JD, Cheng Z, Dernburg AF
Development. 2015 Dec 15;142(24):4374-84. doi: 10.1242/dev.129635

The Chromosome Axis Mediates Feedback Control of CHK-2 to Ensure Crossover Formation in C. elegans
Kim Y, Kostow N, Dernburg AF
Dev Cell. 2015 Oct 26;35(2):247-61. doi: 10.1016/j.devcel.2015.09.021

Get to know the TAGC 2020 Keynote Speakers through our interview series.

Keith Yamamoto

Keith Yamamoto is Vice Chancellor for Science Policy and Strategy and Director of Precision Medicine at UCSF. After earning a PhD at Princeton, he came to UCSF in 1973. He served as chair of the Department of Cellular and Molecular Pharmacology from 1994 to 2003 and as Vice Dean for Research in the School of Medicine from 2002 to 2015. Yamamoto has long been an international leader in studying the mechanisms of signaling and gene regulation by intracellular receptors; he closed his research laboratory in October of 2019. 

Has the process of closing down your lab affected your research interests? What research are you most excited about right now, and why?

We’ve been pursuing a set of big research questions for 43 years in my lab. We’re writing seven papers right now, so the work still feels very current. I’m really excited that we have reached a new level of understanding about how cell and physiologic context drives differential gene expression networks; transcription patterns are precise in a given context yet highly plastic from context to context. Gaining a foothold on how cells and organisms solve this paradox provides insight into many interesting biological processes and biomedical concerns. 

What did you like about working with C. elegans?

Unparalleled genetic accessibility for a metazoan. It has a small, compact genome, and it’s a self-fertilizing hermaphrodite. These characteristics open up questions—and approaches to answering them—at an entirely different level.

As a grad student working with mammalian cells and tissues, I was nevertheless very tuned in to bacteriophage lambda genetics. I felt that phage lambda was the most “intellectually elegant” biological system because it seemed that a brilliant lambda geneticist could, in the morning, dream up a beautiful experiment to address a consequential research question, plate out bacteria and phage in the afternoon, and the next morning, check out the plates and have an answer! Okay, it wasn’t exactly that simple, but you get the idea. And among metazoans, C. elegans has a similar elegance; it’s experimentally approachable in ways that are intellectually pleasing and potentially rewarding. It’s a sort of “grown up” lambda phage.

For the past 15 years, we’ve toggled back and forth between mammalian and C. elegans work in the lab. What we’ve learned in worms has almost always informed our mammalian studies.

Is there anything about yourself or the field that made you feel like you didn’t belong in science? What would you say to early career scientists struggling with the same feeling?

I have two examples. 

First: as an undergraduate freshman, I declared a major in biochemistry, but I didn’t start working in the lab until my sophomore year. Before that, I called my dad, who was very happy about me training in science. I told him I was having fun in a creative writing course and was thinking of transferring to become an English major. 

I thought science was interesting, but it seemed like a totally isolated endeavor. I was imagining being trained and then going off by myself to the corner of a dark laboratory, staring into a microscope and never talking to anybody again. I thought, “I’m really a social person; I want to be able to interact with people, so that must mean that science is not for me.” Well, my dad talked me off that ledge, and once I started working in the lab, I learned that science is an enormously social endeavor—that doing science well, and enjoying it, depends strongly on interacting effectively with others.

The second example came at the beginning of graduate school. I’d migrated from a large midwestern state university to Princeton, where many of my classmates were from high-powered programs in the Ivy league and elsewhere. I felt totally out of it—I thought that I’d never overcome the big headstart that they appeared to have. In fact, of course, learning factual scientific information from well-known scientists is great, but it’s a pretty small part of becoming a successful scientist. More significant are learning to recognize important problems, breaking them into experiment-sized pieces, and deciding which results to pursue. Those are the skills you acquire in the actual doing of science, and good mentoring in graduate school—which I got from Bruce Alberts—is critical for building and using those skills. I think it’s not so uncommon for people from non-traditional backgrounds to perceive barriers to their success in science. But catching up is not hard to do if you work hard, and diversity of background and experience enriches scientific thinking and doing.

TAGC aims to foster collaboration between communities and disciplines. Can you give an example of a collaboration that really helped your work?

I’ll give you two. One was with the late Ira Herskowitz, who was a dear friend and someone I recruited to UCSF. As a graduate student, Ira was a terrific lambda geneticist, and he later became a 24/7 proponent for yeast genetics. I was deeply jealous of the level of genetic access and ease of experimentation in yeast compared to the cell culture work that I was doing. As soon as we cloned the mammalian glucocorticoid receptor, I begged Ira to teach us how to put it into yeast to see if it would function—he did, and it did! So we proceeded to do yeast genetics on a mammalian protein. Our collaboration revealed the functional interaction of the glucocorticoid receptor with the Swi/Snf chromatin remodeling complex. This was the first hint that metazoan transcriptional regulators acquire their activities by physical association with coregulatory factors, which was later confirmed with mammalian chromatin remodelers.

A second important collaboration was with the late Paul Sigler, who was a marvelous crystallographer. At a symposium at the University of Wisconsin in 1988 or ‘89, Paul and I were sitting on the Terrace, drinking beer, and talking about what needed to be done to better understand how transcriptional regulatory factors were working. That conversation launched a joint effort in which we solved the structure of the DNA binding domain of the glucocorticoid receptor in complex with its sequence-specific DNA motif. That started us on a long, exciting, and rewarding series of molecular structure-function studies.

Collaborations are fun because you establish close interactions with new people, and they’re exciting because you expand the range of concepts and technologies that you can apply to your problems of interest.

Selected Publications from the Yamamoto Lab

Roles of SWI1, SWI2, and SWI3 proteins for transcriptional enhancement by steroid receptors
Yoshinaga SK, Peterson CL, Herskowitz I, Yamamoto KR
Science. 1992 Dec 4;258(5088):1598-604

Nuclear Hormone Receptor NHR-49 Controls Fat Consumption and Fatty Acid Composition in C. elegans
Van Gilst MR, Hadjivassiliou H, Jolly A, Yamamoto KR
PLoS Biol. 2005 Feb;3(2):e53

Sumoylated NHR-25/NR5A regulates cell fate during C. elegans vulval development
Ward JD, Bojanala N, Bernal T, Ashrafi K, Asahina M, Yamamoto KR
PLoS Genet. 2013;9(12):e1003992. doi: 10.1371/journal.pgen.1003992

Germline signals deploy NHR-49/PPARa to modulate fatty-acid b-oxidation and desaturation in somatic tissues of C. elegans
Ratnappan R, Amrit FR, Ward J, Gill H, Holden K, Chen S-W, Olsen CP, Yamamoto KR, Ghazi A
PLoS Genetics. 2014 Dec 4;10(12):e1004829. doi: 10.1371/journal.pgen.1004829 

Glucocorticoid receptor control of transcription: precision and plasticity via allostery
Weikum ER, Knuesel MT, Ortlund EA, Yamamoto KR
Nat Rev Mol Cell Biol. 2017 Mar;18(3):159-174. doi: 10.1038/nrm.2016.152

Get to know the TAGC 2020 Keynote Speakers through our interview series.

John Wallingford

John Wallingford is a William and Gwyn Shive Endowed Professor of Molecular Biosciences at the University of Texas at Austin. Currently at the Wallingford Lab, he and his team combine in vivo imaging with systems biology to explore the cell biological basis of embryonic development.

What research are you most excited about right now, and why?

I’m excited about the breaking down of barriers. Increasingly, there’s no such thing as cell biology, developmental biology, microbiology, or genetics. These terms are useful for your identity, but they don’t reflect how we do biology now. I’m most excited about where you see big crossover between disciplines; in my lab, that’s predominantly a blurring of the lines between cell and developmental biology. 

I love the recent work on how microbiomes are impacting the development of the digestive tracts of vertebrates; many microbes are now known to send chemical signals that influence the development and differentiation of animals. I’m also excited about the interface of physics and developmental biology—a lot of work on tissue morphogenesis is really blurring those lines. And I’m excited about ecologists coming in and asking questions about developmental biology in wild mice as opposed to lab mice. So these things that blur the lines between disciplines are what’s most exciting to me these days.

What do you like about working with Xenopus?

It’s fast and cheap! I’m a data junkie, and one of the great things about Xenopus is you can move very quickly. If you come up with a harebrained scheme, you can put it into action and get an answer in less than a week sometimes. I really enjoy that aspect. You can tear through hypotheses really quickly. 

I also love imaging. People say, “Oh, you can’t image in Xenopus, it’s opaque,” but that’s ridiculous. My entire career has been built on imaging Xenopus. You just have to think about what you want to do. If you want to image deep into an intact animal at early stages, no, it doesn’t work that well. But a great thing about amphibians is that you can explant anything. You can put whatever tissue you want directly against the coverglass, and the cells are enormous. That lets you dig into subcellular behaviors as they occur in the embryo, which is what I’m interested in. Xenopus is an outstanding model system for that.

So many model organisms are so well established, it’s not unthinkable to jump from one system to another. My lab mostly uses Xenopus, but about a third of the lab works with mice. We’ve also done work with worms, and we’re in the process of getting Chlamydomonas up and running. The infrastructure for model organisms is so good now that if the tool in your animal isn’t good, just get another animal!

Is there anything about yourself or the field that made you feel like you didn’t belong in science? What would you say to early career scientists struggling with the same feeling?

The biggest hurdles I faced as a young scientist were my own mental health issues, which I dealt with poorly. I avoided therapy then, but I would encourage folks to face those issues squarely—get after them. Everything is hyper stressful and competitive at a level we never imagined when I was coming up. It’s an increasing problem in the world we live in. To early career scientists, I’d say take time for yourself. Take care of yourself first because you’re not good to anyone else if you don’t. That doesn’t mean six weeks of vacation every year, but it does mean taking care of yourself day-to-day.

Something else I tell early career folks is, “Don’t psych yourself out.” Don’t sit there and think of all the reasons it might not work. People sometimes think, “Oh, I want to go into science, but there’s so many reasons it might not work.” It’s important to understand that that’s just the reality of being in your 20s and starting a career. Everything else you could do might come with the same stresses, and there’s no way to predict what’s going to happen when you’re starting your career. When you understand that, it can help you. It might not make it easier, but it may be more comfortable to realize that career uncertainty is not unique to science.

TAGC aims to foster collaboration between communities and disciplines. Can you give an example of a collaboration that really helped your work?

Absolutely. I’ve been collaborative my whole life because I find it easier to work with other people. We have several collaborations with human geneticists. Sequencing is so fast now that the number of disease alleles is skyrocketing, but the number of alleles we know to be causative is not keeping pace. We have a lot of collaborations where human geneticists approached us with novel genes and alleles with unknown functions, and we explore them in model animals.

The biggest collaboration I’ve had has lasted over 12 years with a systems biologist in my department. He has expertise in computational biology, proteomics, and genomics. He thinks on a systems biology level, while I’m a classical genetic mechanism guy. We see the world in completely different ways, and our collaboration has forced me to question the basic assumptions of the field. I have had to explain why my questions are even interesting to someone who is extremely smart but isn’t steeped in the dogma of the field. I think the best collaborations push you out of your comfort zone.

Select Publications from the Wallingford Lab

The 200-year effort to see the embryo
Wallingford JB
Science. 2019 Aug 23;365(6455):758-759. doi: 10.1126/science.aaw7565

We Are All Developmental Biologists
Wallingford JB
Dev Cell. 2019 Jul 22;50(2):132-137. doi: 10.1016/j.devcel.2019.07.006

PCP-dependent transcellular regulation of actomyosin oscillation facilitates convergent extension of vertebrate tissue
Shindo A, Inoue Y, Kinoshita M, Wallingford JB
Dev Biol. 2019 Feb 15;446(2):159-167. doi: 10.1016/j.ydbio.2018.12.017. Epub 2018 Dec 21

A liquid-like organelle at the root of motile ciliopathy
Huizar RL, Lee C, Boulgakov AA, Horani A, Tu F, Marcotte EM, Brody SL, Wallingford JB
Elife. 2018 Dec 18;7. pii: e38497. doi: 10.7554/eLife.38497

Coming to Consensus: A Unifying Model Emerges for Convergent Extension
Huebner RJ, Wallingford JB
Dev Cell. 2018 Aug 20;46(4):389-396. doi: 10.1016/j.devcel.2018.08.003

Get to know the TAGC 2020 Keynote Speakers through our interview series.

Ed Buckler

Edward S. Buckler is a Research Geneticist with the USDA-ARS and an Adjunct Professor of Plant Breeding and Genetics at Cornell University. He began his career studying molecular evolution and archaeology, which got him interested in using natural diversity to improve crops and increase sustainability. Buckler developed association mapping approaches and germplasm to pinpoint genes and find natural variation controlling many maize traits. His group has also developed a wide range of big data, bioinformatic, and molecular tools that have been used to characterize and tap diversity in over 2,000 species. Currently, his group is developing approaches to use multiple sources of biological knowledge to design sustainable, energy-efficient crops that are adapted to numerous environments. Buckler has many leadership positions within the crop and genetics communities and is a member of the National Academy of Sciences.

What research are you most excited about right now, and why?

I’m most excited about the ability to use machine learning approaches on very fundamental molecular biology data. We’re starting to be able to model transcription and translation and to take those models and start applying them to a wide variety of species and crops. We have the opportunity to take detailed data about how molecular biology and biochemistry work and to apply it very quickly to crops in the field, to conservation biology problems, and to many other areas.

What do you like about working with crops? 

I think some of the biggest challenges facing the globe today have to do with how we interact with the environment—whether that’s climate change or how we produce our food. Crops provide us an opportunity to use advances in genetics to address some of these societal and environmental goals. We get to do really cool genetics and then see the application very quickly, whether that’s feeding people in the developing world or thinking about how we can sequester carbon.

Is there anything about yourself or the field that made you feel like you didn’t belong in science? What would you say to early career scientists struggling with the same feeling?

Personally, I was always encouraged to go into science. But my work has taught me that we need diversity of experience in science. The range of expertise we need to make real progress in solving questions about how we produce food systems is very wide. We need to work in diverse teams to think all the way through the implications of our research and to start asking the right questions about how to apply genetics. The only way we get the diversity of ideas we need is by having a diversity of people, which allows us to even think of the right questions to ask. So I would say to anyone who isn’t sure they fit in science: we need you, your individual experiences, and your unique viewpoint.

TAGC aims to foster collaboration between communities and disciplines. Can you give an example of a collaboration that really helped your work?

One of the first and earliest collaborations started because a colleague of mine raised the question: “Is there a way we could identify genes controlling provitamin A content in maize?” At the time, association mapping was just starting to look like it would work, so I said, “Yeah, I  think we can do that.” In a very short period of time, we were able to identify a few of the key genes and genetic variants that were responsible for provitamin A content, allowing breeders to quickly select for a 20- to 30-fold increase. Following that initial scientific discovery, it took coordinated teams of people working across East Africa and Mexico to get the technology deployed. The basic discovery only took a short time, but it took another five to seven years to see the effects of that discovery out in the field. It really does take working together to make the transition from basic to applied science happen.

Select Publications from the Buckler Lab

A unified mixed-model method for association mapping that accounts for multiple levels of relatedness
Yu J, Pressoir G, Briggs WH, Bi IV, Yamasaki M, Doebley JF, McMullen MD, Gaut BS, Holland JB, Kresovich S, Buckler ES
Nature Genetics. 2006 Feb;38(2):203-8. doi: 10.1038/ng1702

A robust, simple genotyping-by-sequencing (GBS) approach for high diversity species
Elshire RJ, Glaubitz JC, Sun Q, Poland JA, Kawamoto K, Buckler ES, Mitchell SE
PLoS One. 2011 May 4;6(5):e19379. doi: 10.1371/journal.pone.0019379

A study of allelic diversity underlying flowering-time adaptation in maize landraces
Romero-Navarro JA, Willcox M, Burgueño  J, Romay MC, Swarts KL, Trachsel S, Preciado E, Terron A, Delgado HV, Vidal V, Ortega A, Ortiz-Monasterio I, Vincente FS, Atlin G, Wenzl P, Hearne S, Buckler ES
Nature Genetics. 2017 Mar;49(3):476-480. doi: 10.1038/ng.3784

Dysregulation of expression correlates with rare-allele burden and fitness loss in maize
Kremling KA, Chen SY, Su MH, Lepak NK, Romay MC, Swarts KL, Lu F, Lorant A, Bradbury PJ, Buckler ES
Nature. 2018 Mar 22;555(7697):520-523. doi: 10.1038/nature25966

Evolutionarily informed deep learning methods for predicting relative transcript abundance from DNA sequence
Washburn JD, Mejia-Guerra MK, Ramstein G, Kremling KA, Valluru R, Buckler ES, Wang H
PNAS. 2019 Mar 19;116(12):5542-5549. doi: 10.1073/pnas.1814551116.

Get to know the TAGC 2020 Keynote Speakers through our interview series.

Sally Otto

Sarah (Sally) Otto is known for her theoretical studies of how biological systems evolve. Otto investigates the selective forces acting on genetic systems (recombination, ploidy level, gene duplications) and mating systems (sexual vs asexual reproduction, sexual selection, floral reproductive strategies). Complementing this approach, Otto’s group tracks yeast as they evolve to test evolutionary theories. Otto helped found the Canadian Society of Ecology and Evolution and has served as President of the Society for the Study of Evolution, among other Councils and Editorial Boards. Awards include a MacArthur Fellowship, a Guggenheim Fellowship, and the Sewall Wright Award.

What research are you most excited about right now, and why?

The most exciting shift in the field has been the ability to open the black box of evolutionary change—being able to identify the base pairs that underlie the response to selection and to connect the molecular information all the way up to evolutionary change. That was not even imaginable when I started in the field, and it’s been amazing to see.

My lab has been working on understanding how organisms are shaped not just through changes they experience in the diploid phase, but also what happens when they’re haploids. Gametes are haploids, and all sexual organisms spend time in the haploid phase; how important is that period to selection? We’re trying to figure out how evolution is shaped by what helps sperm and egg survive and thrive—not just what helps the organism survive.

What do you like about working with yeast?

It goes back to opening up that black box. We can expose yeast to new environments, see who survives, and sequence to figure out how they survived. Normally in evolutionary biology, you start with an organism, and you phenotype to understand what traits are present and how they’re evolving, and eventually you get to genes. With yeast, it’s almost the reverse. We use the genes to understand the phenotype because there’s often not a very clear visible change to help us understand how its evolving.

I started working with yeast because you can easily manipulate ploidy, how much sex they have, and when they have it. Even though they’re a classic “model” organism, yeast are surprising. They’re less likely to do what we expect them to do than you would imagine, and as a theoretician, I love that; it makes us throw out assumptions and suggest new hypotheses and new models.

What advice do you have for early career scientists?

From the very beginning, I felt that it was important to balance my life—to continue doing sports and reading and spending time with friends and family and so on. I knew I needed to keep a balance of activities to be happy. For me, that balance was key to being a successful scientist, allowing my brain to relax and explore creatively. Something that helps me is to imagine myself in old age reflecting back on my life: what would I be disappointed about missing in life? Then I make sure to add that into the mix! I strive for balance and encourage it in my students. 

TAGC aims to foster collaboration between communities and disciplines. Can you give an example of a collaboration that really helped your work?

There are so many! The work that I do is at the boundary between biology, math, and computer science, so I have always collaborated across disciplines and had students from different fields. The different skills and perspectives allow us to work on problems that we couldn’t tackle using only one approach. Math allows us to explore the intricacies of biology and to correct errors in logic, while biological experiments show us which assumptions need to be relaxed and reveal brand new phenomena. This intertwining of math and biology is what brought me to the field and continues to fascinate me. 

Select Publications from the Otto Lab

Theory in service of narratives in evolution and ecology
Otto SP, Rosales A
Am Nat. 2019. [In press]

Somatic mutations substantially increase the per-generation mutation rate in the conifer Picea sitchensis
Hanlon VCT, Otto SP, Aitken SN
Evol Lett. 2019 Jun 10;3(4):348-358. doi: 10.1002/evl3.121

Adaptation, speciation and extinction in the Anthropocene
Otto SP
Proc Biol Sci. 2018 Nov 14;285(1891). doi: 10.1098/rspb.2018.2047

Haploid selection, sex ratio bias, and transitions between sex-determining systems
Scott MF, Osmond MM, Otto SP
PLoS Biol. 2018 Jun 25;16(6):e2005609. doi: 10.1371/journal.pbio.2005609

The genome-wide rate and spectrum of spontaneous mutations differ between haploid and diploid yeast
Sharp NP, Sandell L, James CG, Otto SP
Proc Natl Acad Sci U S A. 2018 May 29;115(22):E5046-E5055. doi: 10.1073/pnas.1801040115

Get to know the TAGC 2020 Keynote Speakers through our interview series.

Alex Schier

Alex Schier obtained his PhD in Walter Gehring’s lab at the Biozentrum Basel. He spent his postdoc in Wolfgang Driever’s lab at Harvard, where he screened for and characterized mutants affecting zebrafish development. He started his lab in 1996 at the Skirball Institute of NYU School of Medicine and joined Harvard University in 2005. In 2019, he returned to the Biozentrum Basel. His lab has contributed to the understanding of the molecular basis of vertebrate embryogenesis and behavior and to the development of zebrafish as a model system. Schier has received NIH MERIT and PIONEER awards and was elected to EMBO.

What research are you most excited about right now, and why?

The whole field of building trees for development is pretty exciting. We are now building trajectory trees with single-cell sequencing; we can reconstruct the molecular trajectory a cell goes through as it differentiates. We can also build lineage trees that reconstruct the ancestral relationship between cells. There are still many challenges to building these trees. The technical challenge is to make them accurate, deep, and complete. Biologically, the challenge is figuring out what we’re actually going to learn from them. Still, there is a feeling of a new era that should hopefully provide exciting insights in the future.

It’s also exciting that single-cell approaches let us capture and define cell types at a level we couldn’t achieve before. We can identify new cell types and compare cell types between organisms. We can try to reconstruct the evolutionary history of cell type diversification. We can reconstruct the molecular trajectory of a cell during differentiation, letting us understand at the whole genome level how cells acquire specific structures and functions. The whole field is very exciting. At the moment, it’s largely technology and phenomenology, but I’m optimistic that some exciting biology will come out of this.

What do you like about working with zebrafish?

In a nutshell: transparent mutants. That’s the real power of the fish: they’re visually accessible. You can really see everything at the cellular and subcellular level, allowing you to do amazingly deep phenotyping on everything from brain activity to neuronal connections to cell migration to nuclear morphology and more. And with transgenic technologies and CRISPR, it’s easy to manipulate the genome. The road from genotype to phenotype is very short, and now genotype and phenotype changes can be made and detected at a very fine scale.

Is there anything about yourself or the field that made you feel like you didn’t belong in science? What would you say to early career scientists struggling with the same feeling?

I have always felt at home in science: thinking about science and how to approach the world as a scientist felt natural. However, there were definitely instances when I was not sure if I felt at home in the scientific community. 

For example, I was an intern at a big pharma company in college, and I remember being disappointed that people did science but didn’t seem to have passion behind what they were doing. It seemed more like a job than a calling, which didn’t seem much fun. That’s not generally true—there are lots of passionate scientists in biotech/pharma—but that summer, I wasn’t sure that this community was for me. Maybe that’s why I stayed in academia.

As a grad student, I once spoke to a very famous developmental biologist at a conference. As soon as he saw someone more important than me, he ended our conversation and walked away. It was rude, of course, but more than that, it felt like only the opinions of famous people counted.

I would tell early career scientists: find your niche and find your support network. There will always be people who think like you and love science and went through similar struggles to become a scientist, so I think there will always be people to offer support.

Science is still one of the most meritocratic professions. It’s not perfect—there are biases—but creativity and rigor go a very long way in science, no matter your background. If you’re creative and rigorous, do beautiful experiments, work hard, and create new knowledge, people will respect you. That’s something I like about science compared to other professions.

TAGC aims to foster collaboration between communities and disciplines. Can you give an example of a collaboration that really helped your work?

I have been super lucky to have had many generous and fun collaborators throughout my career. I did a big genetic screen as a postdoc, and it was only possible through collaboration. No single person could’ve done it. It took a large group, sharing ideas, doing it together. It was magical. 

As a starting PI, I had a wonderful collaboration with Will Talbot. We really fed off each other studying early zebrafish embryogenesis. When I moved to Harvard, I started working with Florian Engert and moved more into neurobiology. We came from very different fields and had very different personalities, and many things have happened between the two labs that couldn’t have happened individually. We’ve been trying to get at the connection of behavior to neural activity, of behavior to genetics.

More recently, on our genomics work, we’ve collaborated with Aviv Regev and Jay Shendure. This has really been the perfect combination of people with different backgrounds working together, creating more than the sum of their parts. Collaborations make research both better and more fun.

Select Publications from the Schier Lab

Phenotypic landscape of schizophrenia-associated genes defines candidates and their shared functions
Thyme SB, Pieper LM, Li EH, Pandey S, Wang Y, Morris NS, Sha C, Choi JW, Herrera KJ, Soucy ER, Zimmerman S, Randlett O, Greenwood J, McCarroll SA, Schier AF
Cell. 2019 Apr 4;177(2):478-491.e20. doi: 10.1016/j.cell.2019.01.048

Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis
Farrell JA, Wang Y, Riesenfeld S, Shekhar K, Regev A, Schier AF
Science. 2018 Jun 1;360(6392). doi: 10.1126/science.aar3131

Simultaneous single-cell profiling of lineages and cell types in the vertebrate brain by scGESTALT
Raj B, Wagner DE, McKenna A, Pandey S, Klein AM, Shendure J, Gagnon JA, Schier AF
Nature Biotechnology. 2018 Jun;36(5):442-450. doi: 10.1038/nbt.4103

Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm
Montague TG. Schier AF
eLife. 2017 Nov 15;6. doi: 10.7554/eLife.28183

Nodal patterning without Lefty inhibitory feedback is functional but fragile
Rogers KW, Lord ND, Gagnon JA, Pauli A, Zimmerman S, Aksel DC, Reyon D, Tsai SQ, Joung JK, Schier AF
eLife. 2017 Dec 7;6. doi: 10.7554/eLife.28785

Get to know the TAGC 2020 Keynote Speakers through our interview series.

Caroline Dean

Caroline Dean has been a project leader at the John Innes Centre Norwich since 1988. Her work on seasonal timing mechanisms in plants has led into a detailed mechanistic analysis of the regulation of the floral repressor FLC in Arabidopsis. FLC transcription is quantitatively modulated by an antisense-mediated chromatin mechanism that coordinately influences transcription initiation and elongation. The gene is also epigenetically silenced through a cold-induced, cis-based, Polycomb switching mechanism. FLC has therefore turned out to be an excellent system to dissect conserved mechanisms by which non-coding transcription and chromatin mechanisms regulate gene expression.

What research are you most excited about right now, and why?

I have always been fascinated by how plants flower so synchronously in spring. Plants need to integrate fluctuating temperature signals over many months and not get confused by a short period of cold in autumn. As soon as I had my own lab, I decided that that was what I was going to investigate.

The sensing and remembering of long-term temperature exposure is a process known as vernalization. I am particularly excited about our mechanistic studies aimed at understanding the molecular events behind the cold-induced silencing and epigenetic switching of an Arabidopsis gene called FLC, which is central to the vernalization process. It’s exciting that we now have the tools in Arabidopsis to dissect mechanisms that are central to seasonal timing in plants but also informative for basic epigenetic switching.

What do you like about working with Arabidopsis?

The scale of the community is amazing. I love the fact that there is so much available information and so many resources. Everyone is tackling different questions, and then serendipity comes along and connects the traits.

Is there anything about yourself or the field that made you feel like you didn’t belong in science? What would you say to early career scientists struggling with the same feeling?

For me, it was classic imposter syndrome. When you’re young, you think “This doesn’t make sense, but it’s what everyone else thinks, so I must be wrong.” I was always thinking that we must have gotten something wrong when we concluded something different to what was expected in the field. People assume that feeling goes away, but it doesn’t really. To early career scientists: always have confidence in your own assessment, and always ask the question—even if it might feel silly in your head. There will always be doubts and questions; my advice is to not let them overwhelm you.

TAGC aims to foster collaboration between communities and disciplines. Can you give an example of a collaboration that really helped your work?

After we’d done 20 years of genetics and uncovered a lot of molecular details, the molecular information became quite hard to put into a full picture. Many molecular mechanisms involve feedbacks and redundancies that make them very non-intuitive. We started to work with a theoretical biologist—Martin Howard—and that has made us stand back and put a framework together based purely on theory. We use theory to make hypotheses to test and then refine then theory, so the cycle of theory and experiment has helped us pick apart molecular mechanisms.

Select Publications from the Dean Lab

Distinct phases of Polycomb silencing to hold epigenetic memory of cold in Arabidopsis
Yang H, Berry S, Olsson TSG, Hartley M, Howard M, Dean C
Science. 2017 Sep 15;357(6356):1142-1145. doi: 10.1126/science.aan1121

Local chromatin environment of a Polycomb target gene instructs its own epigenetic inheritance
Berry S, Hartley M, Olsson TS, Dean C, Howard M
Elife. 2015 May 8; 4. doi: 10.7554/eLife.07205

Arabidopsis FLL2 promotes liquid-liquid phase separation of polyadenylation complexes
Fang X, Wang L, Ishikawa R, Li Y, Fiedler M, Liu F, Calder G, Rowan B, Weigel D, Li P, Dean C
Nature. 2019 May;569(7755):265-269. doi: 10.1038/s41586-019-1165-8

R-loop stabilization represses antisense transcription at the Arabidopsis FLC locus
Sun Q, Csorba T, Skourti-Stathaki K, Proudfoot NJ, Dean C
Science. 2013 May 3;340(6132):619-21. doi: 10.1126/science.1234848

Mutually exclusive sense-antisense transcription at FLC facilitates environmentally induced gene repression
Rosa S, Duncan S, Dean C
Nat Commun. 2016 Oct 7;7:13031. doi: 10.1038/ncomms13031