Students, postdocs, academic faculty, and industry researchers will all find benefits at the new Industry Sessions at TAGC, to be held April 22–26 2020 in the Washington DC region.

When industry scientists and academic labs collaborate, both society and science benefit.

That’s one of two big-picture messages Kailene Simon hopes will be conveyed through a new series of sessions to be held at The Allied Genetics Conference (TAGC) in 2020. The other? “You can do exciting, creative science in an industry setting!” says Simon, a senior scientist with the Rare and Neurologic Diseases Group at Sanofi.

Simon is working closely on developing the Industry Sessions with Mark Johnston, who is a professor at the University of Colorado School of Medicine and the Editor in Chief of GENETICS.

The sessions were originally proposed to meet the needs of GSA’s early career members. “Students and postdocs keep telling us they are interested in careers in industry but don’t know where to start,” says Johnston. “We wanted to help remove some of the mystery.”

But although there is a strong career element to the initiative (there is a recruitment event and an industry career session) the overall focus is on the science. At the “The Biotech Pipeline,” scientists will present on research that has moved from an academic setting to eventual clinical translation. In “Genetic Technology in Agriculture,” researchers will discuss their work improving crops and livestock through genetics. “There have been terrific advances in these areas in recent years that we think attendees will enjoy learning about,” says Johnston. At the Careers in Industry session, Simon will present on transitioning to a biotech career and will interview a range of industry scientists about their experiences.

Both Simon and Johnston hope the sessions will seed industry-academia collaborations.

“We can’t do our job without academic science,” says Simon. “Everything we do is built on the foundation of basic science.” Although industry labs typically have plenty of resources, she says, they don’t often have the luxury of time to explore new research avenues. That’s why industry researchers attend conferences like TAGC, where there are so many new ideas hatching and where they can build relationships with researchers working at the limits of the field. They also get to meet and recruit talented early career researchers into their labs.

The exchange is not one-sided. Academic researchers who spend their careers chasing down new ideas and projects lack the infrastructure to see their ideas applied in the clinic or marketplace. It is quite common, says Simon, for academic labs to receive funds from industry labs, thus establishing a collaboration with the common goal of clinical application. This allows the academic lab to “keep doing what they’re doing,” i.e. pursuing discovery research and building knowledge. Collaborating with industry can provide academic labs with not only funds, but translational expertise, access to clinical or field samples, and the institutional machinery for bringing an idea through development and approval to market.

“Genetics has so much potential for clinical application, I think it’s important that the translational side is also part of the discussion,” says Simon. Like many in the GSA community, she has a particular interest in rare diseases. Gene therapy is the only true cure for many of these diseases, she says.

“If we are to stand a chance of being successful, we’ll need all hands on deck.”

Learn more about the Industry Sessions at TAGC ≫

Learn more about ways to connect with potential colleagues and employers at TAGC ≫

The recipient of the 2018 Crow Award reveals details of flu evolution at the smallest —and largest—scales.

For many viral diseases, a vaccine can provide lifelong protection. But for flu, you need a new shot every year. The influenza virus evolves so fast it presents a constantly moving target for both our immune systems and public health authorities, fueling epidemics like the particularly bad season we just endured. With over 30,000 people hospitalized in the United States alone this season, the flu provides a dramatic reminder of the importance of understanding evolutionary dynamics.

Katherine Xue, a graduate student at the University of Washington, is revealing the mechanics of influenza evolution on scales ranging from an individual person up to the entire planet. Xue was awarded the 2018 James F. Crow Award for Early Career Researchers for her doctoral work on the subject after a presentation at the Population, Evolutionary, and Quantitative Genetics Conference in May.

In a special session of talks by Crow Award finalists, Xue spoke about using deep sequencing to examine diversity in flu virus populations.

“Up until recently, we were only able to look at the average genetic identity across the millions or billions of flu viruses in a single infection,” says Xue. “We’ve used deep sequencing to show that within a single infection there are fast evolutionary dynamics that have been invisible to previous technologies.”

Xue approaches clinical topics with the conceptual tools developed by evolutionary and population geneticists. Linking ideas across fields is characteristic of Xue, says her mentor Jesse Bloom (Fred Hutchinson Cancer Research Center / University of Washington), whether it’s between medicine and evolutionary theory or between science and the humanities.

“What makes Katherine stand out is her ability to think about big scientific concepts and connect ideas,” says Bloom. “She’ll see and connect ideas in ways that I can’t.”

Viral cooperation

When Xue first rotated in Bloom’s lab, she was working on a molecular virology project about how a particular viral protein binds to a cell. In the course of examining sequence databases, she noticed the mutation she was studying was often ambiguously annotated.

Inspired by this hint of population diversity, she wondered whether the two viral variants might interact with each other. She was able to establish that the mutation tended to occur alongside the wild type version within a population; the mutation was deleterious to virus reproduction on its own but beneficial when mixed with wild-type. This example of cooperation suggests that interactions between different variants within flu populations can be important factors in virus evolution.

A glimpse of evolution in action

But can evolution be detected within the virus population of a single individual? Xue was drawn to the question of how global flu evolution traces back to the founding infections in which each mutation must first arise.

“I was intrigued because it was hard to imagine how this works,” says Xue. “Flu infections are very short; there’s not a lot of time for a new mutation to reach frequencies large enough to ensure it makes it over to the next infected person.” In the language of population geneticists, flu populations are repeatedly subjected to extreme bottlenecks. But observing such rapid evolution in action is extremely challenging.

Xue and her colleagues in the Bloom lab used a unique approach to get around this problem. They partnered with clinicians Michael Boeckh and Steve Pergam at the Fred Hutchinson Cancer Research Center, who had collected samples from four immunocompromised patients over the course of their months-long flu infections. Deep sequencing these samples gave them an in-depth view of a process that would normally be finished within days in a person with healthy immune defenses.

“I initially had doubts that this project would show us anything interesting or be worth doing,” says Bloom. “But Katherine is very independent and persistent, and she kept going despite my occasional words of discouragement.”

The results were dramatic. Over the span of about two months, there was a substantial amount of flu evolution within each patient. Mutations arose regularly, fluctuated in frequency, and even became fixed in the population in a few cases. They also saw evidence that some of these changes are due to selection. The same mutations would often arise independently and then rise to substantial frequencies in multiple patients, suggesting these particular changes were adaptive.

Remarkably, the mutations that arose repeatedly in different patients were sometimes the same mutations that spread through the global flu population within the next decade. The immunocompromised patients seemed to be microcosms of global evolutionary patterns. “We were astonished,” said Xue.

Most of these recurring mutations affect the part of the flu haemagglutinin protein that is most recognized by the host immune system, so the team hypothesizes that the changes help the flu escape host defenses.

These results raise many questions about how evolutionary dynamics interact across scales. How far do the conclusions generalize? Where and when do natural selection and genetic drift act? How do normal week-long infections generate enough diversity to fuel rapid global evolution? Could understanding these processes translate to better flu season predictions? Xue’s graduate research continues to explore flu evolution with these questions in mind.

Connecting ideas

The scientific big picture is never far from Xue’s mind, it seems. Alongside her thesis research, Xue is pursuing a certificate in science and technology studies, with a capstone project on the history of flu research. “I have really loved being part of the history, philosophy, and sociology of science community here,” she says. “It’s given me a lot of perspective that has been really enriching.”

A few years ago Xue helped start the UW Genomics Salon, which is a group of students and postdocs who take part in freeform discussions about the intersections of science and society. These discussions touch on policy, advocacy, communication, education, representation, law, art, and a host of other topics.

Bloom thinks Xue’s broad interests are yet another reflection of her creativity and ability to link ideas across fields. Before graduate school, she spent a few years working as a science writer for the Harvard Magazine. “She’s an exceptionally good science communicator and very dedicated to creating connections between science and other fields. It’s pretty awesome to have someone like that around!”

[youtube https://youtu.be/fTdaAwqdt0k&w=500&rel=0]

Watch #PEQG18 presentations from all the other  outstanding finalists for the Crow Award here.

Model organism researchers face shared challenges in communicating the value of their work. How do you get policymakers to fund research on a microscopic organism they’ve never heard of? How do you explain to the public why scientists spend time understanding yeast and frogs and flies?

In 2015, the ciliate research community decided to invest in a shared tool they could all use to help convey the importance of research on their model system. The result, a 6-minute “Why Ciliates?” video screened at The Allied Genetics Conference in 2016, helped introduce these fascinating organisms to participants from all the other communities attending the meeting. Inspired by the project, and the “Small Fly, Big Impact” Drosophila videos, many attendees expressed the desire to try a similar approach for their own model system.

https://vimeo.com/191812936

‘Why Ciliates?’ stars the one-celled wonders whose mini size belies their mega importance in basic research and drug development. Meet the passionate scientists, including Nobel laureate Carol Greider, as they advocate continued funding of basic research as the necessary precursor to the translational breakthroughs that will cure disease.

In advance of the Ciliate Molecular Biology Conference this July 17–22, 2018 in Washington, DC, we talked to the makers of “Why Ciliates?” to learn more about making a model organism video and how to overcome the challenges of a big communication project of this type.

Diana Ritter runs the video production company Flying Dreams Inc. Contact Diana on flydrms@gmail.com.

Ted Clark is Professor of Parasitology and Immunology at Cornell University

Jeff Kapler is Professor and Chair of the Department of Molecular and Cellular Medicine and Professor of Biochemistry & Biophysics at Texas A&M University

(Both Clark and Kapler are members of the Steering Committee of the Tetrahymena Genome Project)

What was the inspiration for the video?

Ted Clark: I had worked with Diana to make “Expedition: Science”,  a video for a laboratory course called ASSET we’ve developed to teach basic biology to high school students. After I showed the video at the “Ciliates in the Classroom” workshop at the Ciliate Molecular Biology Conference, some of the folks in the Tetrahymena community asked if we could do a similar video to pitch ciliates as model organisms to the broader scientific community and beyond.

Jeff Kapler: I’m on the Tetrahymena Board, and around this time we felt the funding environment was becoming increasingly difficult for those using model systems. We wanted a way to get the word out about the value of ciliates that could be shown to Members of Congress, NSF directors, NIH directors, the public. Something that could be used on our webpages, in grants, in the introduction to talks, at outreach events and so on. Ted and Diana had done a great job with the education video, so we were able to get the community really excited about it.

How did you fund the project?

Jeff Kapler: We developed the initial concept, and then we just asked for support via the ciliate e-mail listserv. People really got behind it. We got donations anywhere from $10 to $2000 coming from all over the world—old retirees came out of the woodwork to support it and even grad students making a pittance of a salary. It was like a GoFundMe without the overhead! We raised about $5000 that way, and the remaining $20,000 or so were provided by the Tetrahymena Stock Center.

What aspects of the video were most successful?

Ted Clark: Diana and I share a similar warped sense of humor—we knew we could rely on humor to make it more approachable in contrast to the more dry, informational tone of some science videos.

We’ve found that people respond to it naturally, it’s very engaging. Part of that was we had to find the right people. Diana asked for interviewees who are passionate and can tell a good story, so I chose people who I knew would make it exciting.

We also received a lot of comments on the representation of women in the video.

Diana Ritter: That was not an accident! Something that really struck me and engaged me when my kid was in kindergarten about 15 years ago, was that when the kids were asked what they wanted to be when they grew up, all the boys said things like fireman and astronaut and doctor, and to a person all the girls said ‘I want to be a mommy’. Now I love being a mommy, but that put fuel on my fire to show more women and girls doing science.

Jeff Kapler: The other thing that stood out when I saw the video was the young people in it—it wasn’t just a bunch of old men.

How do you prepare for production?

Diana Ritter: You have to start by identifying what you want to accomplish, your message, and your audience. That helps you think about the style; do you want it to be rapid-fire and provocative?  Or attention-getting with a more laid back, conversational, or news report approach?

You need to keep your budget in mind when you are planning, because this will guide lots of decisions about resources. If you have a very limited budget you will need to be as efficient as possible. You might be able to use some existing footage and graphics for example, and consolidate all the interviews at an event, use local crews etc.

People often think you need a script in advance, and will ask people to memorize lines. That’s tough to pull off. My approach is to reverse engineer the script. We know the messages we want, so I come up with interview questions that elicit that content  in people’s responses. It can make the editing trickier, but we feel it results in a more natural and conversational end product.

Diana, how did you incorporate feedback from the scientists in the finished product?

Diana Ritter: I worked closely with Ted. After the interviews, we sent notes on our selects to Ted along with  a rough edit. He reviewed the scientific information and made suggestions, then we would make changes and continue the conversation through several more edits. It was a good give and take, because he knows the science while we know the pacing and style.

How long did the project take?

Diana Ritter: After the budget was finalized, there were maybe two weeks of scheduling people, assembling a crew, securing locations and agreeing on a general outline of what we hoped to get. We had a three-day shoot. Reviewing the material took several days, the back and forth of fact checking and rough cuts took a couple of weeks. And then another week to arrive at a final edit. So about a month to six weeks.

What were the biggest challenges?

Diana Ritter: One of the big uncertainties was getting the right lineup to adequately represent the ciliate community. We wanted to include some heavy-hitters and Nobelists who always have very busy schedules. We were lucky to be able to shoot around a conference in Washington, DC, where we knew we could get three of the interviews and then stop in Maryland to talk to Carol Greider and Sean Taverna on the way back, and then do another day in Boston.

From a creative standpoint, the challenges were like any communication project: how do you take the vast amount of material and find the order and flow—while keeping your audience engaged? The project was really a pleasure—all the people we spoke to were very happy to participate and share with us their time and enthusiasm!

GSA is currently accepting proposals from students and postdocs for the next round of Career Development Symposia. Gain leadership experience and serve the early career scientist community!

Many postdocs feel powerless. But early career researchers can work together to take control of their future, says Sarah Dykstra, a postdoc at Tufts University and co-organizer of the Boston Symposium on Careers and Collaboration in Science (B-SOCCS). To support this process, the Boston Postdoctoral Association (BPDA) developed a career symposium designed to enhance postdocs’ formal training and to forge new connections between early career scientists.

This successful event got its start with funding through GSA’s Career Development Symposia program, but from this early seed the BPDA were able to grow their financial support by ten-fold—and scale up their event to match their big goals.  

“It was critical that GSA was so willing to put their faith in us,” says Dykstra. “Many people didn’t initially have a lot of confidence that a group of postdocs could organize a new event of this scale. GSA’s funding gave us the credibility to approach other groups for both sponsorship and partnerships.”

Drug discovery workshop led by NIBR researchers. Pictured is Alokesh Duttaroy.

The Boston Postdoctoral Association is a coalition representing postdocs from 17 academic and industry research institutions in the Boston area. It was established in 2013 to support postdoc professional development and advocacy needs.

In its first years, the group began by organizing small events and programs. But as they became more established and organized, Dykstra challenged the BPDA to develop a much larger career symposium. They decided such an event could bring their community together to foster collaboration between researchers in both academia and industry. They also wanted to empower postdocs with practical tools for enhancing their professional development.

“We were trying to fill the gaps we felt were missing in our own training,” says Dykstra. 

With this idea, they applied for and received $2000 funding from the GSA, as part of its program to support student and postdoc members organizing career and professional development symposia to early career scientists. Using that vital confidence boost and the help of another early supporter—Angela Florentino, the Broad Institute’s Program Manager for Academic Affairs—they secured space for the meeting and reached out to a wide range of groups for sponsorships and partnerships. They also received early guidance and support from personnel at the Novartis Institutes for Biomedical Research (NIBR), including the head of the NIBR postdoctoral program, Leslie Pond and several senior scientists and program directors.

To help share the workload, the event was organized through the teamwork of nearly 60 postdocs. They also tapped into the expertise of their network by seeking advice from successful event organizers and fundraisers.  

These experiences proved valuable for the organizers’ own career skills and networks. Dykstra is enthusiastic about the boost she gained from being involved, including better project management, more confidence, experience working in large teams, managing direct reports, dealing with people across different sectors, and learning about a wide range of topics that she had never been exposed to before.  

The end result was a busy 1.5-day event attended by around 350 people, with a mix of workshops, panels, networking events, scientific talks, and posters. The sessions were designed to draw early career researchers focused on academic careers, those focused on industry, and those who were undecided, bringing them to together to cross-pollinate their ideas. 

To give attendees a primer for the networking event on the first night, B-SOCCS kicked off with a talk on scientific networking from Daniel Jay, now the Dean of Tufts University’s Sackler School of Graduate Biomedical Sciences. Then came the real thing. “We packed the first floor of the Broad Institute with posters and people and food and encouraged everyone to mingle,” says Dykstra. “We couldn’t get them to go home!” 

The following day included three concurrent sessions in three general tracks: academic topics like grant writing and academic interviews, industry topics like entrepreneurship and drug discovery, and crossover topics such as communication and leadership. There were also scientific sessions and posters, with prizes.

Anchoring all this professional development and networking were two inspiring presentations. Jay Bradner, President of NIBR gave the keynote on the first night. Bradner helped pioneer the open science movement in biology, experimenting with an “open source” approach to the normally secretive world of drug discovery. The plenary talk was given by Phil Sharp, Nobel-winning co-discoverer of RNA splicing, who spoke on the history and future of biotech in the region.

When asked if she has any advice for students and postdocs thinking of organizing their own career symposia, Dykstra encourages them to apply for Career Development Symposia funds from GSA. “It would have been another year in the planning without that initial funding.”

She also emphasizes both building on the expertise of others and trusting your instincts.  

“You’re trained to analyze problems. If you think there’s a problem, acknowledge that it exists and be methodical about solving it.”  

The BPDA is already planning the next B-SOCCS, once more supported with GSA funding. This time they hope the GSA contribution will be used for travel awards to bring people to the symposium. They are also working on how to make the event even more useful to attendees. Dykstra is excited by some of the new proposals. “One of the things I learned from this experience was that although I have good ideas, together our team has great ideas.”

Applications for the next round of GSA’s Career Development Symposia are due January 10, 2017. Read these tips for a successful application first!

Richard Lewontin

The Thomas Hunt Morgan Medal is awarded to an individual member of the Genetics Society of America for lifetime achievement in the field of genetics. It recognizes the full body of work of an exceptional geneticist. The 2017 recipient is Richard C. Lewontin, whose contributions and influence have profoundly shaped the field of evolutionary genetics. As a testament to this legacy, his nomination for the Morgan Medal was co-signed by 160 faculty members from around the world.

A student of Theodosius Dobzhansky, Lewontin’s early work established the two-locus theory, which laid the foundation for our understanding of linkage disequilibrium. In the 1960s, he collaborated with biochemist Jack Hubby on a method to quantify natural genetic variation using protein gel electrophoresis. This approach helped launch the field of molecular evolution and spurred a great influx of data into a formerly theory-dominated domain. The subsequent contributions of Lewontin and his group helped set the stage for much of modern population genetics and genomics research.

As well as this direct impact, Lewontin influenced the field through his guidance and inspiration, as well as through his capacity to spur vigorous but productive debates. His prominent role as a writer and social commentator included highlighting problems with the inference of heritability, concepts of race, and the overemphasis of genetic influences on phenotypes.

This interview was published in the December 2017 issue of GENETICS.

What inspired you to become a scientist?

I had an inspiring high school biology teacher. He was a very charismatic person who had a suite of students who followed him around every day—both my wife and I were among them.

What drew you to studying evolutionary genetics?

To be honest, I don’t remember! I don’t think it was because the problems of evolution per se were more interesting to me than other biology problems. Most of the influences on my career came from particularly charismatic teachers. I was a student of Theodosius Dobzhansky, and he was a very inspiring professor, as was the geneticist Leslie Dunn, whose lab I worked in tending mice. I think that’s what it comes down to. They were people who impressed me greatly, and I followed their path.

What was it like to be a student of Dobzhansky’s?

One didn’t see a great deal of him because he spent a lot of time in Brazil and other places collecting flies. But when he was at Columbia, he sat every day at his microscope looking at fly chromosomes, and you would sit down next to him while he was peering down the microscope and have discussions with him about various questions you had. I think it was the possibility of having that intimate relationship with a powerful mentor that was very important to me. Also important to the experience was the general physical atmosphere: two or three of us would share a big room together and would have our own world with our libraries and our tables. Dobzhansky was often away, and we led a pretty independent life. I chose my own PhD thesis, I could argue with him and fight with him and tell him he was out of his mind. It was an environment in which graduate students felt free to do what they thought was best.

Many of today’s prominent evolutionary and population geneticists trace their “academic lineage” back to your lab. What do you think was special about your group? What advice would you give to other mentors?

The atmosphere was a group of interacting equals rather than a professor telling people what to do. I would never dream of assigning a thesis to a student, for example. I also happened to have had some experience in statistics so I was able to help students deal with theoretical problems as well as experimental ones.

The advice I would give is not to try to direct the work of your students and associates, but to encourage them to do their own thinking and to invent their own problems. I think giving students responsibility and freedom is important. It’s also desirable to have a good knowledge of mathematics and statistics. That kind of training was very helpful in my life. Though it isn’t necessary; Dobzhansky could barely add two and two!

What advice do you have for the readers of GENETICS?

Not to overemphasize the determining power of genes in either behavior or development. The basic truth about genetics is that organisms are the consequence of complex interactions between internal genetic factors and external influences. It’s only by observation and experiment that you can know how important each influence is. I would add that genotype and environment interactions are not complete as an explanation because there are also random developmental effects that are orthogonal to genotype and environment. It’s an oversimplification to say your behavior is a consequence of genotype and environment—that’s kind of vacuous! There’s a tremendous amount of behavior that is ununderstood (not misunderstood), things for which we have no satisfactory explanation. Why did I decide to become a geneticist? I don’t have the foggiest notion. There are a lot of random connections of neurons, and these give rise to patterns for which we try to invent explanations.

These attempts to find simplistic, formulaic explanations for phenotypes leave out of consideration random factors. I’ve done a lot of experiments, particularly as a student, that show that even when you control the environment and genotype of an organism that there’s still a lot of variation between replicated organisms all growing up in the same test tube. This is the result of random molecular events that occur in development. And when you talk about the central nervous system, since we really don’t understand it, we don’t know how important random connections of neurons are in determining our understanding, our attitudes, our behavior, our intelligence, anything. The central nervous systems is one of the great unsolved mysteries of biology. There’s so much we don’t have an explanation for in the development of our thoughts and attitudes and abilities. We may never have an explanation. You have to live with that; no matter how much you’re committed to science, there’s a hell of a lot no one will ever understand.

Jonathan Hodgkin

The Genetics Society of America’s Edward Novitski Prize recognizes a single experimental accomplishment or a body of work in which an exceptional level of creativity and intellectual ingenuity has been used to design and execute scientific experiments to solve a difficult problem in genetics.

The 2017 winner, Jonathan Hodgkin, used elegant genetic studies to unravel the sex determination pathway in Caenorhabditis elegans. He inferred the order of genes in the pathway and their modes of regulation using epistasis analyses, a powerful tool that was quickly adopted by other researchers. He expanded the number and use of informational suppressor mutants in C. elegans, which are able to act on many genes. He also introduced the use of collections of wild C. elegans to study naturally occurring genetic variation, paving the way for SNP mapping and QTL analysis, as well as studies of hybrid incompatibilities between worm species. His current work focuses on nematode-bacterial interactions and innate immunity.

This interview was published in the December 2017 issue of GENETICS.

What inspired you to become a scientist?

I was exposed to research from a very early age and learned a great deal from my father and grandfather. My father was Alan Hodgkin who was a physiologist and neurobiologist, and my mother’s father was Peyton Rous, who was a virologist who discovered the Rous sarcoma virus.  I had various other scientific relatives —cousins and what have you—going further back. I wouldn’t say it was inevitable that I became a scientist, but it was the easiest career option! And of course, I was inspired by the people who taught me at university, from about second-year onwards, who were enormously influential.

Why did you choose C. elegans as your research system?

Very largely because of Sydney Brenner. He gave a lecture that I heard as an undergraduate, and I thought that here was a great system for investigating the things in biology that I thought were really, really interesting. So, when I graduated I went and persuaded Brenner take me on, and he —somewhat reluctantly—did. He was inspirational and brilliant in all ways, truly extraordinary. And it was indeed a great system. It has gone off in all sorts of directions and keeps on generating new lines of research and new amazing discoveries.

What’s the most memorable moment from your career so far?

Probably when I realized the spectacular effect of a particular mutation on sex determination in C. elegans. It was a dominant mutation that caused the animal to change sex completely, and I’d previously found mutations in the same gene that caused the absolutely opposite transformation. It was just astonishing to realize that with that one gene you control everything about the animal’s sex.  This was a very satisfying and elegant result, which came together in a fairly short time.

Who have been your most important mentors?

At university, I was very lucky to be taught directly by a superb yeast geneticist, Brian Cox, whom I much admired. He did a lot of things that were underappreciated; for example, he discovered one of the systems that turned out to involve a yeast prion. He made it clear to me how immensely powerful genetics is. Then as a grad student, Sydney Brenner obviously, but also other people at the MRC Laboratory in Cambridge, like molecular biologist Mark Bretscher, who was very influential and full of good advice, and also inspirational people like Francis Crick. Francis was the only person smarter than Sydney at the MRC Lab!!

What types of questions are you fascinated by?

The big questions in development. Looking back on it now, I think what got me into research —and what I thought C. elegans was particularly powerful for—is a very difficult question that remains in many ways completely unanswered. How do you specify complicated behavior genetically? It’s obvious from all sorts of examples of instinctive behavior that they must be genetically programmed. How on earth do you do that? We have no idea whatsoever! We’ve made enormous progress in understanding development and the basis of the nervous system, but how do you do genetically specify things like the behavior of crows that can make tools out of bits of leaf? They don’t need to learn that! If you take a New Caledonian crow and allow it to hatch and grow up in isolation, after a while it will start finding bits of leaves and turning them into tools for picking up insects. I’m baffled by how such behavior can be generated, and I’d love to know the mechanism.  C. elegans has such simple behavior that we may   be able to eventually understand how it’s specified, though the more we more we learn about the worm, the fancier its behavior becomes. I don’t work in this area anymore, but the people who do are making nice progress. The most sophisticated aspects of it are still very mysterious though, and big questions remain unanswered.

What are you currently working on?

I’m working on how worms and bacteria interact with each other, and how the worms are able to fight off disease, how they recognize that they’ve got a disease, how infection happens, how some bacteria are able to infect some worms and not other worms. That involves a lot of interesting questions that still haven’t been answered, but it’s also led to lots of unexpected things along the way. For example, finding a bacterium that kills worms by causing them to stick together by their tails, but the worms can sometimes escape by dividing themselves in two. Nobody knew that nematodes s could do autotomy, so that was really surprising!

Autotomy raises questions about how they manage to do it. Unfortunately, so far, the half-worms survive but won’t regenerate. If you cut Planaria in half they will regenerate, but nematodes do not. Or at least we can’t get them to do it, which doesn’t necessarily mean it doesn’t happen.

If you hadn’t been a scientist, what would you have liked to have become?

Probably an archaeologist. I spent a lot of time hanging out with archaeologists on excavations until about the end of 1980s. Archaeology is like doing biological research in that you’re always discovering things, and it’s like genetics in that it’s open ended. The trouble with being an archeologist is there’s a factor of maybe 100 in the difference in employability between a biologist and an archaeologist.

What’s the best advice you ever received? 

Perhaps what Mark Bretscher said to me, which was: everything depends on having a good assay. I think that this is true whatever kind of experimental science you do, and it’s something I’ve always kept in mind. Avoid assays that are too arduous. Sometimes you have no choice, but if you can, try to get a stringent assay and one that’s easy to do.

What advice would you give to younger scientists?

Hang in there. It has gotten harder. It would be hard to deny, both in terms of career prospects and in terms of some of the questions that are out there, that it’s not as easy to do research as once it was.  But on the other hand, science goes on being enormously rewarding and enjoyable, and amongst other things there is a very strong community. You find yourself working with a lot of people who are interested in the same things and are all very bright, very funny, and very agreeable. That was the great thing about working at the Molecular Biology Laboratory in Cambridge: you instantly realized that it was a wonderful environment, nonhierarchical and dedicated and excited about research. Many other occupations can involve more or less going around in circles, or trying to solve incredibly difficult social problems. There aren’t many careers that go on being satisfying and fascinating in quite the same way as this one—or where you actually get to move back the frontiers of knowledge.

Susan A. Gerbi

The Genetics Society of America’s George W. Beadle Award honors individuals who have made outstanding contributions to the community of genetics researchers and who exemplify the qualities of its namesake. The 2017 recipient is Susan A. Gerbi, who has been a prominent leader and advocate for the scientific community.

In the course of her research on DNA replication, Gerbi helped develop the method of Replication Initiation Point (RIP) mapping to map replication origins to the nucleotide level, improving resolution by two orders of magnitude. RIP mapping also provides the basis for the now popular use of λ-exonuclease to enrich nascent DNA to map replication origins genome-wide. Gerbi’s second area of research on ribosomal RNA revealed a conserved core secondary structure, as well as conserved nucleotide elements (CNEs). Some CNEs are universally conserved, while other CNEs are conserved in all eukaryotes but not in archaea or bacteria, suggesting a eukaryotic function. Intriguingly the majority of the eukaryotic-specific CNEs line the tunnel of the large ribosomal subunit through which the nascent polypeptide exits.

Gerbi has promoted the fly Sciara coprophila as a model organism ever since she used its enormous polytene chromosomes to help develop the method of in situ hybridization during her PhD research in Joe Gall’s lab. The Gerbi lab maintains the Sciara International Stock Center and manages its future, actively spreading Sciara stocks to other labs. Gerbi has also served in many leadership roles, working on issues of science policy, women in science, scientific training, and career preparation.

An abridged version of this interview was published in the December 2017 issue of GENETICS.

How did you get involved with the March for Science?

As scientists, we can enjoy doing science because those of us fortunate enough to have research grants from the NIH and NSF receive them through tax dollars. So, we have an obligation to share with the public what our science is about. It’s important for scientists to learn how to speak to the public because the worst thing we can do is speak in such technical terms that their eyes will glaze over and they say, “this is why I didn’t want to study science in the first place!” Of course, this has always been true, but it seems especially true in the current era. There seems to be a disregard for science as a methodology. I was really spurred on by [GSA President] Lynn Cooley at the fly meeting, where she challenged me when she was presenting me with the Beadle Award. She mentioned that I had played a role in public policy through the American Society for Cell Biology [ASCB] and through FASEB [Federation of American Societies for Experimental Biology], as well as through the AAMC [American Association of Medical Colleges]. And then she said, “we need you now!”

I went home and I thought: yes, the field needs people to be actively involved in public policy at this particular time in history. So, with some difficulty, I found the local leaders for the March for Science in Rhode Island and then played an active role in mobilizing the Brown community. The underpinning of the March for Science was applauding the importance of science and the scientific approach. I enjoyed that experience and I really thank Lynn for her challenge to me, as well as her inspirational writings about how the community of geneticists really needs to be vocal.

Even though the March for Science itself was amazingly successful, it must go on beyond that. We need to speak to our congressional representatives, we need to speak to the general public, and to our neighbors about what we do, why it’s exciting, and why it’s important for advances in our society.

What inspired you to become a scientist?

Years ago, there was a study reported at the ASCB [American Society for Cell Biology] that found that many prominent women scientists have their fathers as their role model—that was certainly true for me. My father was a physician scientist. He grew up in Italy and went to medical school there, but he also was involved in renal hypertension research. During World War II he came to this country and was ultimately affiliated with Columbia University College of Physicians and Surgeons. When I was a youngster he would bring me to lectures at the New York Academy of Sciences, which was terribly exciting. I would be learning about things in high school biology and then would get to hear talks by the people making the discoveries. Holley spoke about the structure of tRNA, for example, and Palade about ribosomes, and Nirenberg about cracking the genetic code.

What drew you to studying chromosomes?

I became interested in chromosomes in high school after reading a Scientific American article by J. Herbert Taylor who had discovered that replication of chromosomes was semiconservative, which temporally paralleled the discovery by Matt Meselson at the DNA level. Then when I went to Barnard College I had the opportunity to take a molecular genetics course with Herb Taylor, and that confirmed my interest in chromosomes and replication. I knew I wanted to do a PhD on chromosomes, and one of the emerging leaders in the field at the time was Joe Gall. I was planning to apply to the University of Minnesota, where he was at the time, but I learned he was going to join the faculty at Yale, so I applied to Yale. The rest is history, as they say!

It was a fortuitous time to be in his lab because the method of molecular hybridization had just emerged from the work of Spiegelman, where radiative probes are hybridized to DNA captured on nitrocellulose filters. It was a no-brainer to try to expand that to the chromosome level. Joe Gall went to a meeting in South America where several scientists brainstormed about how they might best apply this method. They all went home to their labs and got hung up on the controls. But Gall, being a fabulous biologist, said he was going to use a system where he knew what the biological answer should be and then he would work things out from there.

He and my fellow grad student Mary-Lou Pardue worked out the initial method of in situ hybridization. They used the stage of meiosis in Xenopus oocytes where you find thousands of nucleoli, and everything in the field pointed to the fact they contained amplified genes for ribosomal RNA, and indeed that turned out to be the case. The next step was to apply the method to chromosomes themselves rather than amplified nucleoli, and I was part of that effort. We did the first in situ hybridization to chromosomes using the gigantic polytene chromosomes from the salivary glands of the lower dipteran Sciara, as well as Drosophila. Sciara polytene chromosomes are a bit larger than those of Drosophila because they have a few more rounds of endoduplication.

How did your interest in ribosomes begin?

The probe we used in the in situ hybridizations was ribosomal RNA labeled with tritiated uridine, and we used Xenopus rRNA because it was available from tissue culture cells. I wondered how Xenopus RNA could hybridize to fly chromosomes. I thought there must be some sequences that have been retained during evolution, and that started me on the long path of studying eukaryotic ribosomal RNA using evolution as a guide.

So, we reasoned that sequences with strong functional consequences should be evolutionarily conserved. We started with Xenopus rRNA because it was the first eukaryotic gene ever cloned. By hybridization we found there were regions of conservation even between bacteria and eukaryotes. Then we produced the first rRNA sequence from a metazoan. We modeled the secondary structure of rRNA using principles of compensatory base changes—where base-pairing in hairpin stem regions would be retained even if the sequence changes—and we found that there was a core structure that was conserved between Xenopus, yeast, and E. coli.

Our subsequent studies found that eukaryotic rRNA is larger because of insertions that were highly variable in sequence length and nature. We called them expansion segments, and initially people thought they were a remnant of evolution and didn’t have any function, but current studies by John Woolford making mutations in yeast and by other groups doing X-ray crystallography and cryo-electron microscopy are starting to zero in on whether they may indeed be playing functional roles.

There are now an enormous number of rRNA sequences that have become available across the three domains of life. We did a bioinformatic study and confirmed that there were some sequences that were universally conserved, and in addition we discovered a new category: sequences that are fully conserved within one domain of life, such as eukaryotes, but not present in that sequence composition in the other two domains. That points to the possibility that they carry out a domain-specific function. Intriguingly the majority of them line the tunnel of the large ribosomal subunit through which the nascent polypeptide exits. Whether it plays a regulatory role feeding back to the nearby peptidyl transferase center is something worthy of future study.

What can we learn from understanding Sciara re-replication?

DNA re-replication leading to gene amplification is a hallmark of many cancers, but the underlying mechanism isn’t fully understood. Whether re-replication is an alternate or a primary mechanism that subsequently leads to breakage and rejoining and recombination hasn’t been studied. One cannot induce amplification in cells in a way that allows you to study the initiating events; you only see the final outcomes of amplification. So, it became very desirable to look for model systems where this is a natural part of development.

There are two known cases of developmentally programmed locus-specific re-replication: Drosophila follicle cells, and salivary gland polytene chromosomes from the end of Sciara larval life. We want to understand how these origins of replication bypass normal cellular controls. Once we figure that out, this may serve as a paradigm to understand whether the same thing is happening in cancer cells.

What is the function of developmentally programmed re-replication?

The areas that undergo re-replication in the Sciara polytene chromosomes are called DNA puffs (to contrast them from Drosophila RNA puffs). The DNA puffs have undergone extra rounds of replication, and are templates for a massive amount of transcription that is translated into the proteins needed to make the pupal case in the next stage of development.

In both Sciara late larvae and in Drosophila follicles there’s a very short window in which a massive amount of protein is needed. In Drosophila it’s for the chorion that forms the egg shell, and in Sciara it’s for the pupal coat. And so the strategy in both systems is gene amplification. You might ask why other cell types don’t use the same strategy. The problem is that once you’ve undergone re-replication you now have nested replication forks and a structure called an onion-skin that is potentially very unstable when the cell tries to divide. But in both Sciara polytene chromosomes and the polyploid cells of Drosophila follicle cells there is no mitosis, so the onion-skin structure is not damaging. In addition, both tissues are destined to be destroyed soon after the re-replication event, so they wouldn’t have to live with the consequences anyway. If such onion-skin structures occur in dividing cells—such as in the cells that become cancerous—this might lead to breakage and recombination and eventually lead to amplification.

What have you learned about re-replication?

The first thing we had to do is to understand what an origin of replication looks like at the sequence level. This has been a very elusive target for the replication community because no specific origin of replication sequence has emerged for any organism except for budding yeast. Other organisms seem to have initiation zones rather than point origins, and no specific sequence. We developed a method that we called Replication Initiation Point (RIP) mapping. This was done with Anja Bielinsky, who was a postdoc in my lab. We needed an enriched population of newly replicated DNA to start with, and for this we popularized the use of the enzyme λ-exonuclease. This will digest DNA from its 5′ end in an exonucleolytic fashion, but not if there’s an RNA primer at the end, such as there is after re-replication. We first piloted the method using SV40 and then using yeast ARS1 [an origin of replication]. The ARS1 structure was very well established, but it wasn’t known whether there was a specific nucleotide where initiation starts, or whether it involves a larger area. We were able to show that indeed DNA replication begins at a unique start site. We were then able to identify where the Sciara DNA puff re-replication starts at the nucleotide level. There too we saw a unique start site for synthesis, even though there’s an apparently larger initiation zone seen by 2-D gels. Maybe at each end of the initiation zone there are preferred sites to start DNA synthesis, and that gives rise to the appearance of a zone.

Once we established where DNA synthesis starts in re-replication, we could look at the surrounding sequence and see if anything jumped out at us that might be a regulatory element. Directly adjacent to the start site, where the origin of replication complex binds, we found a potential binding site for an ecdysone receptor. This is the master regulator of insect development, and it was the first transcription factor ever discovered. We’re trying to test whether it is also acting as a replication factor. If so, the question is whether —in hormonally sensitive cancers such as breast cancer—the estrogen receptor might also serve as an amplification factor.

What role do you think the ecdysone receptor might play in re-replication?

We don’t have direct evidence it is a replication factor, only smoking gun evidence. But there is some precedence for transcription factors also acting as replication factors in certain animal viruses. In the case of Sciara we imagine a couple of scenarios. One possibility is that the ecdysone receptor is interacting with some of the replication machinery that’s sitting adjacent to it on the chromosome, keeping it in an “on” state. Another possibility of course is that it’s acting only as a transcription factor and triggering a cascade of events that lead to re-replication. The difficulty is you would expect this to impact all origins in the genome, not specific subsets. In Sciara there are 18 DNA puffs; what distinguishes them is still a mystery, but to me it suggests there’s something in the local environment—either at the sequence level or the chromatin level or in neighboring proteins such as the ecdysone receptors.

You are a great advocate for Sciara. What’s so compelling about this species?

Sciara is an amazing model organism with many unique biological features. Geneticists usually figure out how things work by making mutations. But, if you will, the unique features in Sciara are like God-given mutations; they are variations of canonical processes that can shed light on the underlying mechanism.

Around 1914 Charles Metz decided to study Sciara for his PhD thesis at Columbia. He captured it in the pigeon house at Cold Spring Harbor Laboratory on the suggestion of a friend. It took him quite a number of years to figure out the chromosome mechanics, but he ultimately succeeded and ended up dedicating his career to studying Sciara.

In the 1930s geneticists had a meeting at Cold Spring Harbor and realized that they would make more progress if they all worked on the same organism. They discussed which to choose, and the two finalists were Sciara and Drosophila. We all know who won! The reason Drosophila was chosen was because geneticists of the 1930s relied on making mutations by X-irradiation, and Sciara turns out to be extremely resistant to X-irradiation. This is another of its unique biological features, but it was not good at the time. Sciara surfaced again in 1970–71 when Sydney Brenner spent two years in the library trying to figure out a good model system for developmental biology. Sciara made his final shortlist of six organisms, but the winner of that competition was the nematode worm C. elegans.

Fast forward to the current time, and of course now we don’t have to rely on X-irradiation for mutation. Thanks to genome sequencing and other methods there’s been an explosion of emerging model systems where one can now reap the benefits of studying unique aspects of biology. In our lab, a senior staff member, Yutaka Yamamoto, has succeeded in developing a germline transformation method for Sciara. Moreover, former graduate student John Urban has sequenced and assembled the Sciara genome. Thus, we’ve established the toolbox of a genome sequence and a methodology to transform Sciara, so the time is now ripe for the scientific community to study all the unique features of Sciara. I’ve been trying to encourage other lab groups to start to work with Sciara. I’m thrilled that several labs have already started and others are on the horizon. We give a 1–2 day workshop in my lab for anyone who wants to learn how to work with Sciara.

What are some of the unique features of Sciara?

One is sex determination. There’s no Y chromosome, and sex is determined by the mother. There are two types of females: those with two copies of the X have only sons; those with one X and one X’ (an X with a long paracentric inversion) have only daughters. How that works is if the haploid egg came from an X/X’ mother, then the egg (when fertilized) will become a daughter. Whereas if it’s an egg from a mother that was X/X, the fertilized egg will become a son. Something, possibly in the cytoplasm, is conditioned by the mother at an early stage prior to meiosis when the X’ and X separate.

Spermatogenesis is also unique. In the first meiotic division in males there’s a monopolar spindle. Monopolar spindles have been studied in cases where they’re induced, but in Sciara it’s a normal occurrence. The chromosomes move from what looks like prophase, skipping metaphase, directly into an anaphase-like configuration, and ultimately telophase. What’s remarkable is in the anaphase-like configuration all the paternally-derived homologs move towards the nonpolar end of the spindle. That’s instead of it being random whether a maternally derived homologue will go to one pole end of the spindle or the other. This was the first example of imprinting, where the cell can recognize the paternal or maternal origin of chromosomes. It was noticed by Helen Crouse, who worked with Metz for a few years, and she coined the term imprinting in her 1960 GENETICS paper. It was later studied much more in-depth in mammalian systems, but it is not yet clear whether in Sciara it occurs by modification systems, such as methylation, as it does in mammals.

So, all of the paternally derived homologs move away from the single pole and are then discarded in a little bud of cytoplasm. In a way, this is a system en route to parthenogenesis because—at least in sperm—it’s not using the paternally-derived chromosomes of the previous generations. The chromosomes that move towards the single pole are maternally derived, and of course, how chromosomes move to this pole is a fascinating subject that is worthy of study in itself.

Then in meiosis II a bipolar spindle is established, though there’s only a single centrosome at one end, the one that came from the previous monopolar spindle. So now the chromosomes do align on a metaphase plate and then segregate, with the exception of the X. The X instead stays locked into the single centrosome, and the result is two products of meiosis II: one is nullo-X and the other has two copies of X (the X dyad). The nullo-X product is also encapsulated in a small bud of cytoplasm and degenerates. So, the only product of spermatogenesis is a single cell that has two copies of an X and is haploid for the autosomes. At fertilization, you have one X from the egg and two from the sperm, and the zygote ends up with three copies. But, of course, you can’t keep doing this every generation! You would accumulate more and more X chromosomes. So, in an early cleavage division some of the X chromosomes are eliminated.

And this is where sex determination comes into play: if the offspring is going to be male, it eliminates one of the three Xs; if the offspring is going to be female, it eliminates two of the three Xs. The final chromosomal complement in the soma of males is a single X, and females are either X/X or X/X’. Now imprinting comes into play. The eliminated Xs are always paternally derived. The X chromosomes that will be eliminated line up on the metaphase plate and start to separate—in that their centromeres disjoin and start to be pulled to one pole or the other—but the arms of the Xs fail to separate. So, it’s as if there’s a chromosome-specific failure of the cohesins to dissolve.

It turns out there’s a region that was genetically identified by Crouse that she called the controlling element (CE). It governs the X dyad nondisjunction in meiosis II, as well as the X chromosome elimination in embryogenesis. You can move the CE locus to any of the three autosomes by reciprocal translocations, and now you’ve fooled the cell into treating the autosomes as if they were the X: The translocation autosome will undergo non-disjunction in meiosis II and chromosome elimination in early embryogenesis, and the X that now lacks the controlling element no longer undergoes those unique behaviors.

What is the controlling element and how does it regulate these processes? We’d like to know more. The controlling element is located within the tandem array of 50 copies of ribosomal RNA genes—it’s right in the middle of the array and is flanked by translocation breakpoints. So, we would like to be able to zero in on it with long read sequencing and terrific genome assemblies. We know already know there is some non-rDNA sequence within the tandem array which in itself is interesting – then the question is what part of that is functional and how does it function. Is it, for example, like the XIST locus, which creates an RNA that coats the entire chromosome? That’s one hypothesis because the controlling element acts on the chromosome on which it’s sitting.

In addition to the sex determination mechanism and the unusual behaviors imparted by the controlling element, Sciara also has germline-limited chromosomes called the L chromosomes, whose roles are totally unknown. And, in addition, Sciara has locus-specific re-replication in DNA puffs of polytene chromosomes and other unique features.

Who have been your most important mentors?

Joe Gall without a doubt, and I’m still in very close touch with him. He’s most important cell biologists of our generation. He was always fascinated by the biology uniquely offered by particular eukaryotic species, including less well-studied organism, and that was one reason I went to study with him. He wasn’t wedded to one biological system, but being such a well-rounded biologist he would ask, what is the best biological system to study the question at hand? Rather than the other way around, which is, I have this biological system, now what questions can I ask with it? I think that’s what makes him quite remarkable and unique. A sequel lesson learned from that is it’s safest if we do experiments in a biological context—rather than try to dissect everything through test-tube biology or even cells in culture. I’ve always tried to do experiments in the biological system itself because then you’re less likely to have changes in unknown parameters that will give you the wrong answer.

What’s the best advice you ever received?

My colleague at Brown Art Landy once gave me some advice when we were worried about being scooped. He said if you know the answer to the experiment you are doing, you can jump ahead to where that was going to take you and plan the next experiment. If others arrive at a conclusion that you trust, then you can simply fast forward to the next logical question.

What advice would you give to younger scientists?

Treasure your exceptions. Sciara is an exception to the way things normally happen, but it can give you an enormous amount of insight into the basic canonical mechanisms that are shared by most other organisms. If you get a result in the lab that is unexpected, don’t throw up your hands in despair and say, things aren’t working, and I must have done something wrong, and this is not what the field would have predicted. You may in fact have opened up a whole new line of pursuit! After you repeat it and do the appropriate controls, it could change the mindset of the field and let people know that the current hypothesis or model might need some tweaking.

David Kingsley

The Genetics Society of America Medal is awarded to an individual for outstanding contributions to the field of genetics in the last 15 years. Recipients of the GSA Medal are recognized for elegant and highly-meaningful contributions to modern genetics, exemplifying the ingenuity of GSA membership.

The 2017 recipient is David M. Kingsley, whose work in mouse, sticklebacks, and humans has shifted paradigms about how vertebrates evolve. Kingsley first fell in love with genetics in graduate school, where he worked on receptor-mediated endocytosis with Monty Krieger. In his postdoctoral training, he was able to unite genetics with his first scientific love — vertebrate morphology. He joined the group of Neal Copeland and Nancy Jenkins, where he led efforts to map the classical mouse skeletal mutation short ear. Convinced that experimental genetics had a unique power to reveal the inner workings of evolution, Kingsley then established the stickleback fish as an extraordinarily productive model of quantitative trait evolution in wild species. He and his colleagues revealed many important insights, including the discoveries that, major morphological differences can map to key loci with large effects, that regulatory changes in essential developmental control genes have produced advantageous new traits, and that nature has selected the same genes over and over again to drive the stickleback’s skeletal evolution. Recently, Kingsley’s group has been using these lessons to reveal more about how our own species evolved.

An abridged version of this interview was published in the December 2017 issue of GENETICS.

What inspired you to become a scientist?

My dad died of cancer when he was 34. As a little kid I was aware that you don’t know how long you have left, and I grew up wanting to make sure I spent the time I have doing something interesting and important. I thought that tackling age-old mysteries about life’s origin and mechanisms was a good way to spend my life.

What did you learn from your first mentors?

I was a kid who loved dinosaurs and skeletons. That interest was nurtured by a great high school teacher, Jack Koch at Roosevelt High School in Des Moines, Iowa. I dedicated my PhD thesis to him.  In his advanced biology class we memorized the names of every bone and muscle in the cat and human skeleton. A lot of people hated it, but I loved it because you could see so much about the function and lifestyle of the organisms from the size and shapes and patterns of bones. I’m lucky because I still work on skeletal anatomy and evolution!

In graduate school, I fell in love with the power of genetics. I had a set of teachers at MIT, including David Botstein and Monty Krieger who helped me learn that with genetics you didn’t have to assume anything about the answer. You didn’t have guess you were looking for a particular type of molecule or anything like that.  Genetics was an algorithm that would take you to the key components controlling a biological system no matter what they were. I saw how genetics had the power to dissect old, hard problems like cell cycle and development, which had been mysteries when I first came across them in biology class.

Why did you choose to work on the short ear gene?

As a postdoc, I got to bring together my love of genetics with my love of vertebrate morphology — I went to a mouse genetics lab where they were among the first to walk down chromosomes and identify the molecular basis of classic mouse mutations. In graduate school, I had heard a great seminar from David Hogness from Stanford, who was carrying out some of the first chromosome walks to the homeotic genes in Drosophila. Here was someone studying one of the most interesting morphological problems you could imagine: how to turn one body part into another. He was turning morphology into genes and DNA and sequence and development, and I thought that was electrifying. I could see that mouse would go through the same revolution that had come to fly.

Vertebrate genetics takes a long time, so you should pick your problem carefully. I didn’t want to pick something that was better studied in bacteria, yeast, or powerful invertebrate systems. The skeleton was perfect; it’s the defining feature of vertebrates. It also plays such an important role in animals’ external appearance that many classic mutants had already been picked up in simple morphological screens.

Near the end of grad school, I took out from the library “Genetic variants and strains of the laboratory mouse” and read the whole book—one mutant after another. We decided to go for the short ear gene, which had been worked on for decades by the person who put that wonderful book together—Margaret Green from the Jackson Labs. She was both a very perceptive scientist and a great editor and collator. So, I felt like I was dipping into one of her favorite mutations, but there were also practical reasons to choose short ear. After World War II there had been a lot of interest in the effects of radiation on the mammalian germline, and there were two big mouse forward mutation experiments in the UK and US. They both used a test strain carrying seven homozygous recessive mutations with visible phenotypes. These were six pigment mutations and short-ear.

Millions of wild-type mice were mutagenized and crossed with the test strain to measure the rate of recovering new alleles at any of the seven loci.  As a result, there were lots of newly induced mutations, including a whole set of deficiency chromosomes that took out both short ear and one of the closely linked pigmentation loci.  We essentially had the equivalent of a Drosophila genetics playground for this particular region of the mouse genome! We would be able to orient ourselves using the same kind of deletion breakpoints that Hogness had been using in flies. And my postdoc advisors Nancy Jenkins and Neal Copeland had already found a retroviral insertion that caused the closely-linked dilute coat phenotype, so we even had a good entry point that was within a millimorgan of the short ear gene. That was one of the reasons why I chose short ear out of the 150 or so classic skeletal mutations.

What did you learn from the short ear project?

It took about five years to do the chromosome walk in the region, and I was already an assistant professor by the time we eventually isolated the gene for this classic skeletal trait. But it was incredibly gratifying. The gene controlling skeletal morphology encoded a secreted signal already named a “bone morphogenetic protein” (BMP).

It had been named by biochemists who found that if you took an adult bone and ground it into powder and injected it under the skin of an animal, there was some magic ingredient that could generate a brand new bone at the site of implantation. And if you put the implant in the shape of a circle, for example, it would come out as a circular bone, so you could even see that the pattern in which the signal was expressed controlled something about the rough shape and morphology of the bone that resulted.

The short ear mice provided the first genetic evidence that BMPs were the endogenous signals that vertebrates were using to set the form and pattern of skeletal structures. If you had a mutation in one of the BMPs you very selectively removed the aspect of skeletal morphology controlled by that particular member of the BMP family. The short ear deficiency strains turned out to be important because they included 29 alleles at the short ear locus, of which half a dozen were regulatory mutations disrupting the flanking DNA. These later helped us to identify a whole series of modular, remarkably specific enhancers controlling different aspects of skeletal morphology.  We think of them as anatomy elements because they might control expression for example in just the ribs, and maybe only in a 90-degree sector on the outside of the ribs. There would be a different controller for the inside of the ribs, allowing you to tune the overall shape. For someone originally interested in those beautiful piles of bones, to be able to break down their shapes into the expression patterns of secreted signaling molecules was an incredibly satisfying answer.

Why did you choose sticklebacks?

If you can find a way to turn old biological problems into genetics problems, then you can often find the answers to even intractable questions. A brave postdoc Katie Peichel and I spent a really fun summer in 1998 figuring out how to turn classic evolutionary questions into a genetics problem. We wanted to identify the number and type of genes and mutations that control species differences in nature. The trick was to figure out some way to cross different species, which sounds paradoxical because one definition of species is that they are reproductively isolated. The loophole is that reproductive isolation can occur through either postzygotic or prezygotic mechanisms. Postzygotic mechanisms include inviability and sterility, which are obviously hard to overcome.  However prezygotic isolating mechanisms are things like behavioral or mechanical incompatibilities in mating, which can be overcome using artificial fertilization in the laboratory.

We went around talking to biologists, reading all kinds of books, looking for very young species with recently evolved dramatic skeletal differences that could still be crossed in the laboratory. We looked at wild mice and birds, but the thing that was attractive about fish was the clutch sizes tended to be very large. With a bird system, nests might have a couple of eggs, while a fish nest would have hundreds of thousands. For using a genetic approach, especially for mapping complex traits in the wild, the bigger the family size the better.

Somewhere in the middle of that summer, I found a great book chapter by Mike Bell of Stonybrook University talking about all the cool skeletal traits that had evolved in sticklebacks after the end of the last Ice Age. There was a remarkable previous literature on stickleback morphology, ecology, and behavior in new freshwater streams and lakes. And new forms had evolved not just once but thousands of times. That was because their main ancestors were migratory like Salmon and would come from the ocean into coastal areas to breed every spring. So, when the glaciers melted and lots of new lakes and streams formed, it generated all these brand new, empty environments that were colonized by sticklebacks. It was like nature had set off a replicate series of evolution experiments 10,000 years ago, producing new forms over and over again. That was beautiful to us because not only could we figure out how evolution worked in a particular lake or stream, but the system as a whole would make it possible to tell whether the mechanisms used in evolution have any repeatability to them. Is it going to be different every time? Or are there rules and principles that underlie the way organisms adapt to new conditions.

What did you learn about repeatability of evolution?

I had a debate with a fellow faculty member when I started the project because he thought the project was not worth doing. Firstly, because evolution is complicated, and if it’s controlled by lots of genes with tiny effects you’ll never find anything. But his killer argument was: even if you could do it, he wouldn’t care. And his reason was related to repeatability. He figured we would knock ourselves out trying to figure out what happened in one lake and all we would find would be historical minutiae that accumulated in that particular location, and that if you then studied a second place you’d get a different answer and then a third would give you a different answer again. It would just turn out to be postage stamp collecting, and there wouldn’t be any generality.

At the time, we didn’t have evidence one way or another. But my best reply was: how do you know? That was the great thing about genetics – it would tell you the answer no matter what the answer is. We could have learned that all the traits are controlled by tiny effects that are almost unmappable. And we could have gotten the answer that all those little tiny effects are distributed across the genome in a way that is just due to history. But that’s not what the genetics showed.

We started crossing these fish with huge skeletal differences. And by huge, I mean thirty-fold differences in the number of plates along the anterior-posterior body axis, or complete presence or absence of an entire fin, or doubling the number of teeth, or black fish vs. white fish, the kind of dramatic changes you would normally see between different genera of wild species. And we found that while none of these evolutionary differences were simple Mendelian traits, they typically had genetic architectures with one or two chromosome regions showing very large effects, perhaps explaining up to three-quarters of the variation, along with a handful of other modifier regions controlling five to ten percent of the variance. So, the genetics was manageable.

And if you compared the results from crosses done in different lakes, it tuned out the very same chromosome regions were being used over and over again in different populations. So even before we identified the genes, we knew this was going to be both interesting and doable.

We’ve subsequently taken lots of traits down to genes and molecules. We’ve found that key signals and transcription factors that developmental biologists have been studying for years turn out to be the same molecules that nature is using to redesign anatomical features.  And we’re finding the reuse isn’t just from lake to lake, it’s from organism to organism. For example, although we didn’t set out to test any particular candidate genes, the genetic data showed us that some of those stickleback skeletal traits are controlled by the same kinds of bone morphogenetic proteins that we found in mouse.

How does the stickleback work all connect with your studies of human evolution?

We’re interested in why particular genes are reused throughout evolution, and we’re also interested in applying the patterns we’ve found in sticklebacks to the evolution of ourselves. We’ve found that classic traits in people, like blond hair color, or height, are evolving in humans using the same types of key control genes and regulatory mutations we have found in fish. And unlike rare genetic diseases, there are derived alleles at these human loci where a large fraction of the population carry the selected version. So rather than studying diseases that affect 1 in 100,000 people, it’s been really interesting to study variants that, because they have been subject to selection, are now present in billions of people. In some cases, the selected alleles may actually increase susceptibility to late-onset diseases like cancer or arthritis. It’s not a huge effect, maybe 1.3 to 1.8-fold. But when an allele slightly increases risk of a disease and is carried by a few billion people through selection, then suddenly you find an awful lot of the burden of a common human disease is controlled by our own evolutionary history.

We’re now going back and forth between humans and the patterns we see in fish. We thought it might take us 50 years to get enough examples to pull out general principles, but it turned out to be much faster than that. We now have a whole bunch of genomic regions—maybe 200—that have been repeatedly selected in stickleback. We’ve been able to answer how often evolution uses coding versus regulatory genes. That question was debated a long time. However, we can now say empirically the answer is both, but 85% of the time it’s regulatory and 15% coding. When I say there’s things we learned from fish that we apply to other organisms, we’re already applying things like that 85 percent rule in our human studies. If regulatory changes are by far the most common way to preserve viability and fitness when sticklebacks are evolving under a whole range of fitness constraints. then I think the things that make us human are likely to also be regulatory. So, we can prioritize our human work using the rules we learned from repeated evolution in stickleback.

What’s the best advice you ever received?

Genetics can be used to study anything.

What advice would you give to younger scientists?

Genetics can be used to study anything! I fell in love with genetics watching it be used by people who loved it. It’s such an honor to receive this award because I feel like I’m continuing that tradition— especially since it has previously been given to many of my own teachers and heroes in the field. I hope my students will also be convinced of the power of genetics and will use it to study their own favorite problems as well.

Sally G. Hoskins

The Genetics Society of America’s Elizabeth W. Jones Award for Excellence in Education recognizes significant and sustained impact on genetics education. The 2017 recipient is Sally G. Hoskins, in recognition of her role in developing and promoting the transformative science education method CREATE (Consider, Read, Elucidate hypotheses, Analyze and interpret data, and Think of the next Experiment). This innovative approach uses primary literature to engage students, allowing them to experience for themselves the creativity and challenge of study design, analysis, interpretation, collaboration, and debate. Comprehensive evaluation of CREATE has consistently found that students improve in difficult-to-teach skills like critical thinking and experimental design, while showing improved attitudes and beliefs about science.

An abridged version of this interview is published in the December 2017 issue of GENETICS.

What inspired you to become a scientist?

In the seventh grade, we got to dissect a worm, and I just loved working with my hands and with a dissecting microscope and seeing what was inside—I was very captivated. I worked on retina development and frog embryos for a long time; they’re very beautiful, and I continued to enjoy the hands-on aspects. It’s kind of weird though, because if you meet people at a party and you say you’re a scientist, and they say, “Eww, you dissect frogs!”, then I have to say, “Yes, I conform to all your stereotypes.”

What’s your most memorable moment from your career so far?

In grad school, I was working on a frog retinal development question, and I had this idea of how to do one of the experiments by “birth dating” of cells, where you tag them with a radioactive label. It was a bit of a complicated experiment, and my advisor didn’t really want radioisotopes in the lab. Anyway, when I eventually got to do it, and I developed the first set of slides and put them under the microscope, I realized it had worked. I could see the sharp dividing line between the labeled and the unlabeled retinal cells, and I was like, “Oh, wow! ”

I had the idea, I fought for the experiment, the experiment worked. That was a good feeling.

One of the things we do in CREATE is interview the authors of papers by email, using students’ questions. In one of our courses recently, Elaine Ostrander, who works on dog genetics, did a phone interview where the students asked what she liked best about being a scientist. She said something along the lines of: “I love that moment when you look at the data, and something comes together, and you figure something out, and for that moment you’re the only one who knows it. And you savor that discovery before you call the rest of the lab.” It was nice to have somebody articulate that for our students. Unfortunately, the image of scientists is very distorted in pop culture, so it’s nice for students to get behind the scenes and learn scientists are simply people who love trying to figure things out.

Why did you choose to focus on primary literature as a teaching mode?

It grew out of my teaching at City College. I really hated lecturing and I had had some very good teachers in undergrad and grad school who used literature in classes, and so I started to introduce that approach. CREATE came about because I’d been giving out papers with the very poor approach of just saying to the students, “read this.” I’d be miffed that they didn’t really have a lot to say about the paper. It’s a big jump from reading textbooks to reading papers, and I hadn’t helped them at all.

Then at one point while we were studying a paper, a follow-up paper came out, and I thought it would be cool for them to read it. But the second paper was so much easier for everyone that a light bulb went on for me. Now everyone understood the set-up, and the technology, and the basic question, and they also now cared about the questions. So, I realized it would be smart to do these papers in series. Then my collaborator Leslie Stevens and I further developed the idea by first figuring out how we had learned to read papers in grad school, and then codifying that process to guide students through deep analysis of study designs and the data produced.

No offense to textbook authors—I know there are some really heroic efforts going on to write new kinds of textbooks—but in general textbooks are easier reading than the original papers because they simplify papers drastically. But if our students get out into the world, if they do science they’re going to be reading papers, not textbooks. It’s a skill that’s worth learning, and it’s not as hard as it looks, it’s just that the jargon is so dense and the initial hurdle is high. Some students have also developed this habit of just reading the abstract. If you’re in a class where papers are “read” really fast, and you have to get through 30 papers in a semester, then the abstract may be all you need. But we wanted to go slower and deeper, basing it on how we learned this skill in grad school.

CREATE has been successful, and we’ve tweaked and expanded it in various ways. For example, we started it as an elective course for upper-level undergraduates, a focus course to be taken after you’re taken your pre-requisites. Then we realized there are some advantages to introducing this kind of thinking and science literacy in the Freshman year, so we have a version of it for Freshmen. We also have tested it with success in two-year colleges.

What is the most rewarding aspect of your work?

I think the most rewarding aspect is the idea that you’re teaching students that they can figure out how we know what we know—not just what our current state of understanding is. The papers provide enough information to take you inside the lab or into the field, if you delve deeply. Plus, students develop transferable skills of critical analysis. You’re teaching them approaches and learning strategies that they can apply to any future challenging or analytical task. Biology is changing so fast. There is maybe 30 years’ more stuff in Intro Bio than when I took it. But the semester is still the same length. So, if you do the math, it doesn’t work! How can we keep putting more and more information into these semester-long courses and expect the students to be able to learn it, retain it, and apply it? With CREATE we don’t try to do that, we try to teach an analytical skill set and an attitude that you can take with you, along with a deeper understanding of both how research is done, and the people behind the papers.

It’s not like teaching Intro to French. OK I’ve never taught Intro French, but I would guess that you could teach it the same way for 30 years. Maybe there’s a new theory of language teaching, and I’m wrong, but still, you have to learn the present tense and you have to learn the possessive form and the vocabulary words and so on. Yet biology has really changed a lot, and I don’t know that our teaching is reflecting that. For example, there’s probably been six different ways to clone that have come and gone since I was an undergrad. And maybe now someone would just sequence the genome instead!

We approach science as an open book activity. People don’t go to their labs and do everything from memory, including making media, calculating antibody dilutions, and the like. But when we evaluate learning only through closed-book tests, that’s the skill we’re saying you need. CREATE doesn’t emphasize memorization. We emphasize putting ideas together, thinking, logic, collegial argumentation, and creativity.

I’ve run a lot of workshops with faculty from a wide range of institutions, and all of them say, “Yes, my students took  multiple pre-requisite courses, and no, they don’t come into my class knowing what they “should” know from the pre-requisite classes.” So, I think something is wrong. Part of the reason may be that most college teachers, including myself, had no training in teaching or in the science of learning. This is a well-kept secret from people’s parents, that their kids could be being taught by somebody who’s never been in the classroom before; or even if “experienced”, someone lacking training. Your third-grade teacher has studied something about teaching and learning, and has student-taught and been observed in the classroom, and that’s not true for most scientists. Things are changing, but still some college faculty have this boot camp kind of thinking: “Well I went through it (being taught only through lectures), so why can’t you?” Maybe there’s a better way. Maybe there’s a way that would not just get students through biology, but also get them excited about it.  Many people are working on this; our way is through in-depth analysis of primary literature.

Who have been your most important mentors?

My students. Because of the feedback you get about what’s working and what’s not. Let me give you an example. Around the time we started CREATE I’d had a PhD for 20 years and had been teaching in college for 15 years, and I didn’t even know science education journals existed! That’s how out of it I was. A colleague brought me a bag of books about teaching and learning and I realized, “Oh my gosh, people actually study this!”

Anyway, I read up, and I wrote a grant on my sabbatical. It was totally hypothetical, we didn’t have pilot data. But the grant reviewers really loved the idea, and we got the money. We started teaching the course, and it immediately started flopping. It was not working at all. I didn’t understand. The grant reviewers had loved it, and we were doing what we said we would, so what was wrong? It turns out that when scientists read a methods section, they can visualize what happened. But when students “read” the methods section, they either weren’t really reading it or else they weren’t reading it with an eye towards picturing what went on in the lab. And when I added a “sketching,” step—where they draw in their notebook how the study was done in the lab or field to generate the data represented in each figure—that was when everything started to work. The class was much more lively, and people were “getting it” and having things to say, rather than just limping along or waiting for me to revert to a lecture. Discussing the data made much more sense once students “saw” where it came from. You can’t fake a sketch; to produce one you must read the methods closely. That made a huge difference. So it was the students who revealed that there was a gap in the approach, and it turned out to be really key to the whole thing—we needed to add a visualization step.

What would you say to someone concerned about trying the CREATE approach?

Some faculty, especially (and understandably) if they are only evaluated through student reviews, are very afraid of students’ negative reactions to any change in teaching. With CREATE we’ve generally had around 75 to 80% positive reaction. We’ve also always looked at both cognitive gains, like critical thinking or experimental design, and effective gains, like students’ attitudes and epistemologies of science. I’m really happy that we see significant positive changes in both. So, it’s not that CREATE makes you feel better about science, but you don’t learn anything.  The strategy affects students in multiple ways, building transferable thinking skills along with positive views of research/researchers.

There’s a big issue with science education reform where people say, “I would like to change but I can’t because I have to cover content.” But a) covering is not teaching, and b) CREATE includes content! To really understand a paper, you’ve got to understand key content. A huge amount of content is reviewed and consolidated in a CREATE class, but it’s in context. In fact, you have a lot of opportunities in a CREATE classroom to integrate the sciences, for example quickly reviewing some of the underlying principles of chemistry or physics, that are associated with the experiment you’re studying.

Some people are also a bit iffy about the e-mail interviews of authors. But the things we learn from the interviews are profound. Dr. Elaine Ostrander, a Distinguished Investigator and Comparative Genomics section head at NIH, was asked what happens if an experiment doesn’t work and a hypothesis must be discarded, and students always assume the answer will be “Oh, I feel so bad, I want to die!” But there are many rejected hypotheses on the road to success, which is not something you really learn in many Intro Bio labs. So, when Elaine Ostrander got that question, she said, “If all your experiments work, then you really aren’t asking very interesting questions.” Failure is a normal part of science. If I had learned that as a sophomore, it would have changed me!

Another cool thing that happens with the e-mails is the insider info you can get. We read two papers that had been published back-to-back in Science about regeneration and the Wnt pathway of Planaria. One lab had knocked down one molecule in the pathway and their animals regenerated tail-tail. And the other group altered a different part of the pathway and got head-head. We send the same questions to the grad students and postdocs as we do to the PIs. When we wrote asking how they set up the back-to-back publishing, one post-doc said, “I went to a meeting and I was going to present my tail-tail stuff and saw another post-doc present the head-head stuff. So, I called my PI and the two PIs discussed it and we decided to not communicate for three months and then publish together.” In class, we discussed alternative ways the PIs might have reacted. We got a lot of mileage out of closely comparing the two papers; the students pulled out all the similarities and differences in experimental paths taken by two different groups to reach the same basic conclusion. So, the e-mails really complement the deep understanding of the papers by putting context around it and making it clear that these studies are done by “real people” who remind my students of themselves, and not only by famous senior PIs.

Ultimately, for change in education, you have to get the teachers to change what they do. And that’s challenging because for many people teaching can’t be their number one focus. When we invented CREATE, we felt like we were really helping in that regard, in the sense that we were leveraging people’s deep understanding of research that they didn’t get to bring to class because they were busy lecturing, lecturing, lecturing. Professors’ understanding of how research is done and critically evaluated, built over years of study, comes into play in virtually every CREATE class. You can switch over your upper level elective to a CREATE course pretty easily, especially if the elective is in your area of expertise. I think it’s valuable for students to realize that their faculty are serious researchers and not just PowerPoint presenters. I understand that there are multiple pressures on people these days, but I think this is a much more fun way to teach. It’s not just that it’s good for the students, there’s a big payoff for the faculty as well. Unless you really love your PowerPoint.

What are you currently working on?

I have a collaboration with Kristy Kenyon and Stanley Lo following up with faculty who use CREATE. We’re interested in what it takes to change a teacher’s approach. There are a lot of different workshops and training on alternative ways to teach, but there isn’t a lot of evidence yet that they have a lasting effect on teachers. We’re trying to help with course design by posting tested CREATE modules on our website, www.teachcreate.org.

Of course, we’re also interested in the effect of CREATE on students. We’ve been looking at the extent to which CREATE shifts students; perspectives on science to be more like experts’ perspectives. The interesting thing is that CREATE courses don’t have a hands-on component, and yet we’re seeing a lot of shifts in student thinking to be more like that of someone who holds a PhD.

Another project is a collaboration with Alison Krufka of Rowan University on a variation where you take a traditionally taught course, and you take just two weeks to do CREATE. We’re testing whether a small dose of CREATE will have an impact or not. We also have a project on a new approach to using CREATE in introductory biology at community colleges. We originally designed it for upper-level courses, and then we designed a scientific thinking course for Freshmen. But what if you have to teach Intro Bio with ten major topics? Is there an easy way to use CREATE there? We’re just analyzing the data now on whether you can increase student understanding by using CREATE modules focused on the major themes that you always find in Intro Bio, like meiosis, rather than purely textbook teaching.

If you weren’t a scientist, what would you be?

Maybe something in music, which has been an important part of my life. I founded a womens’ chorus in Manhattan and ran it for about seven years. I also like design. Again, it’s working with your hands and making things.

What advice would you give to younger scientists? 

Be bold! Take advantage of opportunities like visiting the Marine Biological Lab in Woods Hole or calling somebody up and asking, “Can I come to your lab to learn this technique,” or “Can we collaborate?” Don’t try to do everything yourself. Be willing to collaborate and travel and meet people widely. It’s hard for every person to do every technique. Don’t be shy about asking for help. I think one thing that comes out in the CREATE e-mails with scientists that I kind of like is that people come across as quite open and friendly. Students comment, “Wow, I didn’t think she would answer in such detail,” or “I didn’t realize that scientists collaborated or that you could call somebody up and they would send you antibodies.” So, I think as a young scientist you may not have realized that yourself; even if someone is a big shot, try to chat to them at a meeting or talk to their postdoc. Many people really enjoy sharing their knowledge, so don’t be so intimidated by rank. Give yourself a lot of different experiences. Sometimes you’ll do something like to go to Woods Hole and suddenly, boom! You meet somebody there, and you realize, “now I just have to go to Italy and work on squid because I’ve fallen in love with this system.”

And also, there are all kinds of ways to be a scientist, so if you do an undergrad research project, and you’re not thrilled with bioinformatics, for example, there are a million other things you could do. One thing nice about CREATE is that you can teach diverse modules where, say, one is all about regeneration in Planaria, and one is all about behavior in ants and so on. Some people love doing field work and some people would never do field work and some people would never sit and look through a microscope all day; there are distinct research options available for all these individuals. Intensively analyzing papers in different fields can give you a taste of what the work is like.

Are you a postdoc looking for hands-on education experience and mentoring? Or a faculty member interested in bringing evidence-based, effective active learning strategies into your classroom? The PALM (Promoting Active Learning and Mentoring) network helps faculty and postdoctoral fellows gain hands-on experience and long-term mentorship in putting active learning strategies into practice.

GSA is proud to partner with the American Society for Cell Biology (ASCB) and the American Society of Plant Biologists (ASPB) in the development of the PALM network. In addition to resources and support, the program provides up to $2000 mentoring visit expenses per fellow, $500 mentor stipend, and $1000 meeting travel each for both fellow and mentor.

We spoke to one of the first PALM fellows, Christopher Baker, and his PALM mentor Michelle Smith to learn about what makes this experience so valuable for both the mentors and mentees.

Christopher Baker

Baker is an Assistant Professor at the Jackson Laboratories (JAX). He was a PALM fellow during his postdoctoral training (also at JAX), working with Smith to design and teach classes at the University of Maine. He investigates the genetic and molecular regulatory system that controls the location and rate of meiotic recombination.

Michelle Smith

Smith is an Associate Professor of Biological Sciences at the University of Maine. She is a science education researcher whose work focuses on how to help students learn biology and how to help faculty adopt promising educational practices in their classrooms.

Why were you interested in the PALM program?

CB: At JAX, we don’t have as many teaching opportunities as at a university, although we do have a few options, including graduate classes and a college-level genetics course for JAX employees. I had interacted with Michelle a little in courses at JAX, including one for grad students and postdocs called “The Whole Scientist” that filled out training on the non-research aspects of being a scientist. Michelle talked to us about teaching and introduced the concept of active learning methods. I realized that meeting Michelle was a great opportunity, and she was someone who could help me get into the classroom and get some more experience. I observed her in the classroom and had asked about the possibility of teaching a few classes at U Maine. When we heard about the PALM fellowship, we thought it was the perfect chance to do just that.

MS: I knew about the PALM program through my involvement with the GSA [Smith serves on the GSA Education Committee]. I think instructional coaching opportunities are really valuable, and I was interested in providing that mentorship. Chris and I were thinking about doing something like this anyway, but we realized the PALM program would provide us with extra support and opportunities. It would allow us to see the project all the way through, from having an idea, collecting student learning data, and analyzing the data, to revising the classroom materials.

Why do you think the PALM program is important?

MS: It’s the next step in getting people into active learning 2.0. It’s been shown that active learning methods are more effective for students, but how do we actually get instructors to use them effectively in the classroom? Many instructors first become interested in active learning through a workshop or seminar, but when they try using the methods in their classes, they can get really bogged down in the logistics—like, how do I ask a clicker question? How long do I give them for discussion? PALM gives postdocs a chance to practice in an environment with someone there who’s got your back and can help out.

Chris, what teaching experience did you have before applying?

CB: I had never taught a course or given a lecture in a large-enrollment undergraduate setting, although I had helped teach some study sections. I had enjoyed giving public lectures and talking about my research at local middle schools, so even though I didn’t have formal experience, I did like the idea of teaching.

What was your goal?

CB: I wanted to get some first-hand experience of some of the active learning concepts that Michelle has helped pioneer, particularly the use of in-class clicker content questions that are accompanied by peer discussion. Basically, that’s giving the students a question and getting them to answer it, then getting them to talk among themselves in small groups and then answer again. That peer instruction gives them a chance to think through the question and to have to explain their reasoning aloud. I thought that interaction, and what it takes to facilitate it, was really interesting. I also generally wanted experience with putting together class activities that encourage students to interact with one another.

How did you work together?

CB: Michelle had a large-enrollment course in genetics with several classes on meiosis and recombination, which is what I was studying. So, we came up with concepts that we could build the classes around and made an outline. I spent some time putting together potential genetics problems that could be incorporated into clicker questions and reviewing and editing Michelle’s current lectures on the topics. Then we met over two full days to review my material, which was super helpful. We also used the time to flesh out the mechanics of what was going to happen in the classroom, how to manage technology and, hopefully, the class. I taught my lessons over two class periods in the same week. Having two classes was very helpful, as it allowed us to review how things went during the first class. It also gave me more confidence to relax into the role.

MS: One of the nice things was that, because there were times when the students were discussing clicker questions with each other, we could communicate while Chris was teaching—in real time. For example, after he’d asked a question, I could come up and say: “OK, here’s what we can do next”, or “maybe you could try this”, or “remind them about that”. Often when you try active learning for the first time, it can be really daunting to let the students talk to each other and volunteer their answers because you don’t know what to expect. It helps to have someone else there to say, “It’s OK, I’ve seen this before,” or “you’re probably going to get this answer.”

CB: That was really useful. I almost wish we could have the same thing for presenting at a research conference! Someone to say, “OK, let’s all take a break now.”

MS: The other thing that was important was involving the students in the process. There’s a lot involved in turning over your class to somebody new. At this point, it was midway through the semester, and active learning involves building a lot of trust with the students. To help with this, I talked to them about why Chris was coming, and told them about his expertise, and then at the end I asked the students to give him feedback. That was nice—he did a recombination demonstration with pool noodles, and they wrote about how that really helped them visualize the process. But it also helped the students to see Chris’ involvement as part of a larger plan and see themselves as partners in helping Chris out.

CB: One of the goals of the PALM fellowship is also to disseminate our experiences to the wider community. In part through support of the PALM program, Michelle and I attended The Allied Genetic Conference in 2016, which had a significant education component. We presented a poster incorporating analysis of the students’ and instructors’ time spent engaged in active versus passive learning, as well as student assessment and feedback.

How was this experience useful for your careers?

CB: When I was on the job market and interviewing at universities, I was often asked about the program. I think people were interested, particularly at places where active learning techniques hadn’t been promoted much in the past. It certainly caught people’s eye, and it was helpful. I ended up at an institute that’s primarily focused on research, and I don’t have an undergrad classroom, but I try hard to incorporate peer discussion into my graduate teaching. 

MS: A lot of times people focus on the benefits of these programs to the mentee, but there were a lot of benefits to me as well! For example, Chris taught about meiosis and recombination, which is his research area. I had been teaching meiosis and recombination for many years, but for me it had become a bit predictable, and I was using the same types of problems every time. It was great not only that he provided new content, but also that he helped me step back a bit and think about why we have students learn about this topic.

The experience also helped me think through what I actually do in the classroom. For example, there are things I do to get ready that are important to me—like making sure the slides are posted ahead of time or making sure I run through the clicker questions—but I hadn’t verbalized those aspects. I promote active learning, but what are the steps that are actually involved when you put it into practice? Having to reflect on that has really helped me with the education workshops I give.

For mentees, I’d also point out this program can open doors to publishing education research. For example, there are places like CourseSource where you can publish the activities you develop.

Do you have advice for people thinking of applying?

MS: My advice is if you’re at all interested, to go for it. If you’re concerned about finding a mentor, or don’t know where to start, I would encourage you to reach out to Sue Wick at the ASCB. She will help answer your questions, assist in finding a mentor, and help you solve problems. Don’t let anything on the application intimidate you.

CB: If you have any interest in teaching, it’s a really valuable experience to be involved in a program like this. Get involved and have fun; it will be worth it!

Learn more about the PALM network here!