The unassuming fruit fly has paved the way for another big scientific win: on October 2nd, the Nobel Assembly awarded the 2017 Nobel Prize in Physiology or Medicine to Jeffrey C. Hall, Michael Rosbash, and Michael W. Young for their discoveries of the molecular mechanisms behind circadian rhythms. These biologists have spent their careers studying how organisms build an internal clock that synchronizes their biology and behavior to the day-night cycle.

Like many important discoveries about how life works, this story begins with one of biology’s most powerful tools: the forward genetic screen. In 1971, Seymour Benzer and Ron Konopka introduced random mutations into fruit flies and screened for mutants with a disrupted circadian rhythm. Benzer and Konopka identified these mutants by monitoring two phenotypes controlled by the circadian clock: what time of day the flies are most active in their enclosure (locomotor activity) and when they emerge from their pupal cases (eclosion). The scientists isolated three mutants with irregular rhythms, identified the single genomic locus associated with all three, and named it period (per).

Over a decade later, Hall and Rosbash, colleagues at Brandeis University, and Young, working at Rockefeller University, independently cloned the period gene. This discovery provided a crucial entry point for Hall, Rosbash, and Young to begin painstakingly putting together the molecular pieces of the circadian rhythm puzzle.

Rosbash and Hall found that levels of the protein product of the period gene (PER) oscillated throughout the day, peaking in the middle of the night. They also noted that per mRNA oscillated as well, though it peaked roughly six hours earlier than PER; this led them to suggest a negative feedback loop wherein the PER protein controls per mRNA expression. As the PER protein began to accumulate, they proposed, it started to put the brakes on its own synthesis.

PER protein was concentrated in the cell nucleus, which fit well with this theory—but PER wasn’t capable of translocating to the nucleus on its own, and its biochemical function was still unknown. It seemed apparent that per gene regulation was directly related to the circadian clock, but the mechanism was still shrouded in mystery.

Meanwhile, a few hours away in Manhattan, Young and his colleagues were identifying new circadian rhythm mutants through a P-element insertion screen; among them was timeless (tim), which mimicked the period phenotype. The tim mutation blocked nuclear localization of the PER protein. Young suggested that the tim protein product (TIM) might interact with PER to help it localize to the nucleus—a suggestion that would turn out to be true.

Subsequent discovery of the circadian genes clock (clk), cycle (cyc), and cryptochrome (cry) by Hall and Rosbash and double-time (dbt) by Young helped some of the last puzzle pieces click into place. By the turn of the century, they had constructed the accepted model for molecular regulation of circadian rhythms.

The simplified version is as follows: the transcription factors CLK and CYC dimerize and promote transcription of both per and tim.

click to enlarge

The PER protein heterodimerizes with TIM and accumulates in the cytoplasm. PER levels reach their peak in the middle of the night. PER-TIM dimers are stable and translocate to the nucleus where they remove CYC-CLK from the promoters, thus halting per and tim expression.

click to enlarge

CRY acts as a photoreceptor: sunlight activates CRY, which leads TIM to be ubiquitinated, causing it to dissociate from PER and to be degraded. Solo PER is phosphorylated by DBT, marking it for degradation. This loss of PER-TIM allows CYC-CLK to resume promoting per and tim expression, starting the cycle over again. Further research has revealed similar intricate biological clocks tick in all animals, including humans.

click to enlarge

With this prize, the Nobel Assembly has again recognized the contribution of research using fruit flies; Hall, Rosbash, and Young join seven previous Drosophila biologists awarded the Nobel Prize. In fact, an impressive number of Nobel Prizes have been awarded for basic science research using model organisms—a powerful approach that the Genetics Society of America advocates for as part of its mission to advance the field of genetics.

We are proud to say that Hall received the GSA Medal in 2003. All three new laureates have been long-time GSA members: Hall until his retirement, Rosbash until 2015, and Young remains one today. These outstanding members of our community show what can be done with hard work, collaboration, creativity, determination, and a pesky little fruit fly friend.

Related GENETICS Articles

Phenotypic and genetic analysis of Clock, a new circadian rhythm mutant in Drosophila melanogaster.
M S Dushay, R J Konopka, D Orr, M L Greenacre, C P Kyriacou, M Rosbash and J C Hall
GENETICS July 1, 1990 vol. 125 no. 3 557-578

Dosage compensation of the period gene in Drosophila melanogaster.
M K Cooper, M J Hamblen-Coyle, X Liu, J E Rutila and J C Hall
GENETICS November 1, 1994 vol. 138 no. 3 721-732

Molecular and Behavioral Analysis of Four period Mutants in Drosophila melanogaster Encompassing Extreme Short, Novel Long, and Unorthodox Arrhythmic Types
Melanie J. Hamblen, Neal E. White, Philip T. J. Emery, Kim Kaiserand Jeffrey C. Hall
GENETICS May 1, 1998 vol. 149 no. 1 165-178

Isolation and Analysis of Six timeless Alleles That Cause Short- or Long-Period Circadian Rhythms in Drosophila
Adrian Rothenfluh, Marla Abodeely, Jeffrey L. Price and Michael W. Young
GENETICS October 1, 2000 vol. 156 no. 2 665-675

Specific Genetic Interference With Behavioral Rhythms in Drosophila by Expression of Inverted Repeats
Sebastian Martinek and Michael W. Young
GENETICS December 1, 2000 vol. 156 no. 4 1717-1725

Identification of Circadian-Clock-Regulated Enhancers and Genes of Drosophila melanogaster by Transposon Mobilization and Luciferase Reporting of Cyclical Gene Expression
Thomas Stempfl, Marion Vogel, Gisela Szabo, Corinna Wülbeck, Jian Liu, Jeffrey C. Hall and Ralf Stanewsky
GENETICS February 1, 2002 vol. 160 no. 2 571-593

Rhythm Defects Caused by Newly Engineered Null Mutations in Drosophila’s cryptochrome Gene
Eva Dolezelova, David Dolezel and Jeffrey C. Hall
GENETICS September 1, 2007 vol. 177 no. 1 329-345; https://doi.org/10.1534/genetics.107.076513

A Key Temporal Delay in the Circadian Cycle of Drosophila Is Mediated by a Nuclear Localization Signal in the Timeless Protein
Lino Saez, Mary Derasmo, Pablo Meyer, J. Stieglitz, Michael W. Young and T. Schupbach
GENETICS July 1, 2011 vol. 188 no. 3 591-600; https://doi.org/10.1534/genetics.111.127225

NAT1/DAP5/p97 and Atypical Translational Control in the Drosophila Circadian Oscillator
Sean Bradley, Siddhartha Narayanan and Michael Rosbash
GENETICS November 1, 2012 vol. 192 no. 3 943-957; https://doi.org/10.1534/genetics.112.143248

, , ,

Scientific Editor and Programs Manager. Genetics and Molecular Biology PhD. Follow me: @_sbay | LinkedIn

View all posts by Sarah Bay »

Read more in

  • Thank you, GSA community!

    Thank you for being a member of the Genetics Society of America! As GSA’s current president, I am writing to tell you about Society projects and initiatives that we hope you will find useful in advancing your science and your career. Scientific research is a collaborative and exciting endeavor. Scientific societies like GSA exist to…

  • Collage of 2021 Rosalind Franklin Award recipients

    Where are they now? Rosalind Franklin Young Investigator Award recipients share updates on their research

    Rosalind Franklin Young Investigator Award applications are open–make sure you submit your application or nomination of a colleague by September 30, 2024.

  • University of Minnesota researchers map genome of the last living wild horse species

    The study, published in G3: Genes|Genomes|Genetics, is part of larger conservation efforts to save Przewalski’s horse.

  • Congratulations to the Spring 2024 DeLill Nasser Awardees!

    GSA is pleased to announce the recipients of the DeLill Nasser Award for Professional Development in Genetics for Spring 2024! Given twice a year to graduate students and postdoctoral researchers, DeLill Nasser Awards support attendance at meetings and laboratory courses. The award is named in honor of DeLill Nasser, a long-time GSA supporter and National Science Foundation…

  • Carolyn Damilola headshot

    Carolyn Damilola: an NFS Rising Scientist on a lifelong quest to learn more

    Carolyn Damilola is an NFS Rising Scientist from Nigeria doing respiratory system research and paving the way for scientists from underrepresented communities through mentorship.

  • Text over a blue background image: Apply for up to $2,000 for your project from the Starter Culture Microgrant Program.

    What does a good microgrant proposal look like?

    Members of the Microgrant Review Committee share their tips for a successful proposal.

  • A blurred image of a human face is shown against a dark background.

    The first piece of the facial recognition puzzle

    New research in GENETICS gives a first peek at the molecular pathway involved in recognizing faces.

  • New Senior Editor Amy MacQueen joins GENETICS

    A new senior editor is joining GENETICS in the Genome Integrity and Transmission section. We’re excited to welcome Amy MacQueen to the editorial team.

  • Close up of an adult zebrafish with blue and white stripes in an aquarium with red lighting.

    Block party on the zebrafish sex chromosome

    Research in G3 identifies a gene regulatory block of the zebrafish genome responsible for overseeing the maternal-to-zygotic-transition.

  • Lemna Minor, the common duckweed

    Unraveling the mysteries of duckweed: epigenetic insights from Spirodela polyrhiza

    Research published in G3 offers insight into the impact of DNA methylation on clonal propagation in asexually reproducing plants.

  • Luciano Marraffini headshot

    A microbiologist’s quest to understand CRISPR in bacterial self-defense

    2024 Genetics Society of America Medal recipient Luciano Marraffini determined how CRISPR-Cas systems destroy genetic targets with precision, paving the way for gene editing technology development.

  • Elaine Ostrander headshot

    Unlocking mysteries of trait and disease heritability in dogs

    2024 Edward Novitski Prize recipient Elaine Ostrander, a pioneer of the domestic dog model, discovered numerous genes affecting dog size, morphology, behavior, and disease susceptibility—many of which have relevance in humans.

  • NSF-funded BIO-LEAPS Grant to Support Culture Change in Genetics

    GSA and collaborators Personal Genetics Education & Dialogue and Reclaiming STEM Institute launch NSF-funded BIO-LEAPS project to support culture change in genetics 

    We are thrilled to announce that the Genetics Society of America (GSA) is collaborating with the Personal Genetics Education & Dialogue (PGED) based in the Department of Genetics at Harvard Medical School, and the Reclaiming STEM Institute (RSI) on a Leading Culture Change Through Professional Societies of Biology (BIO-LEAPS) grant from the U.S. National Science…

  • Daman Saluja: Navigating Science and Policy in India

    In the Paths to Science Policy series, we talk to individuals who have a passion for science policy and are active in advocacy through their various roles and careers. The series aims to inform and guide early career scientists interested in science policy. This series is brought to you by the GSA Early Care­er Scientist…

  • Deborah Andrew headshot

    A fly geneticist’s journey into discovering rules of organ development

    2024 George W. Beadle Award recipient Deborah Andrew discovered new genes and pathways in Drosophila salivary gland organogenesis. Now, her work can help optimize cell secretion in therapeutic applications and fight malaria.

  • Małgorzata Gazda's headshot

    Małgorzata Gazda: How receiving the DeLill Nasser Award helped her land her dream job

    Have you ever experienced an event that changes the course of your life, or in this case, your career? Małgorzata (Gosia) Gazda is Assistant Professor at the University of Montreal and in 2022, she received the DeLill Nasser Award for Professional Development in Genetics, which she used to attend and present at the 2022 Population,…

  • Hongyu Zhao joins GENETICS as new Senior Editor

    A new senior editor is joining GENETICS in the Statistical Genetics and Genomics section. We’re excited to welcome Hongyu Zhao to the editorial team.

  • Julio Molina Pineda at TAGC 2024

    GSA Member Julio Molina Pineda Receives DeLill Nasser Award, Shines at TAGC 2024 

    “At any career stage, the GSA membership is an amazing investment for any genetics professional!” Julio Molina Pineda is a PhD Candidate in Cell and Molecular Biology and a Research Assistant at the University of Arkansas, and a Doctoral Academy Fellow at the Lewis Lab. In 2023, Julio was awarded the DeLill Nasser Award for…

  • Ed Grell at his dissecting microscope using ether to anesthetize his flies.

    In Memoriam: Ellsworth Herman Grell (1932–2023), a pioneer of Drosophila genome engineering and annotation

    Ellsworth (Ed) Grell blessed the Drosophila community through three enduring legacies: as a pioneer of chromosome mechanics, as a primary organizer and synthesizer of genetic knowledge in Drosophila, and as a graceful mentor to those fortunate to have known him personally. Ed grew up in rural Nebraska, completed his undergraduate studies at Iowa State, and…

  • Congratulations to the #Fungal24 Poster Award winners!

    We are pleased to announce the recipients of the GSA Poster Awards for posters presented at the 32nd Fungal Genetics Conference! Undergraduate and graduate student members of GSA were eligible for the awards, and a hard-working team of judges made the determinations. Congratulations to all! Felicia Ebot Ojong, The University of Georgia My research is focused…

  • Poster presentation tips for TAGC 2024

    You’ve been selected to present a poster at The Allied Genetics Conference 2024 in March—you’ve celebrated, made plans to attend, now what? This is an exciting opportunity to showcase your research and engage with fellow members of the genetics community, so you want to make sure you’re prepared. We wanted to offer you some tips…

  • Maximize your TAGC 2024 experience 

    A guide to all that National Harbor & DC have to offer Are you joining us for The Allied Genetics Conference 2024 in March? Make the most of your #TAGC24 experience in National Harbor! We know the science will keep you busy, but you deserve to unwind and have some fun, so we’ve curated a…

  • Early Career Leadership Spotlight: Sarah Petrosky

    We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Sarah PetroskyMultimedia SubcommitteeUniversity of Pittsburgh Research Interest I am interested in understanding adaptation that has been happening recently in populations by dissecting the ways that genes underlying an adaptation…

  • TAGC 2024 Early Career Award Winners

    GSA is pleased to announce the winners of the early career awards presented at The Allied Genetics Conference 2024. These awards are specific to particular TAGC communities and recognize early career scientists’ outstanding work on their respective research organisms. The awardees will present their talks in keynote sessions at TAGC 2024.  Don’t miss the opportunity…

  • Preeminent geneticists recognized with revamped GSA Awards

    In 2022, GSA’s Board of Directors launched an audit to review the five major awards conferred by the Society. Today, we are thrilled to announce the recipients of the reimagined GSA Awards, including the new Genetics Society of America Early Career Medal. The scientists honored this year are recognized by their peers for their outstanding…

  • Fly Board funds outreach programs to spread the word about Drosophila research

    In 2020, the Fly Board voted to use part of its reserve fund to support efforts to increase trainee participation as well as equity and diversity in the Drosophila community. An awards committee decides how the money will be spent each year, and from 2020–2022, the committee posted a very broad call for applications from…

  • New members of the GSA Board of Directors: 2024–2026

    We are pleased to announce the election of four new leaders to the GSA Board of Directors: 2024 Vice President/2025 President Brenda Andrews Professor, University of Toronto It’s an honor to continue my association with the Society by serving as Vice President of the Board of Directors. I have broad knowledge of the ongoing activities…

  • New members of the GSA Board of Directors: 2025–2027

    We are pleased to announce the election of six new leaders to the GSA Board of Directors: 2025 Vice President/2026 President Cassandra Extavour Timken Professor of Organismic & Evolutionary Biology and of Molecular & Cellular Biology, Harvard University, and Howard Hughes Medical Institute Investigator “Read this,” he said, “it will change your life.” My undergraduate…

  • Congratulations, Spring 2025 Victoria Finnerty Travel Award recipients!

    The Victoria Finnerty Undergraduate Travel Award supports conference-attendance costs for undergraduate GSA members who are presenting research at the Annual Drosophila Research Conference. #Dros25 will be held in San Diego, CA from March 19–23, 2025. Victoria Finnerty, who died in February 2011, was a long-time member of the Genetics Society of America and served the Drosophila community and the genetics community at large in…

  • Meet embGAN, a revolution for cell lineage studies

    New research in GENETICS reports an automated pipeline for cell lineage tracing that massively reduces manual analysis time.