How Jeffrey Hall's Fruit Fly Fascination Cracked the Circadian Rhythm

Jeffrey Hall's fascination with fruit flies has helped us understand how genetics and hormones control animal circadian rhythms.
Christopher McFadden

Jeffrey C. Hall is a Nobel Prize-winning geneticist whose interest in fruit flies has proved revolutionary for our understanding of our circadian rhythms. Here we explore the man behind the Nobel Prize and briefly touch on why his work was so important. 


Who is Jeffrey C. Hall?

Hall is an American geneticist who is best known for his research into the behavior and biological rhythms of the fruit fly Drosophila melanogaster. He was born on the 3rd of May, 1945 in Brooklyn, New York and was jointly awarded the Nobel Prize for Physiology or Medicine for his contributions to the discovery of how animal cells track time. 

Hall spent his youth living outside Washington D. C. where his father worked for the Associated Press covering the 'toings' and 'froings' of the U.S. Senate. His father would prove to be a great influence on Hall and instilled a need for him to keep up to date with current affairs.

He had originally planned to pursue a career in medicine but soon became enraptured by fruit flies during his undergraduate studies at Amherst College.

Jeffrey hall genetics
Source: Bengt Nyman/Wikimedia Commons

Whilst at college, Hall worked under Philip Ives, who was also a major influence on him. Under Ives' supervision, Hall studied the recombination and translocation induction in Drosophila specimens. 

Based on his great work at Amherst, he was persuaded to pursue a Ph.D. in genetics at the University of Washington, Seattle. 

After a stint at the California Institute of Technology in Pasadena, Hall began to work at Brandeis University in Waltham, Massachusetts in 1974. 

In 2004, Hall was named Professor Emeritus of Biology at Brandeis. Hall then joined the University of Maine as an adjunct professor. He later became the Libra Professor of Neurogenetics.

Jeffrey taught at the university until 2012.

In addition to his well-deserved Nobel Prize, Hall was the recipient of various other honors during his career, including, but not limited to: -

Hall has also served as an editor for several scientific journals and was an elected member of multiple scientific organizations, including the American Academy of Arts and Sciences (2001) and the National Academy of Sciences (2003).

What scientific field does Jeffrey Hall work in?

Hall's main scientific discipline is genetics. 

His life's work has mainly focussed on the molecular mechanisms that underlie the biological rhythm of fruit flies. His work, in no small part, has enabled scientists to gain insights into the circadian rhythm of animals. 

"In our cells, an internal clock helps us to adapt our biological rhythm to the different phases of day and night. Jeffrey Hall, Michael Rosbash and Michael Young studied fruit flies to figure out how this clock-works.

In 1984 they managed to identify a gene that encodes a protein that accumulates during the night but is degraded during the day. They also identified additional proteins that form part of a self-regulating biological clockwork in the fruit fly's cells.

The same principles have been shown to apply to other animals and plants." - Nobel Prize

In case you are not aware, this is the self-regulating 24-hour biological clock that drives the behavior of many animals, including human beings. For this, he was jointly awarded the Nobel Price in Physiology or Medicine in 2017. 

He shared the prize with two other American scientists,  Michael Rosbash and Michael W. Young.

How courtship in fruit flies led to his Hall's Nobel Prize

Hall's work has mainly focused on the neurogenetics of courtship and biological rhythms in fruit flies. As part of this research, Hall, while studying regions of the flies' nervous system, discovered parts that help regulate courtship "singing" behavior

He, with one of his postdoctoral students, found that the flies' "songs" occur periodically and at regular intervals. His team subsequently found that mutant flies appeared to conduct their courtship rituals at abnormal times during daily sleep-wake cycles. 

"The mutations underlying the sleep-wake disturbances were in an unknown gene that had been named the period gene owing to its apparent influence on circadian rhythm." - Encyclopedia Britannica

jeffery hall circadian rythym
Human circadian rhythm. Source: Nobel Prize 

After receiving some criticism from his peers during the mid-1980s, Hall collaborated with Roshbash, to successfully locate and isolate this gene. At around the same time, another researcher at Rockefeller University, New York, Young, independently managed the same feat.

Robash and Hall later discovered that the levels of the so-called period gene product, the Period protein (PER), seemed to fluctuate in the fruit fly brain. From their studies, they found that PER builds up at night and declines during the day. 

These fluctuations, or oscillations, in PER levels also appeared to be the product of a negative feedback loop. PER, they found, was produced by the fruit fly until it reached a certain critical level.

Once reached, the synthesis of PER would automatically turn off. 

"In this way, the protein’s production was regulated in a continuous 24-hour cycle. Hall, Rosbash, and Young later discovered additional rhythm-regulating genes and further elucidated the mechanisms by which light and other factors influence timing in the circadian clock." - Encyclopedia Britannica

Later work on this very subject in the 1990s helped Hall, Robash, and others to find that their new gene was also expressed in other cells of the flies' bodies. 

What is the relevance of Hall's fruit fly research to other animals?

Hall's work on studying the circadian rhythm of fruit flies has proved to be revolutionary for our understanding of the circadian rhythm.

Hall also managed to discover that the gene expresses itself in response to dark-light cycles - - like day and night. He found something called the pigment dispersing factor protein (PDF) helps control their circadian rhythms.

PDF, Hall also discovered, helps control the locomotor activity of these genes in cells. PDF was localized to small ventral lateral neurons (sLNvs) in the Drosophila brain.

Based on this discovery, Hall and his colleagues were able to ascertain that these neurons act like a kind of pacemaker for the circadian rhythm in fruit flies. He also concluded that that PDF was the main protein for maintaining synchrony in other cells of the body. 

jeffery hall fruit flies
Source: Sanjay Acharya/Wikimedia Commons

In human beings, this rhythm helps regulate when we sleep, eat, release hormones, and raise/lower blood pressures. A person's habits can easily disrupt this natural cycle by working late shifts, traveling long-distances by plane, and staying up late at night.

While disruption like this can have serious implications for your general health, they can, thankfully, be reset. 

This rhythm is controlled by similar genes and expressed proteins in other animals as in the fruit fly. In humans, the suprachiasmatic nucleus (SCN) located in the hypothalamus is analogous to the fruit flies' small ventral lateral neurons (sLNvs).

A protein called neuropeptide vasoactive intestinal peptide (VIP) is also a homolog for fruit fly PDF in humans.

The neural and hormonal activities of SCN and VIP respectively, regulate many different body functions in a 24-hour cycle, using around 20,000 neurons.

"Every living organism on this planet responds to the sun," said Sir Paul Nurse (who shared the 2001 Nobel prize).

"All plant and animal behavior is determined by the light-dark cycle. We on this planet are slaves to the sun. The circadian clock is embedded in our mechanisms of working, our metabolism, it’s embedded everywhere, it’s a real core feature for understanding life." he added. 

Selected facts about Jeffrey Hall

1. Hall was jointly awarded the Nobel Prize for Physiology or Medicine in 2017.

2. Hall's work has enabled scientists to uncover the genes and hormones that help control an animal's circadian rhythm.

3. Hall was born in May of 1945 and is currently 74 years old. 

4. Hall's fascination with fruit flies began during his undergraduate studies at Amherst College. It would dictate the rest of his academic and scientific career.

5. Hall has various awards in recognition for his work including The Genetics Society of America Medal, The Gruber Prize in Neuroscience, The Louisa Gross Horwitz Prize, The Gairdner Foundation International Award, The Shaw Prize and the Wiley Prize.

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