The Shaw Prize in Life Science and Medicine 2013 is awarded to Jeffrey C Hall, Professor Emeritus of Brandeis University, Michael Rosbash, Professor of Biology and Investigator of HHMI at Brandeis University, and Michael W Young, Vice President for Academic Affairs and Professor at Rockefeller University for their discovery of molecular mechanisms underlying circadian rhythms.
We are all familiar with biological rhythms, whether in our own regular sleepiness at bedtime and the distressing effects of jet lag or the behavior of flowers that open by day and close at night. Indeed, these daily (circadian, latin for ‘about a day’) rhythms have been known throughout history, but the nature of the underlying clock had remained obscure until studies on the fruit fly by the late Seymour Benzer uncovered a gene that could be mutated to make the clock run faster or slower or not at all. In itself, this did not explain anything about how the clock worked, but it opened the door for this year’s Shaw Prize laureates, Jeffrey C Hall, Michael Rosbash and Michael W Young, who conducted a series of groundbreaking studies on the mutant fruit flies, uncovering the molecular mechanisms that control circadian rhythms not only in flies, but, remarkably, also in humans.
Hall and Rosbash, working as a team at Brandeis University, and Young, working independently at Rockefeller University, made the first breakthrough in 1984 by cloning the Period gene, the gene in the fruit fly Drosophila melanogaster that was known to alter the animal's daily rhythms when mutated. The next breakthrough came with the discovery, by Hall and Rosbash, that both the mRNA and protein encoded by the Period gene show circadian oscillations in abundance in the Drosophila brain. Moreover, these rhythmic oscillations are altered in flies with Period gene mutations that alter the fly's daily rhythms. This provided the first clue to the fundamental mechanism controlling the circadian clock: a feedback loop in which the protein product of the Period gene cyclically represses its own production on a 24-hour timescale. Subsequent work by Young and the Hall/Rosbash team revealed additional genes involved in the clock mechanism and provided detailed information on how the products of those genes function to control the daily oscillating levels of Period mRNA and protein that govern the animals daily rhythms, as well as the mechanisms that allow for the clock to be reset by light.
We now know that the same fundamental mechanisms of circadian rhythms first identified by Hall, Rosbash and Young in the fruit fly also operate in other organisms, including humans. Indeed, links have already been made between these mechanisms and human disease, with two different counterparts of a fly circadian rhythm gene showing associations with hereditary syndromes that affect circadian patterns of sleep in humans.
Life Science and Medicine Selection Committee
The Shaw Prize
28 May 2013 Hong Kong