2017 Nobel Prize in Physiology or Medicine jointly to Jeffrey C. Hall (ex-Brandeis, University of Maine), Michael Rosbash (Brandeis University) and Michael W. Young (Rockefeller University in New York) for their discoveries of molecular mechanisms controlling the circadian rhythm
Curator: Aviva Lev-Ari, PhD, RN

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Press Release
2017-10-02
The Nobel Assembly at Karolinska Institutet has today decided to award
the 2017 Nobel Prize in Physiology or Medicine
jointly to
Jeffrey C. Hall, Michael Rosbash and Michael W. Young
for their discoveries of molecular mechanisms controlling the circadian rhythm
READ the Summary
https://www.nobelprize.org/nobel_prizes/medicine/laureates/2017/press.html
Jeffrey C. Hall was born 1945 in New York, USA. He received his doctoral degree in 1971 at the University of Washington in Seattle and was a postdoctoral fellow at the California Institute of Technology in Pasadena from 1971 to 1973. He joined the faculty at Brandeis University in Waltham in 1974. In 2002, he became associated with University of Maine.
Michael Rosbash was born in 1944 in Kansas City, USA. He received his doctoral degree in 1970 at the Massachusetts Institute of Technology in Cambridge. During the following three years, he was a postdoctoral fellow at the University of Edinburgh in Scotland. Since 1974, he has been on faculty at Brandeis University in Waltham, USA.
Michael W. Young was born in 1949 in Miami, USA. He received his doctoral degree at the University of Texas in Austin in 1975. Between 1975 and 1977, he was a postdoctoral fellow at Stanford University in Palo Alto. From 1978, he has been on faculty at the Rockefeller University in New York.
Key publications
Zehring, W.A., Wheeler, D.A., Reddy, P., Konopka, R.J., Kyriacou, C.P., Rosbash, M., and Hall, J.C. (1984). P-element transformation with period locus DNA restores rhythmicity to mutant, arrhythmic Drosophila melanogaster. Cell 39, 369–376.
Bargiello, T.A., Jackson, F.R., and Young, M.W. (1984). Restoration of circadian behavioural rhythms by gene transfer in Drosophila. Nature 312, 752–754.
Siwicki, K.K., Eastman, C., Petersen, G., Rosbash, M., and Hall, J.C. (1988). Antibodies to the period gene product of Drosophila reveal diverse tissue distribution and rhythmic changes in the visual system. Neuron 1, 141–150.
Hardin, P.E., Hall, J.C., and Rosbash, M. (1990). Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels. Nature 343, 536–540.
Liu, X., Zwiebel, L.J., Hinton, D., Benzer, S., Hall, J.C., and Rosbash, M. (1992). The period gene encodes a predominantly nuclear protein in adult Drosophila. J Neurosci 12, 2735–2744.
Vosshall, L.B., Price, J.L., Sehgal, A., Saez, L., and Young, M.W. (1994). Block in nuclear localization of period protein by a second clock mutation, timeless. Science 263, 1606–1609.
Price, J.L., Blau, J., Rothenfluh, A., Abodeely, M., Kloss, B., and Young, M.W. (1998). double-time is a novel Drosophila clock gene that regulates PERIOD protein accumulation. Cell 94, 83–95.
Keeping time on our human physiology
The biological clock is involved in many aspects of our complex physiology. We now know that all multicellular organisms, including humans, utilize a similar mechanism to control circadian rhythms. A large proportion of our genes are regulated by the biological clock and, consequently, a carefully calibrated circadian rhythm adapts our physiology to the different phases of the day (Figure 3). Since the seminal discoveries by the three laureates, circadian biology has developed into a vast and highly dynamic research field, with implications for our health and wellbeing.

Figure 3. The circadian clock anticipates and adapts our physiology to the different phases of the day. Our biological clock helps to regulate sleep patterns, feeding behavior, hormone release, blood pressure, and body temperature.
SOURCE
https://www.nobelprize.org/nobel_prizes/medicine/laureates/2017/press.html
Medicine Nobel awarded for work on circadian clocks, Jeffrey Hall, Michael Rosbash and Michael Young unpicked molecular workings of cells’ daily rhythms.
02 October 2017
Other Related Research
Mammalian Circadian Clocks
Circadian clocks are molecular oscillators with ~24-hour periods that drive daily biological rhythms. Such clocks are found in all of the major branches of life, and they likely represent ancient timekeeping systems important for predicting daily environmental cycles on our rotating planet. In mammals, circadian clocks are present in most if not all cells. These distributed clocks control a myriad of processes, in aggregate creating coherent 24-hour programs of physiology and behavior.
A picture of how circadian clocks are built has emerged in the last two decades. The core mechanism is a transcriptional feedback loop, wherein the protein products of several clock genes build the molecular machinery to inhibit the transcription factor responsible for their own production. The molecular components of circadian clocks are conserved from insects to humans.
The Weitz lab uses molecular biology, biochemistry, genetics, and structural biology to investigate the mammalian circadian clock. The focus of our efforts at present is to understand the circadian clock in terms of the integrated functions of its several multi-protein machines. This effort is principally based on the purification of endogenous circadian clock protein complexes from mouse tissues and their biochemical analysis and structural study by cryo-electron microscopy.

Fig. 1. Class-average electron microscopy images of the mouse nuclear PER complex, a core circadian clock machine. It is a 1.9-MDa assembly of about thirty proteins that appears as a quasi-spherical, beaded particle of 40-nm diameter. Our current work provides an initial low-resolution view of the structural organization of endogenous clock machinery from a eukaryote. We aim to obtain high-resolution structures.
Selected papers:
Duong HA, Robles MS, Knutti K, Weitz CJ. A molecular mechanism for circadian clock negative feedback. Science 332, 1436-1439 (2011).
Padmanabhan K, Robles MS, Westerling T, Weitz CJ. Feedback regulation of transcriptional termination by the mammalian circadian clock PERIOD complex. Science 337, 599-602 (2012).
Kim JY, Kwak PB, Weitz CJ. Specificity in circadian clock feedback from targeted reconstitution of the NuRD co-repressor. Mol. Cell 56, 738-748 (2014).
Aryal RA, Kwak PB, Tamayo AG, Chiu PL, Walz T, Weitz CJ. Macromolecular assemblies of the mammalian circadian clock. Mol. Cell (2017, in press).
SOURCE
http://neuro.hms.harvard.edu/people/faculty/charles-weitz
Circadian Clock’s Inner Gears

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