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Jeffrey C. Hall

jeffrey c. hall, jeffrey c. hall nobel
Jeffrey Connor Hall born May 3, 1945 is an American geneticist and chronobiologist Hall is Professor Emeritus of Biology at Brandeis 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 of Drosophila melanogaster, Hall uncovered essential mechanisms of biological clocks and shed light on the foundations for sexual differentiation in the nervous system He was elected to the National Academy of Sciences for his revolutionary work in the field of chronobiology[3] Along with Michael W Young and Michael Rosbash, he was awarded the 2017 Nobel Prize in Physiology or Medicine "for their discoveries of molecular mechanisms controlling the circadian rhythm"[4][5]

Contents

  • 1 Life
    • 11 Early life and education
    • 12 Early academic career
    • 13 Academic adversities
  • 2 Drosophila courtship behavior
    • 21 Discovery of period connection
    • 22 Neurogenetics
  • 3 Circadian rhythm of period gene and protein
    • 31 Discovery of PER protein self regulation
    • 32 Discovery of synchronization between cells
    • 33 Refining the transcription-translation negative feedback loop model
  • 4 References
  • 5 External links

Life

Early life and education

Jeffrey Hall was born in Brooklyn, New York and raised in the suburbs of Washington DC, while his father worked as a reporter for the Associated Press, covering the US 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 attended Walter Johnson High School in 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 at Amherst College in 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 of Drosophila while working in Ives' lab, a passion that has permeated his research Under the supervision of Ives, Hall studied recombination and translocation induction in Drosophila 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

Hall began working in Lawrence Sandler's laboratory during graduate school in 1967 Hall worked with Sandler on analyzing age-dependent enzyme changes in Drosophila, with a concentration on the genetic control of chromosome behavior in meiosis Hershel Roman encouraged Hall to pursue postdoctoral work with Seymour 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 about Drosophila neuroanatomy and 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

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 was Michael 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]

Drosophila courtship behavior

Hall's work with Drosophila courtship 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 of Drosophila courtship and led him to the subsequent career path of investigation into Drosophila courtship[3]

Discovery of period connection

In the late 1970s, through a collaborative work with Florian von Schilcher, Hall successfully identified the nervous system regions in Drosophila that 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 that Drosophila courtship song was produced rhythmically with a normal period of about one minute[3]

Suspecting the period mutation for abnormal sleep-wake cycles—generated by Ron Konopka in 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 that period mutations affected the courtship song in the same way they changed the circadian rhythms pers allele produced a shorter approximately 40 second oscillation, perl allele produced a longer approximately 76 second oscillation, and pero produced a song that had no regular oscillation[10]

Neurogenetics

In his research, Hall mainly focused on flies with the fruitless gene, which he began studying during his postdoctoral years The fruitless 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 cloned fruitless Through subsequent research with the cloned fruitless, Hall confirmed the previously suspected role of fruitless as the master regulator gene for courtship By examining several fru mutations, 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 FruM proteins[11]

Circadian rhythm of period gene and protein

Hall worked primarily with Drosophila to study the mechanism of circadian rhythms Rather than using the more traditional method of measuring eclosion, Hall measured locomotor activity of Drosophila to observe circadian rhythms[12]

Discovery of PER protein self regulation

In 1990, while in collaboration with Michael Rosbash and 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 in Drosophila In this original model, per expression led to an increase of PER After a certain concentration of PER, the expression of per decreased, causing PER levels to decrease, once again allowing per to be expressed[13]

Discovery of synchronization between cells

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 the pigment dispersing factor protein 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

In 1998, Hall contributed to two discoveries in Drosophila that refined the TTFL model The first discovery involved the role Cryptochrome 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 Drosophila per and timeless tim circadian genes were regulated Hall discovered that CLOCK and Cycle CYC proteins form a heterodimer via the PAS domain Upon dimerizing, the two proteins bind to the E box promoter element of the two genes via the bHLH domain to induce expression of per and tim mRNA[15]

References

  1. ^ "American Men and Women of Science: The physical and biological sciences" Bowker October 2, 1989 Retrieved October 2, 2017 – via Google Books 
  2. ^ Jeff Hall – Brandeis Faculty Guide
  3. ^ a b c d e f g h i Nuzzo, Regina November 15, 2005 "Profile of Jeffrey C Hall" PDF PNAS 102: 16547–16549 doi:101073/pnas0508533102 PMC 1283854  PMID 16275901 
  4. ^ Cha, Arlene Eujung October 2, 2017 "Nobel in physiology, medicine awarded to three Americans for discovery of 'clock genes'" Washington Post Retrieved October 2, 2017 
  5. ^ "The 2017 Nobel Prize in Physiology or Medicine – Press Release" The Nobel Foundation October 2, 2017 Retrieved October 2, 2017 
  6. ^ Hall, Jeffrey C September 16, 2009 "The Stand of the US Army at Gettysburg" Indiana University Press Retrieved October 2, 2017 – via Google Books 
  7. ^ Rees, Ian November 1, 2017 "WJ Alum wins Nobel Prize in Medicine" The Pitch Retrieved March 2, 2018 
  8. ^ a b c Hall, Jeffrey December 12, 2008 "Jeffrey CHall" PDF Current Biology 
  9. ^ Clyne, Dylan April 2008 "Sex-Specific Control and Tuning of the Pattern Generator for Courtship Song in Drosophila" Cell 133: 354–63 doi:101016/jcell200801050 PMID 18423205 
  10. ^ Greenspan, R J; Ferveur, J F 2000 "Courtship in Drosophila" Annual Review of Genetics 34: 205–232 doi:101146/annurevgenet341205 ISSN 0066-4197 PMID 11092827 
  11. ^ Rideout, Elizabeth J; Dornan, Anthony J; Neville, Megan C; Eadie, Suzanne; Goodwin, Stephen F Apr 2010 "Control of sexual differentiation and behavior by the doublesex gene in Drosophila melanogaster" Nature Neuroscience 13 4: 458–466 doi:101038/nn2515 ISSN 1546-1726 PMC 3092424  PMID 20305646 
  12. ^ a b Dunlap, JC January 1999 "Molecular Bases for Circadian Clocks" Cell 96: 271–290 doi:101016/S0092-86740080566-8 PMID 9988221 Retrieved April 9, 2015 
  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 doi:101126/science28053691564 ISSN 0036-8075 PMID 9616112 Retrieved April 9, 2015 
  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:101038/nrg1633 ISSN 1471-0056 PMC 2735866  PMID 15951747 Retrieved April 9, 2015 
  15. ^ a b Kume, 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: 193–205 doi:101016/S0092-86740081014-4 PMID 10428031 Retrieved April 9, 2015 CS1 maint: Explicit use of et al link

External links

  • Interview with Jeffrey C Hall and Michael Rosbash
  • Hardin, Paul E; Hall, Jeffrey C; Rosbash, Michael February 8, 1990 "Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels" Nature 343 6258: 536–540 doi:101038/343536a0 PMID 2105471 Retrieved April 23, 2015 
  • Renn, SC; Park, JH; Rosbash, M; Hall, JC; Taghert, PH December 1999 "A pdf Neuropeptide Gene Mutation and Ablation of PDF Neurons Each Cause Severe Abnormalities of Behavioral Circadian Rhythms in Drosophila" Cell 99: 791–802 doi:101016/S0092-86740081676-1 PMID 10619432 Retrieved April 23, 2015 

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