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 biological clocks and 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.[3]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. 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.[7]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 the entire biology department was devoted to genetics.[3]
Early academic career[edit]
Hall began working in Lawrence 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 Roman encouraged 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.[7]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.
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.[7]
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.[8]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 cyclesgenerated byRon
Konopkain the late 1960smight 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.[9]
Neurogenetics[edit]
In his research, Hall mainly focused onfruitless, 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.[10]
Circadian rhythm ofperiodgene and protein[edit]
Hall worked primarily withDrosophilato study the mechanism of circadian rhythms.
Rather than using the more traditional method of measuringeclosion, Hall measured
locomotor activity ofDrosophilato observe circadian rhythms.[11]
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.[12]
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.[11][13]
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.[14]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.[14]