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Jeffrey C. Hall

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Jeffrey C. Hall
Jeffrey C. Hall at Nobel Prize press conference in Stockholm, December 2017
Born
Jeffrey Connor Hall[1]

(1945-05-03)May 3, 1945(age 79)
New York City,U.S.
EducationAmherst College(BA)
University of Washington, Seattle(MS,PhD)
Known forCloning theperiod gene
AwardsGenetics Society of America Medal(2003)
Gruber Prize in Neuroscience(2009)
Louisa Gross Horwitz Prize(2011)
Gairdner Foundation International Award(2012)
Shaw Prize(2013)
Wiley Prize(2013)
Nobel Prize in Physiology or Medicine(2017)
Scientific career
FieldsGenetics
InstitutionsBrandeis University
University of Maine
ThesisGenetic analysis of two alleles of a recombination-deficient mutant in drosophila melanogaster(1971)
Doctoral advisorLawrence Sandler
Other academic advisorsSeymour Benzer,Herschel L. Roman

Jeffrey Connor Hall(born May 3, 1945) is an Americangeneticistandchronobiologist.Hall isProfessor Emeritusof Biology atBrandeis University[2]and currently resides in Cambridge, Maine.

Hall spent his career examining the neurological component of fly courtship and behavioral rhythms. Through his research on the neurology and behavior ofDrosophila melanogaster,Hall uncovered essential mechanisms of thecircadian clocksand shed light on the foundations for sexual differentiation in the nervous system. He was elected to theNational Academy of Sciencesfor his revolutionary work in the field ofchronobiology,and nominated for the T. Washington Fellows[3]

In 2017, along withMichael W. YoungandMichael Rosbash,he was awarded the 2017Nobel Prize in Physiology or Medicine"for their discoveries of molecular mechanisms controlling the circadian rhythm".[4][5]

Life[edit]

Early life and education[edit]

Jeffrey Hall was born in Brooklyn, New York and raised in the suburbs of Washington D.C., while his father worked as a reporter for the Associated Press, covering the U.S. Senate. Hall's father, Joseph W. Hall,[6]greatly influenced him especially by encouraging Hall to stay updated on recent events in the daily newspaper. Hall attendedWalter Johnson High Schoolin Bethesda, Maryland, graduating in 1963.[7]As a good high school student, Hall planned to pursue a career in medicine. Hall began pursuing a bachelor's degree atAmherst Collegein 1963. However, during his time as an undergraduate student, Hall found his passion in biology.[3]For his senior project, to gain experience in formal research, Hall began working with Philip Ives. Hall reported that Ives was one of the most influential people he encountered during his formative years.[8]Hall became fascinated with the study ofDrosophilawhile working in Ives' lab, a passion that has permeated his research. Under the supervision of Ives, Hall studied recombination andtranslocationinduction inDrosophila.The success of Hall's research pursuits prompted department faculty to recommend that Hall pursue graduate school at University of Washington in Seattle, where an entire department was devoted to genetics.[3]

Early academic career[edit]

Hall began working inLawrence Sandler's laboratory during graduate school in 1967. Hall worked with Sandler on analyzing age-dependent enzyme changes inDrosophila,with a concentration on the genetic control of chromosome behavior inmeiosis.Hershel Romanencouraged Hall to pursue postdoctoral work withSeymour Benzer,a pioneer in forward genetics, at the California Institute of Technology.[3]In an interview, Hall regarded Roman as an influential figure in his early career for Roman fostered camaraderie in the laboratory and guided nascent professionals.[8]Upon completing his doctoral work, Hall joined Benzer's laboratory in 1971. In Benzer's lab, Hall worked with Doug Kankel who taught Hall aboutDrosophilaneuroanatomyand neurochemistry. Although Hall and Kankel made great progress on two projects, Hall left Benzer's laboratory before publishing results. In Hall's third year as a postdoctoral researcher, Roman contacted Hall regarding faculty positions that Roman had advocated for Hall. Hall joined Brandeis University as an Assistant Professor of Biology in 1974.[3]He is known for his eccentric lecturing style.[according to whom?]

Academic adversities[edit]

During his time working in the field of chronobiology, Hall faced many challenges when attempting to establish his findings. Specifically, his genetic approach to biological clocks (see period gene section) was not easily accepted by more traditional chronobiologists. When conducting his research on this particular topic, Hall faced skepticism when trying to establish the importance of a sequence of amino acids he isolated. While working on this project the only other researcher working on a similar project wasMichael Young.[3]

Hall not only faced hurdles when attempting to establish his own work, but also found the politics of research funding frustrating. In fact these challenges are one of the primary reasons why he left the field. He felt that the hierarchy and entry expectations of biology are preventing researchers from pursuing the research they desire. Hall believed the focus should be on the individual's research; funding should not be a limiting factor on the scientist, but instead give them the flexibility to pursue new interests and hypotheses. Hall expressed that he loves his research and flies, yet feels that the bureaucracy involved in the process prevented him from excelling and making new strides in the field.[8]

Drosophilacourtship behavior[edit]

Hall's work withDrosophilacourtship behavior began as a collaborative work with Kankel to correlate courtship behaviors with genetic sex in various regions of the nervous systems using fruit fly sex mosaics during the last months of his postdoctoral years in Benzer's laboratory. This work triggered his interest in the neurogenetics ofDrosophilacourtship and led him to the subsequent career path of investigation intoDrosophilacourtship.[3]

Discovery ofperiodconnection[edit]

In the late 1970s, through a collaborative work with Florian von Schilcher, Hall successfully identified the nervous system regions inDrosophilathat contributed to the regulation of male's courtship songs.[9]Hall realized from this study that courtship singing behavior was one of the elegantly quantifiable features of courtship and decided to study this topic further. In the subsequent research with a postdoctoral fellow in his lab, Bambos Kyriacou, Hall discovered thatDrosophilacourtship song was produced rhythmically with a normal period of about one minute.[3]

Suspecting theperiodmutation for abnormal sleep-wake cycles—generated byRon Konopkain the late 1960s—might also alter courtship song cycles, Hall and Kyriacou tested the effect of mutations in the period on courtship song.[3]They found thatperiodmutations affected the courtship song in the same way they changed the circadian rhythms.persalleleproduced a shorter (approximately 40 second) oscillation,perlallele produced a longer (approximately 76 second) oscillation, andperoproduced a song that had no regular oscillation.[10]

Neurogenetics[edit]

In his research, Hall mainly focused on flies with thefruitless gene,which he began studying during his postdoctoral years. Thefruitless (fru)mutant was behaviorally sterile. Furthermore, they indiscriminately courted both females and males, but did not try to mate with either. This behavior was identified in the 1960s, but it had been neglected until Hall's group began to investigate the topic further. In the mid-1990s, through a collaborative work with Bruce Baker at Stanford University and Barbara Taylor at Stanford University, Hall successfully clonedfruitless.Through subsequent research with the clonedfruitless,Hall confirmed the previously suspected role offruitlessas the master regulator gene for courtship. By examining severalfrumutations, Hall discovered that males performed little to no courtship toward females, failed to produce the pulse song component of courtship song, never attempted copulation, and exhibited increased inter-male courtship in the absence of FruMproteins.[11]

Circadian rhythm ofperiodgene and protein[edit]

Hall worked primarily withDrosophilato study the mechanism ofcircadian rhythms.Rather than using the more traditional method of measuringeclosion,Hall measured locomotor activity ofDrosophilato observe circadian rhythms.[12]

Discovery of PER protein self regulation[edit]

In 1990, while in collaboration withMichael Rosbashand Paul Hardin, Hall discovered that the Period protein (PER) played a role in suppressing its own transcription. While the exact role of PER was unknown, Hall, Rosbash, and Hardin were able to develop a negative transcription-translation feedback loop model (TTFL) that serves as a central mechanism of the circadian clock inDrosophila.In this original model,perexpression led to an increase of PER. After a certain concentration of PER, the expression ofperdecreased, causing PER levels to decrease, once again allowingperto be expressed.[13]

Discovery of synchronization between cells[edit]

In 1997, Hall was a part of group with Susan Renn, Jae Park, Michael Rosbash, and Paul Taghert that discovered genes that are a part of the TTFL are expressed in cells throughout the body. Despite these genes being identified as necessary genes to the circadian clock, there was a variety of levels of expressions in various parts of the body; this variation was observed on the cellular level. Hall succeeded in entraining separate tissues to different light-dark cycles at the same time. Hall didn't discover the element that synchronizes cells until 2003. He found that thepigment dispersing factorprotein (PDF) helps control the circadian rhythms, and in turn locomotor activity, of these genes in cells. This was localized to small ventral lateral neurons (sLNvs) in the Drosophila brain. From this data, Hall concluded the sLNvs serve as the primary oscillator in Drosophila and PDF allows for synchrony between cells. He was awarded the 2017 Nobel Prize in Medicine or Physiology.[12][14]

Refining the transcription-translation negative feedback loop model[edit]

In 1998, Hall contributed to two discoveries inDrosophilathat refined the TTFL model. The first discovery involved the roleCryptochrome(CRY) plays in entrainment. Hall found that CRY is a key photoreceptor for both entrainment and regulation of locomotor activity.[15]He hypothesized CRY may not be just an input to the circadian system, but also a role as a pacemaker itself. In the same year, Hall discovered how the Drosophilaperandtimeless(tim) circadian genes were regulated. Hall discovered thatCLOCKandCycle(CYC) proteins form a heterodimer via thePAS domain.Upon dimerizing, the two proteins bind to theE boxpromoter element of the two genes via thebHLHdomain to induce expression ofperandtimmRNA.[15]

References[edit]

  1. ^American Men and Women of Science: The physical and biological sciences.Bowker. October 2, 1989.ISBN978-0-8352-1127-7.RetrievedOctober 2,2017– via Google Books.
  2. ^Jeff Hall– Brandeis Faculty Guide
  3. ^abcdefghiNuzzo, Regina(November 15, 2005)."Profile of Jeffrey C. Hall".PNAS.102(46): 16547–16549.Bibcode:2005PNAS..10216547N.doi:10.1073/pnas.0508533102.PMC1283854.PMID16275901.
  4. ^Cha, Arlene Eujung (October 2, 2017)."Nobel in physiology, medicine awarded to three Americans for discovery of 'clock genes'".The Washington Post.RetrievedOctober 2,2017.
  5. ^"The 2017 Nobel Prize in Physiology or Medicine – Press Release".The Nobel Foundation. October 2, 2017.RetrievedOctober 2,2017.
  6. ^Hall, Jeffrey C. (September 16, 2009).The Stand of the U.S. Army at Gettysburg.Indiana University Press.ISBN978-0-253-00329-4.RetrievedOctober 2,2017– via Google Books.
  7. ^Rees, Ian (November 1, 2017)."WJ Alum wins Nobel Prize in Medicine".The Pitch.RetrievedMarch 2,2018.
  8. ^abcHall, Jeffrey (December 12, 2008)."Jeffrey C.Hall"(PDF).Current Biology.
  9. ^Clyne, Dylan (April 2008)."Sex-Specific Control and Tuning of the Pattern Generator for Courtship Song in Drosophila".Cell.133(2): 354–63.doi:10.1016/j.cell.2008.01.050.PMID18423205.S2CID17127836.
  10. ^Greenspan, R. J.; Ferveur, J. F. (2000). "Courtship in Drosophila".Annual Review of Genetics.34:205–232.doi:10.1146/annurev.genet.34.1.205.ISSN0066-4197.PMID11092827.
  11. ^Rideout, Elizabeth J.; Dornan, Anthony J.; Neville, Megan C.; Eadie, Suzanne; Goodwin, Stephen F. (April 2010)."Control of sexual differentiation and behavior by the doublesex gene in Drosophila melanogaster".Nature Neuroscience.13(4): 458–466.doi:10.1038/nn.2515.ISSN1546-1726.PMC3092424.PMID20305646.
  12. ^abDunlap, JC (January 1999)."Molecular Bases for Circadian Clocks".Cell.96(2): 271–290.doi:10.1016/S0092-8674(00)80566-8.PMID9988221.S2CID14991100.
  13. ^Gekakis, Nicholas; Staknis, David; Nguyen, Hubert B.; Davis, Fred C.; Wilsbacher, Lisa D.; King, David P.; Takahashi, Joseph S.; Weitz, Charles J. (June 5, 1998). "Role of the CLOCK Protein in the Mammalian Circadian Mechanism".Science.280(5369): 1564–1569.Bibcode:1998Sci...280.1564G.doi:10.1126/science.280.5369.1564.ISSN0036-8075.PMID9616112.
  14. ^Bell-Pedersen, Deborah;Cassone, Vincent M.; Earnest, David J.; Golden, Susan S.; Hardin, Paul E.; Thomas, Terry L.; Zoran, Mark J. (July 2005)."Circadian rhythms from multiple oscillators: lessons from diverse organisms".Nature Reviews Genetics.6(7): 544–556.doi:10.1038/nrg1633.ISSN1471-0056.PMC2735866.PMID15951747.
  15. ^abKume, K; Zylka, MJ; Sriram, S; et al. (July 1999)."mCRY1 and mCRY2 Are Essential Components of the Negative Limb of the Circadian Clock Feedback Loop".Cell.98(2): 193–205.doi:10.1016/S0092-8674(00)81014-4.PMID10428031.S2CID15846072.

External links[edit]

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