Parental chromosomes separate during meiosis and segregate into sex cells, like sperm or egg, transferring genetic information to the next generation. For successful inheritance to occur, chromosomes must communicate with each other to ensure they remain intact throughout the process. Ofer Rog, who is Associate Professor of Biological Sciences at the University of Utah, employed cutting-edge genetics and high-resolution microscopy to probe local and chromosome-wide physical changes during meiosis to understand their function in chromosome inheritance.

Unraveling chromosome biology  

Rog considers himself privileged to be doing science. Since he started college, he was surrounded by people who were doing research, allowing him to envision a career in academia. “I had crucial connections that helped me land a PhD position in a top-notch research institute in the UK,” says Rog. Since then, Rog has been dedicated to understanding chromosome biology. 

As a PhD student in Julie Cooper’s laboratory at the University College London, Rog showed that a DNA-binding protein is required for replication forks to pass through telomeres. This was a dogma-shattering observation since the prevailing view was that DNA-binding proteins are barriers to replication. Continuing his work in chromosome biology as a postdoc with Abby Dernburg at the University of California, Berkeley, Rog embraced cell biological approaches and dissected molecular mechanisms of chromosome interactions. He first developed tools for high-resolution live imaging of chromosome dynamics in C. elegans and visualized the structure-function relationship between protein complexes that latch onto chromosomes. He provided the first direct observation of a protein network assembly onto parental chromosomes, where many proteins form a railroad-like zipper structure between parental (homologous) chromosomes to regulate exchanges during sexual reproduction. He further discovered that this structure is not static and rigid, as was widely assumed based on electron microscopy images, but rather a liquid-like dynamic compartment.

“Rog developed a cytological method to measure exchanges between sister chromatids in meiosis using pulse-chase experiments. Before his work, exchanges between sister chromatids were effectively invisible since sister chromatids are genetically identical,” explains Lisa Kursel, a Research Assistant Professor working in Rog’s laboratory at the University of Utah.

Launching his independent research group on the back of these remarkable discoveries, Rog now investigates the broader implications of the liquid-like state of the chromosomal-protein complex structure on genetic exchanges during meiosis and on cellular health. “We are interested in why the structure of the protein-chromosome complex behaves as a liquid. We hypothesize that the structure allows communication between different molecules in a very controlled way where the molecular signal diffuses inside a compartment instead of spreading to all directions at once. We are also interested in how this liquid structure can bring and hold chromosomes together to exert force on the genome and shape it into chromosomes,” says Rog. He is now combining powerful stimulated emission depletion (STED) microscopy and cryogenic electron tomography to look at molecular structures and how they manifest in the complex organization of chromosomes.

A terrific role model with a passion for science communication

Rog is the first openly gay faculty in the College of Science at the University of Utah, and he deeply values inclusion. “It is important to have visibility and have everyone’s voices heard. I have made sure to provide space for members of the LGBTQ community,” he shares. Rog used his position and influence to create changes within his research community, founding an LGBTQ+ STEM group at the University of Utah where he invites LGBTQ+ speakers to campus and discusses their inspiring research journey with students. Rog is also advocating for diversifying science along other axes as an early career researcher. “I think we currently have a lot of walls, such as people coming into a biology PhD from a non-R01 university or non-western countries. We want to hear how people in leadership positions can make science inclusive and bring down walls in the scientific community,” says Rog.

Lisa Kursel describes Rog as an excellent teacher and mentor. “His teaching and mentoring style is welcoming and inclusive. He manages to get undergraduate students excited about genetics. My undergrad mentee told me his dream is to become a genetics professor because of Rog’s influence,” says Kursel. Rog is also deeply involved in the graduate program, where he serves as an advisor on the graduate program committee.

Another of Rog’s passions is to improve science communication. As far as his research is concerned, he believes that the tools to communicate the dynamic chromosome movement are limited. “Anything you draw will look like two separate things and will not convey the dynamic nature. Static images also fail to convey that the molecules are constantly rearranging during sexual reproduction,” he explains. In coordination with Janet Iwasa, a molecular animator and Assistant Professor in the Department of Biochemistry at the University of Utah, Rog organized a conference bringing together scientists and experts in visualization technologies, such as animators, illustrators, and developers to build virtual reality platforms that communicate his work on dynamic chromosome biology. He also created an intensive fellowship writing course for graduate students to address an unmet need in formal training for science writing.

Join us in congratulating Ofer Rog, who received the Genetics Society of America Early Career Medal at The Allied Genetics Conference 2024 in Metro Washington, DC.

2024 GSA Awards Seminar Series

In a recent seminar, Ofer Rog joined us to discuss two unpublished stories from his lab–the first documenting the unexpected de-mixing of sister chromatids during meiotic prophase and the mechanisms that mediate it, and the second describing a new genomic technique his lab developed to characterize large-scale chromatin organization and its application to meiotic chromosomes. Watch the recording here!

Sejal Davla, PhD, is a neuroscientist, science writer, and data scientist with expertise in research in a variety of life sciences. She has more than a decade of experience studying the brain by using cutting-edge methodologies in microscopy, molecular biology, genetics, and biochemistry, and is a motivated storyteller and science communicator.

“How do genes control physical, behavioral, and disease traits?” is a perennial question for geneticist Elaine Ostrander, Chief and Distinguished Senior Investigator of the Cancer Genetics and Comparative Genomics Branch at the National Human Genome Research Institute of the National Institutes of Health and Section Head of Comparative Genetics. Ostrander, who is known for her seminal discoveries in trait heritability in dogs and humans, tracked the history of dog breeds to address questions in morphology, behavior, and disease variation. She also mapped important cancer genes in canines and humans, advancing the knowledge of how complex diseases are inherited. 

Developing a canine genetic model from scratch

Ostrander started her scientific journey by investigating the relationship between the DNA structure and transcription in yeast during her PhD and postdoctoral years. Learning about the discovery of microsatellites steered her into mammalian research. “It became immediately clear that microsatellites were polymorphic in a population that they were useful for studying variation, but they were also stable enough to track inheritance of sections of DNA within a family. Suddenly, it became possible to make a genetic map of any mammal you cared about,” she recalls.

For Ostrander and Jasper Rine, that choice of mammal was a dog. While other scientists studying genetics were mapping genes in flies, worms, yeast, and humans, Ostrander, working in Jasper Rine’s research group at the University of California, Berkeley, began to construct a genetic map of the dog genome, with a long-term goal of using the map to find genes that distinguish breed appearance and behavior as well as genes associated with disease susceptibility. Continuing this work in her own research group at Fred Hutchinson Cancer Center, Ostrander created the first linkage maps in dogs in the early 90s. A decade later, her foundational work snowballed into a modern canine genetics project establishing dogs as a genetic model system. “Ostrander’s work built the stage and collected, in collaboration with several institutions, the first whole genome sequence of a domestic dog, the Boxer, in 2005. The subsequent decade was populated by an explosion of publications and genome developments led by her research group and collaborators,” says Bridgett vonHoldt, Associate Professor of Ecology and Evolutionary Biology at Princeton University and a long-time collaborator of Ostrander.

According to Leonid Kruglyak, Professor of Human Genetics and Biological Chemistry at the University of California, Los Angeles and Howard Hughes Medical Institute Investigator who nominated Ostrander for this honor, “Ostrander is without a doubt the leader in the field of canine genetics and genomics.” Leading an international consortium, Ostrander helped generate a global public repository consisting of genomes from 2,000 individual canids—including 1,611 dogs of known breeds (321 breeds), 309 village dogs, 63 wolves, and 4 coyotes—to address questions surrounding domestication, behavior, morphology, and disease susceptibility.

“Dogs were an obvious choice because the dog breed structure makes it easier to find genes responsible for traits. To be a member of a breed, parents and grandparents must be members of the same breed, making each breed a closed population,” explains Ostrander. Tapping into breed structure, where breed appearance and behavior remain intact generation after generation, Ostrander’s group identified genes responsible for the remarkable differences in size and shape between breeds. Her work showed that a single allele of IGF-1 is a major determinant of size in small breeds and that coat variation is determined by variants in just three genes. By identifying the time when variants first showed up in ancient DNA, her work takes a holistic view of morphology and behavior across different canid species.

Studying man’s best friend to understand humans

In addition to genes in dogs, Ostrander extensively studied human cancer genes in her laboratory at the Fred Hutchinson Cancer Research Center, focusing on human breast and prostate cancer. Her group was one of the first to describe a role for BRCA1 and BRCA2 mutations in women from the general population at risk for breast and ovarian cancer. Her expertise in dog genetics dovetailed well with this work, as she ended up discovering cancer-causing DNA variants in both humans and dogs. “Most things that dogs get, humans also get—they get the same cancers and diabetes; they also get many of the same neuromuscular, kidney and heart diseases. Some breeds are at an extraordinary risk for certain types of cancer. For instance, a Scottish Terrier is at 20-fold higher risk of getting bladder cancer than any mixed breed dog. Therefore, the underlying genetics must be really strong and profound,” explains Ostrander.

In an effort to explore the history between the dog and cancer genomes, her group used a multi-omics approach that was largely unexplored in the canine model to create the largest catalog of canine whole-genome, transcriptome, and chromatin immunoprecipitation sequencing. Such resources allow scientists today to identify common cancer-causing alleles in dog breeds and link them to human malignancies. For example, Ostrander identified two regions in the canine genome that explain a risk for developing a lethal histiocytic sarcoma, which also occurs in humans. By understanding genes in these risk regions in cancer-related pathways, her work empowered new diagnostics and therapeutic strategies for human cancers.

Ostrander’s group also studies aging and survival-related genes. “Big dogs do not live as long as little dogs. We would like to know why that happens,” she says. To solve this puzzle, Ostrander collaborated with international researchers looking for dog samples in the most unlikely places. “We are studying DNA samples from over 400 dogs, sampled by collaborators, from the exclusion zone around the Chernobyl nuclear power plant. We are looking for changes in DNA that dogs have accumulated over 15 generations which allows them to survive in this radioactive environment,” says Ostrander.  

A champion in all walks of life

Ostrander has contributed greatly to the scientific community through making her cutting-edge research in dog genetics accessible to the general public. A big proponent of community outreach, she takes pride in regularly engaging with dog groups, breed clubs, professional dog trainers’ associations, and families to help answer questions about behavior and diseases.

In addition to being a pioneer in science, Ostrander is also at the top of her game in powerlifting. She is a nationally ranked powerlifter, competing as a Masters lifter for five years. With a growing accumulation of first- and second-place medals, Ostrander looks forward to a time when she trains Masters lifters herself.  

Join us in congratulating Elaine Ostrander, who received the Edward Novitski Prize at The Allied Genetics Conference 2024 in Metro Washington, DC.

2024 GSA Awards Seminar Series

In a recent seminar, Elaine Ostrander discussed how domestic dogs are among the most variable mammalian land-based species on earth and the genetic underpinnings of that variation, including breed-associated morphology, behavior, and disease susceptibility. Watch the recording here.

Sejal Davla, PhD, is a neuroscientist, science writer, and data scientist with expertise in research in a variety of life sciences. She has more than a decade of experience studying the brain by using cutting-edge methodologies in microscopy, molecular biology, genetics, and biochemistry, and is a motivated storyteller and science communicator.

Build-a-Genome (BAG) course 

Boeke studied transposable elements in yeast and mammalian cells. Along the way, he decided to synthesize transposon DNA from scratch. “I was impressed with the power of being able to do that, which led me to synthesize first a synthetic chromosome arm and eventually the entire yeast genome with people around the world,” he describes. Using this first synthetic eukaryotic genome project, Boeke developed a unique laboratory component for his class that allowed students to contribute to this mammoth research endeavor.

“We built the genome from scratch, starting with oligonucleotides to entire genomes worth of synthetic chromosomes, piece by piece. In the early phases, we involved a lot of undergraduate students,” he explains. For Boeke, the course had two essential components. “One was to use the manpower needed to build such an enormous genome. The other was that it’s a fantastic way to teach molecular biology and genetics to undergraduate students, for whom it was new. They were doing original research as part of a course, learning about how to do a PCR reaction,” he shares. Because students were synthesizing genome fragments that were never created before, they faced several setbacks and performed extensive troubleshooting. This integral component of the course provided an authentic research experience to students.

Eventually, the course evolved as the technologies advanced. In the early years, students would generate 750 base pairs (bp) of synthetic fragments using PCR reactions on overlapping oligos. They would run gels to get clean bands and regularly present their observations in lab meetings. However, as the cost of synthesizing synthetic DNA fragments rapidly decreased, the course shifted from fundamental molecular biology in E. coli to yeast genetics. “The students started assembling medium-sized DNA pieces into bigger pieces using homologous recombination in yeast. After successfully running the course for 20 years and using work from undergraduate students, they are now helping combine sixteen fully man-made synthetic chromosomes and put them into a single strain,” says Boeke.

“Running the course wasn’t always easy,” describes Patrick Cai, Professor of Synthetic Genomics at the Manchester Institute of Biotechnology and former course instructor. “Boeke was running the course on a very limited budget, so we did a lot of work ourselves. One night, he drove his pickup truck and two of us moved all the chairs across the campus to a new course location. He was that dedicated and serious about the course,” says Cai.

With Boeke’s steadfast commitment and exceptional planning, the course eventually culminated in a global research and teaching consortium. Researchers from across the globe came to Boeke’s laboratory and learned teaching modules to build their parallel courses. “For example, Yingjin Yuan, Professor of Biochemical Engineering at Tianjin University, came to us and we helped him set up this course in China. He and colleagues focused on turning the course into a production machine and developed a landmark project by finishing one whole synthetic yeast chromosome in just a year,” says Boeke.

Teaching how to teach

Boeke involved his graduate students and postdoctoral researchers in teaching the course. According to Lisa Scheifele, Associate Professor in the Department of Biology at Loyola University Maryland, “The number of postdoctoral fellows and graduate students who have been empowered to learn the art of teaching, mentoring students, and developing course structure and content is notable and impressive.” She adds, “Boeke has been incredibly supportive of trainees who wanted to include a significant teaching aspect in their future careers. The Build-a-Genome course was my first teaching experience that ‘lit the fire’ for a future career where I’ve been able to blend teaching and cutting-edge research as we have done in Build-a-Genome.” Plus, the fact that this course inspired several of Boeke’s trainees in pivoting to a teaching career is something he’s quite proud of.

Harnessing the power of designer yeast

The synthetic yeast genome built through this innovative laboratory course offered a major paradigm shift in genetics and biotechnology, showcasing how to design and assemble synthetic DNA at scale. These synthetic chromosomes further facilitate testing genome fundamentals traditionally difficult to dissect in laboratory yeast strains. “Our knowledge about yeast genetics is largely based on our observation of the natural yeast genomes, which sometimes can be difficult to study. The synthetic yeast genome allows us to engineer the genomes to address societal challenges,” explains Cai. For example, Boeke made a bold choice to remove all the tRNA genes from the synthetic chromosomes and put them all on a new chromosome, allowing researchers to engineer it independently of all the other chromosomes. Now, Cai is testing yeast strains with tRNAs adapted to human codon usage to better express human proteins that can in turn be used in therapeutic applications to increase product yield.

Join us in congratulating Jef Boeke, who received the Elizabeth W. Jones Award for Excellence in Education, on behalf of Build-A-Genome, at The Allied Genetics Conference 2024 in Metro Washington, DC. And congratulations to the Build-a-Genome team whose members include Jessica Dymond of In-Q-Tel; Lisa Z. Scheifele of Loyola University Maryland; Eric Cooper of Hartwick College; Robert Newman of North Carolina Agricultural and Technical State University; Franziska Sandmeier of Colorado State University, Pueblo; Yu (Jeremy) Zhao of NYU Langone Health; Stephanie Lauer of St. Thomas Aquinas College; and Raquel Ordoñez of NYU Langone Health.

2024 GSA Awards Seminar Series

In a recent seminar, Jef Boeke, who received this award on behalf of Build-a-Genome, described how the course teaches students fundamental principles of genetics and how to perform, interpret, and troubleshoot an experiment when the outcome is unknown. He also touched on the history of the course and the resultant Network of Build-a-Genome courses, how it has affected students and instructors, and the course’s impact on the overarching International Sc2.0 project. Watch the recording here.

Sejal Davla, PhD, is a neuroscientist, science writer, and data scientist with expertise in research in a variety of life sciences. She has more than a decade of experience studying the brain by using cutting-edge methodologies in microscopy, molecular biology, genetics, and biochemistry, and is a motivated storyteller and science communicator.

Just like Thomas Hunt Morgan, Paul Sternberg’s scientific legacy dominates many fields of biology, including embryology, evolution, genetics, neuroscience, and systems biology. Sternberg, who is Professor of Biology at California Institute of Technology and Investigator Emeriti at Howard Hughes Medical Institute, studied parasitic nematode worms to make important discoveries in comparative development across different worm species and their behavior. 

Unraveling fundamentals of worm biology

During his undergraduate studies, Sternberg wasn’t particularly interested in science, but classes in quantum mechanics and microbiology attracted him to logic and exploration. He enrolled in mathematics and economics with the hope of applying relevant lessons to complex systems, but “…then I realized you can’t really do experiments in economics. I thought there is an interesting complexity in biology too, so I chose biology,” says Sternberg. As an undergraduate, Sternberg was looking at cell cycle control in slime molds. “By the time I was a graduate student, the worm appealed to me, and I wanted to understand everything about the organism. That is the goal,” he shares enthusiastically.

During his PhD, Sternberg contributed to groundbreaking work in the evolution of cellular lineages and developmental mechanisms for the induction and patterning of worm vulva. “When he was a student, his interest in the evolution of development was way ahead of his time. In the cell lineage paper by John Sulston and colleagues that reported the first comprehensive embryonic lineage analysis in 1983, they cited papers from Sternberg as a student in the Horvitz laboratory, identifying evolutionary changes in nematode cell lineages and cell fate. While Horvitz and Sulston received the Nobel Prize for their lineage work, Sternberg was also dissecting lineages in another genus and investigating how lineages would evolve. In that sense, he was prescient and visionary,” says Ryan Baugh who did his Postdoctoral training with Sternberg and is now a Professor of Biology at Duke University. 

Continuing the vulva development paradigm in his independent research group, Sternberg cloned and mapped numerous receptors and ligands, determining their functions in the signal transduction pathway. This pioneering work is taught today in introductory genetics and developmental biology courses to illustrate intercellular signaling, transcriptional regulation, and genetic epistasis mechanisms in coordinated organ development. Additionally, his students showed the importance of vulva development genes in the male mating structure called hook formation, further demonstrating conserved gene function in different organ patterning.

Sternberg also solved the mystery of the chemotaxis of males to the hermaphrodites, which many believed had no specificity. “People would say, male worms mate with chunks of agar. We looked at different species and found specificity. Hermaphrodites in a conditioned media would give pheromone signals that the males would respond to,” explains Sternberg. He collaborated with chemists to assess the chemical nature of purified mating attractants and discovered nematode-specific chemicals called ascarosides. Over the years, he made discoveries surrounding how males sensed ascarosides and nutrients in their environment to determine whether they should reproduce or wait. Using transcriptomics and CRISPR to knock out multiple genes, he continues to identify neuronal signaling in the pheromone sensing process.

In his quest to understand the worm, Sternberg studied multiple nematode species. His major interest is identifying lineage differences in species different from C. elegans, a commonly studied worm species. “We collected a lot of nematodes from soil and worked with a professional taxonomist, who figured out whether they are a diverse set of worms. Over the years, my students performed numerous comparative developmental analyses and started their research programs,” says Sternberg. 

Behavioral genetics is another field where Sternberg has made a huge impact. “What is the most complicated thing the worm does in the neuroscience sphere? The male mating behavior seemed pretty complicated to me,” shares Sternberg on how he focused his research. Sternberg’s student ablated each male-specific neuron using the knowledge from lineage maps and identified neuron-specific mating behavior defects. Observations from male mating behavior led him to investigate complex behavior like sleep, where he discovered several neuropeptides and signaling molecules controlling sleep in worms. To further strengthen the idea of sleep in invertebrate model organisms, Sternberg says, “I thought to push the defensive perimeter out in phylogenetic evolution in some primitive organisms. We studied jellyfish and found sleep-like states in them.”

According to Baugh, “It is really impressive that he went into neuroscience and behavior in addition to the evolution and development and trained important leaders in that field. I am seeing whole swaths of biology that are monumental as most people would hope to accomplish in their careers. He has just done it many times over.”

A community builder and a problem solver

Sternberg is also a visionary when it comes to building a scientific community and solving problems related to resource sharing and knowledge dissemination as well as developing new tools. “He sees a problem, and he fixes it,” says Maureen Barr, Professor in the Department of Genetics at Rutgers University, who did her postdoctoral research with Sternberg. “The C. elegans genome database was difficult and frustrating to navigate. Sternberg wanted to fix it, so he made WormBase. There are just too many papers – it’s not humanly possible to read them all, so he made Textpresso, which provides detailed information based on a few keywords. There are negative results in science that others might be interested in knowing, so he created microPublication where researchers can publish brief, novel findings and negative results that may not fit a traditional research article,” says Barr. Sternberg actively runs and supports these irreplaceable tools that make science accessible.  

Join us in congratulating Paul Sternberg, who received the Thomas Hunt Morgan Medal at The Allied Genetics Conference 2024 in Metro Washington, DC.

2024 GSA Awards Seminar Series

On July 30, at 1:00 p.m. EDT, Paul Sternberg will join us to describe how C. elegans as an extensively-studied research organism holds out the promise of achieving comprehensive understanding of an organism. He will also discuss the status of our knowledge of how a genome sequence specifies the properties of an organism in the context of state-of-the-art technology and cool biology. Save the date and register here!

Sejal Davla, PhD, is a neuroscientist, science writer, and data scientist with expertise in research in a variety of life sciences. She has more than a decade of experience studying the brain by using cutting-edge methodologies in microscopy, molecular biology, genetics, and biochemistry, and is a motivated storyteller and science communicator.

Deborah Andrew’s journey from a first-generation college student to a leader in fruit fly genetics is nothing short of inspiring. She began her undergraduate studies in freshwater ecology; during that time, she took a genetics class taught by fruit fly geneticist David Kuhn that changed the course of her career. She worked in fruit fly genetics laboratories throughout her academic training to understand the role of homeotic genes in organ formation. Andrew, now the Bayard Halsted Professor of Cell Biology at the Johns Hopkins University School of Medicine, is still dedicated to studying organogenesis, particularly in uncovering genetic mechanisms governing tubular structures in Drosophila.

Mapping tubular structures from birth to morphogenesis

“I have always been interested in the questions about how a relatively nondescript fertilized egg turns into the multitude of specialized cell types found in the mature organism. Interested in organ formation, I began addressing the following questions: How is organ fate specified? How do organs specialize? How do they achieve their normal morphologies?” explains Andrew. Harnessing the power of genetic tractability in Drosophila, her pioneering work addressed fundamental mysteries in the salivary gland (digestive system) and trachea (respiratory system) development.

Andrew’s group made considerable strides toward understanding how an organ develops in its primordial state and achieves a final functional morphology by identifying the major transcription factors that control these processes at different stages of embryonic development. The major regulators of organ specification and function are known for only a small handful of organs in even fewer organisms. Remarkably, Andrew’s work identified major regulatory genes for salivary gland and trachea development and their interactions with downstream target genes. 

The salivary gland contains specialized cells with very high levels of secretion. The discovery of a conserved bZip-family transcription factor CrebA as the major regulator of increased secretory capacity is one of the most important findings from Andrew’s research group. “CrebA upregulates nearly all secretory pathway component genes, including genes encoding the protein components of the ER, Golgi, and secretory vesicles, as well as the genes that encode the proteins that transport nascent polypeptides to secretory organelles. This single transcription factor—CrebA—upregulates all of those,” emphasizes Andrew.

From fundamental biology to a direct impact on human health

Discovering conserved positive regulators of tube formation and secretion processes, Andrew’s work showed tremendous potential in developing artificial salivary glands and conferring secretory abilities to non-secretory cells. Her lab showed that each of the five human orthologues of CrebA could also induce the expression of secretory pathway component genes in fly embryos, highlighting the functional conservation of this gene family. Indeed, by expressing the closest mammalian ortholog of CrebA in HeLa cells, her group showed a similar upregulation in human secretory pathway gene expression. Such strategies could help ramp up the production of secretory products in biotherapeutic applications.

Andrew used her expertise in the Drosophila salivary gland to study the orthologous structure in Anopheles mosquitoes. The malaria-causing parasite Plasmodium migrates to the salivary gland ready to be injected into the vertebrate host at the time of feeding. Her group identified another transcription factor Sage that expresses only in the salivary gland. When knocked out from the Drosophila salivary gland cells, cells die massively via apoptosis. Now, her lab is using CRISPR technology to knockdown Sage from mosquito salivary glands in the hope of achieving cell death. “Moreover, Andrew has shown that the polarized architecture of the salivary gland acts as a natural barrier for parasite transmission. This line of investigation is likely to generate new targets for transmission-blocking strategies,” says Geraldine Seydoux, Professor of Molecular Biology and Genetics at Johns Hopkins University and long-time colleague and collaborator of Andrew.

A beloved mentor and community leader

Throughout her career at the Johns Hopkins School of Medicine, Andrew considered herself privileged to work with young scientists, and her trainees returned the feeling. Andrew’s former trainee Caitlin Hanlon described her as an incredible mentor who always showed confidence in what her trainees could achieve. “Her dedication to helping train people and showing up for them created a wonderful and meaningful work culture not just in the laboratory but also in the department,” says Hanlon, who is now an Associate Professor at Quinnipiac University. Andrew also contributed to teaching efforts at Johns Hopkins. She dedicated countless hours teaching medical and graduate students the fundamentals of cell biology and physiology, keenly elucidating how things really work at the basic level in any cell. 

In addition to being a leader in her research field, Andrew generously offered her time and expertise to build fly genetics and development biology communities. She served as a representative to the Drosophila Board (“Fly Board”) from 1996 to 1999, as treasurer from 2013 to 2016, and president in 2017. She has organized major conferences over the years, including the Annual Drosophila Research Conference, the Santa Cruz Developmental Biology Meeting, and a Gordon Research Conference. She has been a long-term member of the Drosophila Genetics Resource Center Advisory Board.

Beyond her exemplary research and community work, Andrew is a fierce advocate of fundamental research and the fruit fly model system. “I would like more people to enter the Drosophila field. While we can do so many things in other systems, such as humans and mice, I strongly believe you get more bang for your buck in fly research,” emphasizes Andrew for scientists in training, encouraging them with a firm belief that what can be discovered in flies cannot easily be discovered anywhere else.

Join us in congratulating Deborah Andrew, who received the George W. Beadle Award at The Allied Genetics Conference 2024 in Metro Washington, DC.

2024 GSA Awards Seminar Series

In the first installment of the 2024 GSA Awards seminar series, Deborah Andrew described her lab’s findings on how the Drosophila salivary gland is first specified and maintained, and how early and continuously expressed transcription factors control both secretory capacity and specificity. She also shared recent efforts using genome-wide approaches to discover how functional enhancers of downstream target genes are organized. Watch the recording here!

Sejal Davla, PhD, is a neuroscientist, science writer, and data scientist with expertise in research in a variety of life sciences. She has more than a decade of experience studying the brain by using cutting-edge methodologies in microscopy, molecular biology, genetics, and biochemistry, and is a motivated storyteller and science communicator.

As announced earlier this year, GSA’s Board of Directors launched an audit to review the five major awards conferred by the Society: the Edward Novitski Prize, the Elizabeth W. Jones Award for Excellence in Education, the Genetics Society of America Medal, the George W. Beadle Award, and the Thomas Hunt Morgan Medal.

The central goal of the audit was answering a key question: Do our current awards exemplify the GSA community’s core values? To answer this question, the audit assessed three essential components of the awards program: 1) the nomination process, 2) the review process, and 3) the eligibility and criteria used to confer each of the five awards. The Awards Audit Task Force discussed these components, looking for sources of bias, unintended barriers, and ways to diversify the nominees—and thus the award winners. The Task Force also met with focus groups to bring in a wider variety of opinions and points of view.

Based on the audit, the Task Force proposes the following changes to the GSA Awards process:

Nomination Process

Previously, two letters of support were required: an initial nomination letter, including a description of the nominee’s merit for the particular award and a letter of support from a secondary nominator. The letter of support could be co-signed by as many individuals as were willing. Nominees were then approached to provide an up-to-date CV. 

The audit identified a number of potential barriers and sources of bias within the existing nomination process. We have revamped the process in the following ways:

First, the Task Force recommends moving to a single nomination letter with a supporting questionnaire specific to the particular award. This questionnaire will help standardize the information collected on each nominee; nominees will help their nominators complete the questionnaire. The nominee will be contacted to provide an NIH-style biosketch (no more than five pages) and a brief lived experience statement. This statement allows nominees to volunteer information about their career paths, including potential barriers that they have faced and/or overcome, without requiring disclosure; it also lets nominees present their research/mentoring/teaching/DEI philosophies for consideration in addition to their biosketch. We invite self-nominations; self-nominators should reach out to a colleague to co-sign their nomination.

Second, GSA will create a GSA Awards Nomination Committee comprising members from the community representing the richness and diversity of the society. This subcommittee will proactively invite nominations from various departments, schools, model organism boards, and other relevant groups. The goal is to broaden the pool of nominees from a wide variety of backgrounds. 

Finally, as part of GSA’s efforts to improve equity and inclusion, we will collect nominee demographic data on a volunteer basis to help us gauge our progress. We strongly encourage nominees to answer demographic questions; their answers will not affect the committee’s decision-making process and will be kept confidential.

After five years, this new nomination process will be reviewed by the Board to assess the degree of success.

Review Process

The GSA Awards Committee oversees the review process. Members of the Awards Committee are appointed to a three-year term by the GSA President and Board of Directors. The committee reviews all nomination materials and identifies three candidates for each award. The three candidates from each award are submitted to the Board of Directors for consideration, and the Board votes to select the awardee.

The audit found that the review process did not need significant changes. 

Award Descriptions and Criteria

The audit revealed a measure of confusion about the potential overlap in criteria for some awards. Specifically, the Task Force noted that the Thomas Hunt Morgan Medal and the Genetics Society of America Medal were often both used as lifetime achievement awards. The Beadle Award and Novitski Prize were both used to recognize contributions via community-resource/reagent creation. Additionally, the lack of recognition for early- and mid-career scientists was obvious. 

To best address these deficits, the criteria for each award will be refined as follows to best reflect GSA’s ethos and the goal of each award. Notably, the GSA Medal will now be explicitly defined as a mid-career award, and a new Early Career Medal will be added to the slate.

• The Morgan Medal will remain a lifetime recognition of an individual based on their contributions to the field of genetics, which include mentoring, community service and research portfolio.
• The GSA Medal will now be awarded at mid-career to an individual with seven to 15 years of experience in their independent research career at the time of nomination. The awardee will be recognized for their research excellence, mentoring, community engagement, and other related activities.
• A new GSA Early Career Medal will be awarded to an early-career individual within the first seven years of their independent research career at the time of nomination. The awardee will be recognized for their research excellence, mentoring, community engagement, and other related activities.
• The Novitski Prize will recognize creativity at all career stages, including graduate students, postdoctoral fellows, and faculty. The nomination must clearly state the creative effort being recognized, and up to two individuals may jointly receive the prize.
• The Jones Award will continue to recognize the contribution to education from K-12 onwards. Individuals and teams can be nominated.
• The Beadle Award recognizes an individual’s service to the community. Beadle nominees should have clear and demonstrable community engagement, service, and leadership beyond research endeavors. GSA will particularly invite nominations of individuals who have worked to make the community more inclusive and diverse. Individuals and teams can be nominated.

Timeline

To give us time to enact these changes and ensure process updates, the Task Force recommended extending the awards cycle timeline. The Board of Directors discussed this recommendation and agreed that GSA will not announce any awards for 2022. Instead, applications will be solicited early in 2023 to be awarded in summer of the same year.

Ever since Charles Darwin proposed the idea of natural selection in 1858, biologists have been pondering exactly how selection works, somehow driving the evolution from single-celled life to the wide array of complex vertebrates that now populate the planet. As advances in technology have enabled genomic mapping at increasingly finer resolution, the questions have only deepened. How could natural selection, “survival of the fittest,” allow for so much duplication and seemingly unnecessary stretches of DNA seen in vertebrate genomes? Why haven’t the forces of evolution created a lean, sleek genomic masterpiece?

By combining population genetics with quantitative genetics, Michael Lynch has made remarkable progress toward answering these questions. He’s shown that natural selection is just one of several mechanisms driving evolution, and that much genomic complexity arose “passively” through an accumulation of random changes that nature couldn’t eradicate. His ideas have ruffled more than a few feathers in the evolutionary biology world, but his paper on genetic subfunctionalization, or how duplicated genes acquire new functions, became one of the most-cited GENETICS papers of all time. He authored the seminal text, Origins of Genome Architecture, and now he’s working to found a new field, evolutionary cell biology.

“Michael Lynch is a pretty amazing individual,” said Chris Amemiya of UC Merced. “He’s been a real driver of a lot of science in this country.”

For his accomplishments, Lynch has been awarded the 2022 Thomas Hunt Morgan Medal for lifetime achievement in the field of genetics from the Genetics Society of America.

Comparing proteins, comparing genomes

Lynch started out as an ecologist, but after switching into population genetics and quantitative genetics, he became interested in applying the concepts of these fields to natural populations. “It started out at a pretty crude level,” he recalled, before the widespread availability of DNA sequencing. To identify genetic differences, the team looked for differences in proteins. “We were doing what were called allozyme gels, for protein variants, which was pretty neat. It gave us a first glimpse of variation. But it was a real art form.”

The rise of fast, cheap DNA sequencing enabled scientists to interrogate genomes at the individual level at unimaginable depth. “We could go beyond just speculating,” Lynch says. “I started developing models for understanding how genome complexity evolves, particularly how we can passively evolve in a domain where we have more and more complex genomes, even though that’s not pushed forward by natural selection.”

The common understanding of Darwinian evolution is roughly as follows: random mutations lead to variation within a population, and occasionally a mutation will arise that confers its bearer with a reproductive advantage. Natural selection is the process by which these beneficial mutations outcompete their less-advantageous counterparts. Over millions of years, this process leads to species becoming exquisitely adapted to their particular ecological niches. As so often happens in biology, however, this explanation omits quite a bit.

Genome complexity can arise passively, without selection

Some mutations are mild enough that selection pressure can’t stop them from accumulating, Lynch explains. “The messy genomes of big clunky vertebrates and land plants are not due to the fact that everything’s driven by refinements by natural selection,” he says. “It’s a consequence of the inability of selection to eliminate what would ordinarily be viewed as bad changes in the genome.” Introns are one example of this, he points out. For every additional base pair a chromosome accumulates, the organism has to spend more energy to maintain and replicate that lengthened genome, and yet the genomes of complex organisms are stuffed with sequences that never make it into a finished protein.

“One quite influential piece of work that came out of the very earliest days was our work on gene duplication,” Lynch says. In their groundbreaking paper, Lynch and graduate student Allan Force showed how mutations in different regulatory elements of duplicated genes allow both copies of the gene to be retained and, eventually, lead to divergent gene functions. This contradicted the prevailing idea that when a gene is duplicated, one copy eventually accumulates enough mutations that it either degenerates or, in rare cases, acquires a new function.

“This was 1998. We’d hardly had any genome sequences yet; that was just starting to happen,” Lynch said. “I think we were in the right place at the right time. Prior to that point, people knew genes were duplicating, but we had no idea how common it was.”

Lynch and Force realized that duplicate genes were far too common for every new duplicate to have acquired a completely new function. In their paper, they argued that if the original gene had multiple functions governed by different regulatory elements in different types of cells—for instance, the head and thorax of an insect—that modularity could allow the duplicate gene to diverge via mutations in the regulatory element. “What can happen is one loses its ability to be expressed in head, and the other gets complementary degenerative mutations, and it can’t be expressed in thorax,” said Lynch. “Nothing’s changed dramatically, biologically. But you’ve made a more complex organism.”

The Center for Mechanisms of Evolution

In 2017, Lynch moved to Arizona State University to launch the Biodesign Center for Mechanisms of Evolution. “We’re trying to grow a new center with six new faculty, plus me, all focused on trying to understand evolution at the cellular level,” Lynch says. “We’re trying to integrate biochemistry and biophysics into this mix as well, to come up with a comprehensive view of how cellular features evolve, or don’t evolve. What are the constraints—what prevents cells from going down a certain route?” 

Lynch calls evolutionary cell biology “the last missing link,” pointing out, “There’s an amazing field of cell biology; everything’s done in exquisite detail at the molecular level. But there’s no real evolutionary biology in cell biology.”

“This unique Center promises to diversify the field of evolutionary genetics into new avenues of inquiry,” write Bill Bradshaw and Chris Holzapfel, who nominated Lynch for the medal. “This diversification will lead not only to greater insight into the genetics of evolutionary processes, but also into medically important areas of genetic disorders. Under Lynch’s direction, the Center will produce a new generation of forward-looking geneticists firmly rooted in integrative and transformational research.”

Indeed, Lynch has long championed integrative research, says Amemiya. “He’s got his hand in a lot of things, not only in genetics, but also in developmental biology and ecology. Some of these principles, I think, have been percolating for a long time, and he was able to bring these kinds of ideas into the fore.” Lynch has served as president of multiple scientific societies, including the Society for the Study of Evolution, the American Genetic Association, the Society for Molecular Biology and Evolution, and, of course, the Genetics Society of America. “He’s been an amazing advocate for interdisciplinary science,” Amemiya says.

The Thomas Hunt Morgan Medal recognizes individual GSA members for lifetime achievement in the field of genetics. Recipients have made substantial contributions to genetics throughout their careers and have a strong history as a mentor to fellow geneticists.

Harmit Malik loves conflict—genetic conflict, that is. “I’m really interested in this idea that components of the same genome, or components of different genomes, are constantly doing battle with each other,” says Malik, who heads a lab at the Fred Hutchinson Cancer Research Center.

To understand genetic conflict, Malik focuses on the parts of the genome that are rapidly changing and evolving. By studying these tumultuous regions, Malik has made impactful discoveries, some of which have overturned the conventional wisdom in genetics that the most important elements of the genome are protected from rapid mutation.

For his contributions, Harmit Malik has been awarded the 2022 Edward Novitski Prize, which recognizes an extraordinary level of creativity and intellectual ingenuity in the solution of significant problems in genetics research.

Breaking evolution’s “speed limit”

Some genes evolve quickly, while others haven’t changed much throughout evolutionary history. Immune system genes, for instance, evolve fast to keep up with the relentless onslaught of different pathogens that they need to fight. For these genes, agility provides the organism with a selective advantage.

On the other hand, genes and proteins that are needed for fundamental cellular functions, like mitosis and meiosis, are expected to evolve much more slowly. Mutations in these genes would be detrimental to the organism’s fitness, presumably, and therefore kept to a minimum. It turns out that this isn’t always the case, however. During his postdoc, Malik made the astonishing discovery that centromeres, among the most essential structures in the cell, undergo unexpectedly rapid evolution.

Centromeres are the constricted regions that give chromosomes their “belted” appearance. They ensure that during cell division, both daughter cells inherit a full and correct set of chromosomes. Centromeric DNA is highly repetitive and does not encode genes, and centromeric histones are proteins that bind to these DNA repeats.

“Centromeric DNA, base pair for base pair, is actually one of the fastest evolving components of our genome,” he says, and centromeric proteins also showed a similarly rapid mutation rate. In fact, the researchers found that mutations arise in these regions faster than the random mutation rate would predict, implying an evolutionary pressure driving the rapid change. At the time, this was “a completely heretical idea, and one of the very first instances where an essential gene had been evolving under what we refer to as positive selection—this idea of faster than expected evolution,” Malik says.

Intrigued, he set out to find what was driving the rapid evolution of centromeric DNA and proteins. During the process of egg formation, four haploid daughter cells are formed, but only one gets selected to be the egg and the other three are destroyed. “We realized this actually introduced an incredible degree of competition as to which chromosomal variant was going to be inherited as the egg chromosome,” says Malik. This competition set the stage for “selfish” genetic variants to arise. A mutation in the centromeric DNA or proteins that increased the chance of being passed down to the egg would have a selective advantage.

Still, something didn’t add up. “It was actually against the best interests of the genome to have this selfish behavior,” says Malik. If centromeric DNA and proteins evolved together, each boosting the other’s inheritance rate, the selfish elements would quickly take over the population and reduce the genetic diversity of the offspring. “We then realized that, actually, they were probably working in conflict with each other,” Malik says. Malik and his postdoc mentor, Steve Henikoff, proposed the “centromere drive model,” which explains the rapid co-evolution of centromeric proteins and DNA as an effect of genetic conflict. While selfish centromeric DNA evolves to increase its chance of being passed down, the centromeric proteins were evolving to suppress this inequity and increase the random chance of any chromosome surviving to the next generation. “The entire centromere drive hypothesis came about to reconcile how something so fundamental to our cell division process could be subjected to the kind of innovation that we see in the host-pathogen interaction,” Malik explains.

Beyond the centromere

While Malik’s work has uncovered a tremendous amount about the evolution of the centromere, his interest in genetic conflicts has taken him into other uncharted research waters. “I think what most of us do is pick a topic that we’re interested in and then try to figure out how to address it,” says Sue Biggins, director of the Basic Sciences Division at Fred Hutchinson. “He has this opposite way of doing it, which is to say if something’s rapidly evolving, something super interesting is happening. He has this fascinating way of using rapid evolution to open up the questions for him. To me, that is the hallmark of someone really creative.”

For instance, Malik helped pioneer the field of paleovirology, studying the traces of viral genes left behind in host genomes over the course of evolution. Viruses are constantly mutating and evolving, and, correspondingly, defenses arise in the genomes of host organisms to combat them. By studying the DNA evidence of this evolutionary arms race, Malik and others hope to glean information about viral defense strategies that could someday be translated into antiviral therapies.

Malik’s creative enthusiasm makes him invaluable as a mentor and colleague. “Talking science with Harmit is invigorating and joyful, in part because of his openness, his authenticity, and his humility,” says Mia Levine of the University of Pennsylvania, who nominated Malik for the award. “He is a perpetual student, making these conversations feel like one of collaborative discovery. These interactions help you see the gold that you are sitting on and give you the confidence to tell the world about it.”

Creative ideas that challenge existing paradigms often run into resistance from the community, and it can take courage to swim against the current. Malik says that he draws on the fearlessness he learned from his mentors to convey that sense of daring to his early career scientists while also providing honest feedback. “My mentor was super supportive, and he really wanted us to not be afraid of being wrong,” he says. “I’m trying very hard to do the same thing. I want people to recognize that science is not a zero-sum game, that it’s actually possible for you to be successful and yet be a really good colleague.”

The Edward Novitski Prize recognizes an extraordinary level of creativity and intellectual ingenuity in the solution of significant problems in genetics research. The prize honors solid, significant, scientific experimental work—either a single experimental accomplishment or a body of work.

Becoming the president of a world-class university isn’t something that typically happens “by accident,” but that’s exactly how Shirley Tilghman describes it. “I did not intend to be a university president,” Tilghman says. “I probably had the steepest learning curve of any university president ever.”

In 2000, Tilghman was serving as founding director of the Lewis-Sigler Institute for Integrative Genomics at Princeton University. When Princeton’s then-president, Harold Shapiro, announced his departure, Tilghman joined the search committee to ensure that the next president would support the new genomics initiative. “I was going to protect my turf,” she says.

“I was on that committee for about six months. At one point, I left the committee early to teach, and when I came to the next meeting, the chair said, ‘The committee would like you to step down and to become a candidate.’ I thought they were out of their minds,” she recalls. “I think I said to them, ‘I can’t leave you people alone for a minute!’”

Still, Tilghman gave the idea careful consideration. “I decided I had probably done the best science I was going to do by that point,” she recalls. Considering a possible next chapter, she began to get excited about “the opportunity to make an institution that [she] adored—Princeton—better.” In June 2001, she was sworn in as Princeton’s first female president.

Tilghman’s body of research had, indeed, already secured her place in genetics textbooks. In addition, she served as a key advisor to the Human Genome Project, helping to steer the initiative through the capricious winds of government funding and forever transforming the field of genetics. For her outstanding contributions, Tilghman has been awarded the 2022 George W. Beadle Award from the Genetics Society of America, which recognizes individuals who have made outstanding contributions to the community of genetics researchers beyond an exemplary research career.

Genomic imprinting

As a postdoc, Tilghman helped develop a method of cloning mammalian genes. She went on to characterize the mouse beta-globin gene, uncovering a great deal about gene structure and “intervening sequences,” now called introns, that interrupt coding regions. As a faculty member at Princeton in the early 1990s, Tilghman and members of her lab studied a gene called H19, which was very highly expressed in the mouse embryo. The first odd thing they discovered was that the gene contained no open reading frame, indicating it could not encode a protein. “There was no other long noncoding RNA at the time, this was the first,” Tilghman recalls. “At that point, I was given very good advice from many colleagues who said [to] drop it like a hot potato.”

However, tantalized by the high expression levels in the embryo, Tilghman couldn’t let H19 go. Work by Marisa Bartolomei, a postdoc in the lab at the time, showed that H19 was only expressed from the maternal chromosome. “That’s when the floodgates opened,” Tilghman recalls.

H19 was located next to another imprinted gene, IGF2, which was only expressed from the paternal chromosome. This pair of genes provided the first evidence of imprinted gene clusters. Tilghman’s lab produced a number of papers characterizing the promoters and enhancers that lay between the two genes and describing the molecular mechanisms involved in imprinting, including chromatin organization and methylation as a key regulator of expression. Bartolomei, who now heads her own lab at the Perelman School of Medicine at the University of Pennsylvania, recalls that era of rapid discovery. “It was insanely exciting,” she says. “Shirley is definitely one of the more creative people who worked in the imprinting field.”

Human Genome Project and beyond

As one of the founding members of the National Advisory Council of the Human Genome Project, Tilghman helped define the public effort in sequencing the human genome. She advocated for sequencing the genomes of various model organisms in addition to the human genome, a move that conferred two key advantages. First, it allowed for small, incremental victories to maintain high enthusiasm for the project and keep funding flowing over the long timeframe required. Second, it expanded interest in the project and the perception of benefit to a wider range of scientists beyond just the handful studying human genetics. “A genome enthusiast,” she once said, “is a genome critic who just got a hit in their organism’s sequence database.”

Tilghman was influential in setting a precedent for data accessibility, starting with the mouse genome, says Tamara Caspary of Emory University, who was a graduate student in Tilghman’s lab. “It was really important to her that those data be publicly available,” Caspary says. “She very clearly highlighted that it needed to be community-driven, in terms of selecting what strains to be sequenced.” By actively involving the genetics community, Tilghman helped sustain a wide enthusiasm for the genome sequencing efforts that carried the project to its ultimate successes. Similarly, as a trustee of the Jackson Laboratory, she strongly supported establishing the Mouse Genome Informatics database. “It’s tremendous,” Caspary says. “The well just gets deeper with the data you can mine out of that website. She made that data accessible worldwide.”

Tilghman has been equally influential on the personal side of science, advocating for reform in the biomedical research pipeline. As ever-increasing numbers of trainees vie for limited resources, it becomes harder for science students and postdocs to envision a viable path to a research career. Tilghman has worked to address what she sees as systemic flaws in the process, including perverse incentives in research funding, problems with the peer review system and obstacles to new investigators obtaining federal grants.

Through all these accomplishments, Tilghman has served as an important role model for a generation of women in science. “She was incredibly fearless in going from one thing to another,” Bartolomei says. “She led by example. The key is that not only is she smart, she’s creative, she gives great talks—she’s the complete package. She taught me how to be a woman in science.”

The George W. Beadle Award honors individuals who have made outstanding contributions to the community of genetics researchers. GSA established the award in 1999 in honor of an outstanding scientist and a respected academic, administrator, and public servant—George W. Beadle (1903-1989).

Complex multicellular organisms have mastered the art of specialization; embryonic stem cells give rise to a multitude of different cell types that perform specific functions. Later, adult stem cells dedicated to specific tissues maintain and repair many organs in the body throughout life. Some specialized cell types, like skin, blood, lining of the intestine and colon, and sperm are continually replenished, each from their own dedicated adult stem cells. When such adult stem cells divide, they must not only spawn cells able to specialize into the correct cell type(s) but also produce new stem cells to maintain regenerative capacity.

Margaret “Minx” Fuller studies how male germ cells balance self-renewal versus differentiation to both maintain the stem cell population and continually produce sperm cells. Her research has helped uncover chemical signaling pathways and cellular mechanisms that underlie this process. By studying male germ cells within the context of their cellular neighborhood, Fuller showed that signals coming from surrounding cells coordinate with behavior of cytoskeleton components to induce the stem cells to divide asymmetrically. Studying how stem cells replicate and retain their ability to generate specialized cells could have important implications in cancer research as well as regenerative medicine.

For her achievements, Fuller has been awarded the 2022 Genetics Society of America Medal, which recognizes outstanding contributions in the field of genetics in the last 15 years.

“I don’t see many people who so seamlessly go back and forth between understanding of genetics and cell biology and developmental biology,” says Yukiko Yamashita, a Howard Hughes Medical Institute Investigator at MIT and former postdoc in Fuller’s lab. “Always there is clarity in her thinking, and that is her real contribution—that’s why so many people followed to adopt this model system.”

From physics to “APOG”

As an undergraduate, Fuller started out studying physics, but summer research in a biology laboratory changed her direction. “Maybe naively, I thought in physics you need a big machine between you and your questions—a neutrino detector or a synchrotron or whatever,” she says. A sophomore year biology class with laboratory revealed to her many fascinating unanswered questions, and her experiences at the bench the following summer sealed the bill. “I got hooked by the fact that in laboratory biology, you can ask and answer questions with your mind, some test tubes, and a water bath,” she says.

After graduation, she studied microbiology at MIT, where she worked on the protein-protein interactions that regulate virus capsid assembly. “The thing that was drilled into us was ‘APOG’—the awesome power of genetics,” Fuller recalls. Coming from physics, she was fascinated by how cells change shape and how protein-based machines build structures inside the cell. Researching what to study next for her postdoc, Fuller attended a conference on the cytoskeleton, where she was startled to discover that in the entire conference only two presentations, both posters, used genetics. “So I said, aha! This field needs genetics,” Fuller recalls. “I’m going to go do genetics on the cytoskeleton.”

During her postdoc at Indiana University, she studied proteins that interact with and regulate the microtubule cytoskeleton in spermatocytes, the cells that give rise to sperm cells. Working with mutants that effect spermatogenesis, Fuller realized that here was a perfect system to apply forward genetic strategies to investigate the questions that had caught her interest as an undergraduate and postdoc: How do cells change shape?  How does the developmental program add layers of regulation on fundamental cellular processes like cell division, transcription and mRNA processing to specify specialized cell types. When she set up her own lab, Fuller shifted to studying spermatogenesis, the process by which stem cells give rise to specialized sperm cells, in its own right. While a lot of labs were working on oogenesis and embryonic development, only a few at the time were studying spermatogenesis.

“She realized the overarching fundamental principles you could learn from studying a tissue where there are stem cells present that continue to divide throughout the whole adult lifespan,” says Julie Brill of the Hospital for Sick Children and University of Toronto, another of Fuller’s former postdocs. “She wasn’t the only one to develop the testis as a model, but Minx is just such a fabulous speaker that she also really brought people into the system.” As an example, Brill says, Fuller organized a “testis workshop” during the Annual Drosophila Research Conference, which helped create a community among researchers who might otherwise see themselves as competitors. “We all met each other and learned what everybody else was doing,” Brill says. “She’s so good at organizing and inspiring others around her.”

Pre-programmed versus environmental

Fuller’s work shed light on the question of whether the daughter cell fates were determined by pre-programming within the stem cell or by chemical signals coming from the “niche,” the environment outside the cell. “One of the major ideas in the field was that there was a niche, a local microenvironment that instructed the stem cells to maintain stem cell identity,” she says. This idea hadn’t been proven, because the standard procedure at the time was to isolate, sort, and transplant cells before evaluating their stem cell potential. “Well, you can’t study the role of the microenvironment if the first thing you do is take the cells out!” Fuller says. “I realized, I have a great system in my hands in my lab for studying the role of the microenvironment in stem cell biology, right here in the fly testis.”

In addition to signals from the microenvironment, Fuller’s work showed that stem cells also have internal mechanisms that bring about asymmetric cell division. The centriole is a microtubule-based structure that organizes the mitotic spindle, and when the cell divides, the two centrioles migrate to opposite poles. By marking the oldest centriole, Yamashita while in Fuller’s lab discovered that the older centriole stays anchored in the stem cell, while the cell that inherits the younger centriole goes on to become differentiated. “This whole mechanism of orienting the spindle and asymmetric division—I think that has been most impactful outside my immediate field,” Fuller says. Now, people studying other types of adult stem cells also look for whether or not the cells undergo asymmetric division, she says, partly inspired by the observations from the testis. Moving down the differentiation lineage, Fuller’s laboratory is now focusing on uncovering the mechanisms that regulate the switch from precursor cell proliferation to turning on expression of the correct cell type specific gene expression program.

Most recently, Fuller contributed to the Fly Cell Atlas project, an ambitious effort to catalog the gene expression profiles of all the cells in Drosophila. “It was during COVID, so we had a big Zoom jamboree of maybe 12 labs that contributed to that paper,” Fuller says. “It’s been a vehicle for open communication among labs that could have been competing, but we’re collaborating and it’s just so much fun.”

Over the years, Fuller says she has gotten great joy from seeing all the projects her trainees have been able to take with them when they leave to start their own labs. “The most gratifying thing to me is that a group of my former postdocs and students got together and wrote a nomination letter,” Fuller says. “I think my most important contribution to science has been all these fantastic people who are now doing their own science.”

The Genetics Society of America Medal honors an individual member of the Society for outstanding contributions to the field of genetics in the last 15 years. GSA established the Medal in 1981 to recognize members who exemplify the ingenuity of the GSA membership through elegant and highly meaningful contributions to modern genetics.