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Jeffrey C. Hall, Michael Rosbash, and Michael W. Young first met in the early 1980s when they were all working at Brandeis University in Massachusetts, USA. At the time, Hall and Rosbash were studying the circadian rhythm in fruit flies, while Young was studying the circadian rhythm in hamsters. Their research interests intersected when they discovered that fruit flies had a similar genetic mechanism for regulating the circadian rhythm as hamsters. Hall, Rosbash, and Young began collaborating on research, sharing their expertise in genetics and molecular biology to uncover the molecular mechanisms underlying the biological clock. Their collaboration proved to be highly productive, and together they made several groundbreaking discoveries related to the circadian rhythm, including the identification of the "period" and "timeless" genes and the characterization of the proteins they encode. This work ultimately led to their joint receipt of the 2017 Nobel Prize in Physiology or Medicine for their contributions to understanding the molecular mechanisms that control the circadian rhythm.

Source:

https://www.nobelprize.org/prizes/medicine/2017/press-release/

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The history of the circadian rhythm can be traced back to ancient times. Many organisms, including humans, have evolved to adapt their biological processes to the Earth's 24-hour day-night cycle, which is regulated by the rotation of the planet on its axis. The concept of the circadian rhythm was first studied in the early 20th century by the French scientist Jean-Jacques d'Ortous de Mairan, who observed that the leaves of the Mimosa pudica plant continued to open and close in a regular pattern even when kept in constant darkness. He hypothesized that this periodicity was due to an internal biological clock within the plant. Further research into the circadian rhythm was conducted by a number of scientists in the following decades, including Jurgen Aschoff, who coined the term "circadian" in the 1950s to describe biological rhythms that cycle over a period of approximately 24 hours.

Sources:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138759/#:~:text=The%20first%20scientific%20observation%20of%20circadian%20rhythm%20was%20made%20in,1%5D%2C%20%5B2%5D.

https://en.wikipedia.org/wiki/Circadian_rhythm

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Fruit flies are what Jeffrey C. Hall used to make his discoveries. In the 20th century, scientists began studying the genetics of fruit flies, which were found to be useful model organisms for genetic research. Fruit flies have been used extensively in genetic research because they are easy to breed, have a short generation time, and produce a large number of offspring. They also have a relatively small genome, which makes it easier to identify and study specific genes. Also, fruit flies share many genetic and biochemical similarities with humans, despite being very different organisms.

Source:

https://www.upstate.edu/cvr/investigators/francesca-pignoni-phd/why-the-fly.php#:~:text=The%20fruit%20fly%20has%20been,humans.

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In the 1980s, Jeffrey C. Hall, Michael Rosbash, and Michael W. Young began studying fruit flies to identify genes that controlled the circadian rhythm. They discovered a gene called "period" that was essential for regulating the biological clock. They used a technique called forward genetics, which involves identifying mutations that disrupt a specific biological process, and then identifying the genes that are responsible for that process. To do this, the researchers subjected thousands of fruit flies to random mutagenesis and then screened the resulting offspring for disruptions to their circadian rhythm. They identified a group of flies that exhibited an abnormal circadian rhythm, and found that these flies had a mutation in a previously unknown gene that they named "period". Further research showed that the "period" gene encoded a protein that accumulated in cells during the night and was degraded during the day, providing a feedback mechanism for regulating the biological clock. This discovery was a major breakthrough in the study of the circadian rhythm, and paved the way for further research into the molecular mechanisms that control the biological clock.

Source: https://en.wikipedia.org/wiki/Period_(gene)

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Characterization of the "Period" Protein

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Characterization of the "Period" Protein

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Once Jeffrey C. Hall, Michael Rosbash, and Michael W. Young identified the "period" gene in fruit flies, they set out to characterize the protein encoded by this gene. Through a series of experiments, they discovered that the "period" protein accumulated in cells during the night and was degraded during the day, providing a feedback mechanism for regulating the biological clock. They also found that the "period" protein interacted with other proteins in the cell to form a complex that regulated the activity of other genes involved in the circadian rhythm. In addition, they discovered that mutations in the "period" gene could lead to disruptions in the circadian rhythm and affect behavior, such as sleep and wake cycles, in fruit flies. This finding provided further evidence that the "period" gene was an important regulator of the biological clock.

Sources:

https://en.wikipedia.org/wiki/Period_(gene)

https://www.uniprot.org/uniprotkb/P07663/entry

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After discovering the "period" gene, Jeffrey C. Hall, Michael Rosbash, and Michael W. Young continued their research into the molecular mechanisms that control the circadian rhythm in fruit flies. In the mid-1990s, they made another major breakthrough when they identified a second gene that was involved in regulating the biological clock, which they named "timeless". To identify the "timeless" gene, the researchers used a technique called reverse genetics, which involves using a known gene sequence to identify mutations that disrupt its function. They screened thousands of fruit flies for mutations that affected the circadian rhythm, and identified a group of flies that had a mutation in a previously unknown gene that they named "timeless". Further research showed that the "timeless" gene encoded a protein that worked together with the "period" protein to form a complex that regulated the activity of other genes involved in the circadian rhythm. The "timeless" protein also played a role in the degradation of the "period" protein, providing an additional layer of regulation for the biological clock.

Source: https://en.wikipedia.org/wiki/Timeless_(gene)#:~:text=In%201994%2C%20timeless%20was%20discovered,via%20a%20P%20element%20screen.

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The "period" and "timeless" genes and their encoded proteins work together to form a feedback loop that helps to regulate the biological clock. This feedback loop helps to ensure that the circadian rhythm stays on a 24-hour cycle, even in the absence of external cues such as light and dark. It is a key mechanism by which genes and proteins regulate the biological clock.

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3859310/#:~:text=Circadian%20rhythms%20in%20mammals%20are,dimer%2C%20repressing%20their%20own%20expression.

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Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered that the genetic mechanisms controlling the circadian rhythm were highly conserved across many species, including fruit flies, mice, and humans. This means that the same genes and proteins that regulate the biological clock in fruit flies are also involved in regulating the circadian rhythm in humans. This conservation is important because it suggests that the basic mechanisms of the biological clock have been present in organisms for hundreds of millions of years, and have been conserved throughout evolution due to their fundamental importance for survival.

Sources:

https://academic.oup.com/icb/article/53/1/89/629957

https://pubmed.ncbi.nlm.nih.gov/28527179/

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Jeffrey C. Hall's Upbringing (Individual Entry)

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Jeffrey C. Hall's Upbringing (Individual Entry)

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Jeffrey C. Hall was born on May 3, 1945, in Brooklyn, New York City, United States. He grew up in a Jewish family in New York City, and later moved to Southern California with his family when he was a teenager. Hall received his undergraduate degree from Amherst College in 1967, and his Ph.D. in Genetics from the University of Washington in 1971. After receiving his Ph.D. in Genetics from the University of Washington in 1971, Jeffrey C. Hall went on to pursue postdoctoral research at the California Institute of Technology (Caltech) in Pasadena, California. In 1974, Hall joined the faculty at Brandeis University in Waltham, Massachusetts, where he spent most of his academic career. He was appointed as a professor of Biology in 1988 and later became the Director of the Center for Behavioral Genomics at Brandeis. He was known for his eccentric teaching style. During his time at Brandeis, Hall focused his research on the genetics of behavior and the biological mechanisms underlying circadian rhythms in fruit flies.

Source: https://en.wikipedia.org/wiki/Jeffrey_C._Hall

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The discovery of the biological clock is important to modern-day neuroscience for several reasons. Firstly, it impacts human health. Disruptions to the biological clock have been linked to various health problems, including sleep, metabolic, and mood disorders. Understanding the molecular mechanisms that control the clock could help us develop new treatments and therapies for these conditions.

Source: https://www.sciencedaily.com/releases/2011/01/110126131540.htm#:~:text=Not%20only%20does%20the%20research,of%20years%20to%20early%20life