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.

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.