MICHAEL ROSBASH

                                                    MICHAEL ROSBASH

       Michael Morris Rosbash:-  born March 7, 1944 is an American geneticist and chronobiologist. Rosbash is a professor 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

          Rosbash’s research initially focused on the metabolism and processing of mRNA; mRNA is the molecular link between DNAand 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. Following this proposal, they looked into the elements that make up other parts of the clock. In May 1998, Rosbash et al. found a homolog for mammalian Clock that performed the same function of activating the transcription of per and tim that they proceeded to call dClock. 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 cry Drosophila mutant, which lead to the conclusion that cryptochrome protein is involved in circadian photoreception.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 that controls per mRNA levels, and that this transcription-translation feedback loop is a central feature of the Drosophila circadian clock.