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 Drosophila period gene in 1984 and proposed the Transcription Translation Negative Feedback Loop for circadian clocks in 1990. In 1998, they discovered the cycle gene, clock gene, and cryptochrome photoreceptor in Drosophila through the use of forward genetics, by first identifying the phenotype of a mutant and then determining the genetics behind the mutation. Rosbash was elected to the National Academy of Sciences in 2003. Along with Michael W. Young and Jeffrey C. Hall, he was awarded the 2017 Nobel Prize in Physiology or Medicine "for their discoveries of molecular mechanisms controlling the circadian rhythm".

Life Michael Rosbash was born in Kansas City, Missouri. His parents, Hilde and Alfred Rosbash, were Jewish refugees who left Nazi Germany in 1938. His father was a cantor, which, in Judaism, is a person who chants worship services. Rosbash's family moved to Boston when he was two years old, and he has been an avid Red Sox fan ever since.

Initially, Rosbash was interested in mathematics but an undergraduate biology course at the California Institute of Technology (Caltech) and a summer of working in Norman Davidson's lab steered him towards biological research. Rosbash graduated from Caltech in 1965 with a degree in chemistry, spent a year at the Institut de Biologie Physico-Chimique in Paris on the Fulbright Scholarship, and obtained a doctoral degree in biophysics in 1970 from the Massachusetts Institute of Technology under Sheldon Penman. After spending three years on a postdoctoral fellowship in genetics at the University of Edinburgh, Rosbash joined the Brandeis University faculty in 1974.

Rosbash is married to fellow scientist Nadja Abovich and he has a stepdaughter named Paula and daughter named Tanya.

Research Rosbash's research initially focused on the metabolism and processing of mRNA; mRNA is the molecular link between DNA and protein. After arriving at Brandeis, Rosbash collaborated with co-worker Jeffrey Hall and investigated the genetic influences on circadian rhythms of the internal biological clock. They used Drosophila melanogaster to study patterns of activity and rest. In 1984, Rosbash and Hall cloned the first Drosophila clock gene, period. Following work done by post-doctoral fellow, Paul Hardin, in discovering that period mRNA and its associated protein (PER) had fluctuating levels during the circadian cycle, in 1990 they proposed a Transcription Translation Negative Feedback Loop (TTFL) model as the basis of the circadian clock. Also in May 1998, Rosbash et al. discovered in Drosophila the clock gene cycle, a homolog of the mammalian bmal1 gene. In November 1998, Rosbash et al. discovered the cryb Drosophila mutant, which led to the conclusion that cryptochrome protein is involved in circadian photoreception.

Chronology of major discoveries 1984: Cloned the Drosophila period gene 1990: Proposed the Transcription Translation Negative Feedback Loop

Discovery of circadian TTFL in Drosophila In 1990, Rosbash, Hall, and Hardin discovered the role of the period gene (per) in the Drosophila''' circadian oscillator. They found that PER protein levels fluctuate in light dark cycles, and these fluctuations persist in constant darkness. Similarly, per mRNA abundance also has rhythmic expression that entrains to light dark cycles. In the fly head, per mRNA levels oscillate in both 12-hour light, 12-hour dark cycles as well as in constant darkness. Per mRNA levels peaked at the beginning of the subjective night followed by a peak in PER protein levels about 6 hours later. Mutated per genes affected the cycling of per mRNA. From this experimental data, Rosbash, Hall, and Hardin hypothesized that PER protein is involved in a negative feedback loop

They also looked at two other single missense period mutations, perS and perL1. These mutations cause the peak of the evening activity to occur earlier and later, respectively, compared to wildtype per+ flies. They found that RNA levels for perS and perL1 also display clear rhythmicity. Like locomotor activity the peak expression is shifted earlier for perS and later for perL1.

Challenges to the TTFL model in Drosophila The Akhilesh Reddy group has shown, using a range of unbiased -omics techniques (RNA-sequencing, proteomics, metabolomics) that Drosophila S2 cells display circadian molecular rhythms. These cells do not express known "clock genes" including per and tim. Introduction of PER and TIM proteins into the cells does not cause rhythmicity of these cells as read out by abundance or phosphorylation of PER and TIM proteins. These cells were thus regarded as "clock-less" by the fly field until now.

Current research In more recent years, Rosbash has been working on the brain-neuronal aspects of circadian rhythms. Seven anatomically distinct neuronal groups have been identified that all express the core clock genes. However, the mRNAs appear to be expressed in a circadian and neuron-specific manner, for which his lab has taken interest in determining whether this provides a link to the distinct functions of certain neuronal groups. He has also researched the effects of light on certain neuronal groups and has found that one subgroup is light-sensitive to lights on (dawn) and another is light-sensitive to lights off (dusk). The dawn cells have been shown to promote arousal while the dusk cells promote sleep.

Today, Rosbash continues to research mRNA processing and the genetic mechanisms underlying circadian rhythms. He has also published an amusing reflection on his life in science.

Positions Director of the Brandeis National Center for Behavioral Genomics The Inaugural Peter Gruber Endowed Chair in Neuroscience Co-Founder and Member of the Scientific Advisory Board of Hypnion, Inc. Member, National Center for Sleep Disorders Advisory Panel of the NIH Member, Center for Biological Timing of the NSF Howard Hughes Medical Institute Investigator (1989–present) Fellow, American Association for the Advancement of Science (2007) Member, National Academy of Sciences (2003) Member, American Academy of Arts and Sciences (1997) Guggenheim Fellow (1989–1990) Helen Hay Whitney Fellow (1971–1974) Fulbright Fellow (1965–1966)

Awards Nobel Prize in Physiology or Medicine (2017) 12th Annual Wiley Prize in Biomedical Sciences (2013) Massry Prize (2012) Canada Gairdner International Award (2012) Louisa Gross Horwitz Prize from Columbia University (2011) Aschoff's Rule (2008) NIH Research Career Development Award (1976–1980)