Jeffrey Connor Hall (born May 3, 1945) is an American

geneticist A geneticist is a biologist or physician who studies genetics, the science of genes, heredity, and variation of organisms. A geneticist can be employed as a scientist or a lecturer. Geneticists may perform general research on genetic processes ...

and chronobiologist. Hall is

Professor Emeritus ''Emeritus'' (; female: ''emerita'') is an adjective used to designate a retired chair, professor, pastor, bishop, pope, director, president, prime minister, rabbi, emperor, or other person who has been "permitted to retain as an honorary title ...

of Biology at

Brandeis University , mottoeng = "Truth even unto its innermost parts" , established = , type = Private research university , accreditation = NECHE , president = Ronald D. Liebowitz , ...

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 ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...

'', Hall uncovered essential mechanisms of the circadian 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 Chronobiology is a field of biology that examines timing processes, including periodic (cyclic) phenomena in living organisms, such as their adaptation to solar- and lunar-related rhythms. These cycles are known as biological rhythms. Chronob ...

, and nominated for the T. Washington Fellows In 2017, along with Michael W. Young and

Michael Rosbash Michael Morris Rosbash (born March 7, 1944) is an American geneticist and chronobiologist. Rosbash is a professor and researcher at Brandeis University and investigator at the Howard Hughes Medical Institute. Rosbash's research group cloned the ...

, he was awarded the 2017

Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...

"for their discoveries of molecular mechanisms controlling the circadian rhythm".

Life

Early life and education

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, greatly influenced him especially by encouraging Hall to stay updated on recent events in the daily newspaper. Hall attended

Walter Johnson High School Walter Johnson High School (also known as Walter Johnson or WJ) is a public upper secondary school located in the census-designated place of North Bethesda, Maryland ( Bethesda postal address).Amherst College in 1963. However, during his time as an undergraduate student, Hall found his passion in biology. 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. 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.

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 Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately r ...

. Hershel Roman encouraged Hall to pursue postdoctoral work with Seymour Benzer, a pioneer in forward genetics, at the California Institute of Technology. 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. 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 Neuroanatomy is the study of the structure and organization of the nervous system. In contrast to animals with radial symmetry, whose nervous system consists of a distributed network of cells, animals with bilateral symmetry have segregated, defi ...

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. He is known for his eccentric lecturing style.

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. 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.

''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.

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. 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. Suspecting the ''

period Period may refer to: Common uses * Era, a length or span of time * Full stop (or period), a punctuation mark Arts, entertainment, and media * Period (music), a concept in musical composition * Periodic sentence (or rhetorical period), a concept ...

'' 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. They found that ''period'' mutations affected the courtship song in the same way they changed the circadian rhythms. ''per''^s

allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...

produced a shorter (approximately 40 second) oscillation, ''per''^l allele produced a longer (approximately 76 second) oscillation, and ''per''^o produced a song that had no regular oscillation.

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 Fru^M proteins.

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 A pupa ( la, pupa, "doll"; plural: ''pupae'') is the life stage of some insects undergoing transformation between immature and mature stages. Insects that go through a pupal stage are holometabolous: they go through four distinct stages in their ...

, Hall measured locomotor activity of ''Drosophila'' to observe circadian rhythms.

Discovery of PER protein self regulation

In 1990, while in collaboration with

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.

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 ''Pigment dispersing factor'' (''pdf'') is a gene that encodes the protein PDF, which is part of a large family of neuropeptides. Its hormonal product, pigment dispersing hormone (PDH), was named for the diurnal pigment movement effect it has i ...

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 (sLN_vs) in the Drosophila brain. From this data, Hall concluded the sLN_vs 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.

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 Cryptochromes (from the Greek κρυπτός χρώμα, "hidden colour") are a class of flavoproteins found in plants and animals that are sensitive to blue light. They are involved in the circadian rhythms and the sensing of magnetic fields ...

(CRY) plays in entrainment. Hall found that CRY is a key photoreceptor for both entrainment and regulation of locomotor activity. 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 A clock or a timepiece is a device used to measure and indicate time. The clock is one of the oldest human inventions, meeting the need to measure intervals of time shorter than the natural units such as the day, the lunar month and t ...

and Cycle (CYC) proteins form a heterodimer via the

PAS domain A Per-Arnt-Sim (PAS) domain is a protein domain found in all kingdoms of life. Generally, the PAS domain acts as a molecular sensor, whereby small molecules and other proteins associate via binding of the PAS domain. Due to this sensing capabilit ...

. 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.

References

External links

Interview with Jeffrey C. Hall and Michael Rosbash
* * * including the Nobel Lecture 7 December 2017 ''The Little Flies: Multifaceted Basic Research Coming Out Better than Intended'' {{DEFAULTSORT:Hall, Jeffrey 1945 births American geneticists American Nobel laureates Brandeis University faculty Chronobiologists Fellows of the American Academy of Arts and Sciences Living people Massry Prize recipients Members of the United States National Academy of Sciences Nobel laureates in Physiology or Medicine University of Washington alumni 21st-century American scientists 20th-century American biologists 21st-century biologists People from Brooklyn Scientists from New York City Amherst College alumni