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Michael Rosbash

michael rosbash, michael rosbash nobel prize
Michael Morris Rosbash born March 7, 1944 is an American geneticist and chronobiologist Rosbash is a professor at Brandeis University[1] 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[2] 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"[3][4]


  • 1 Life
  • 2 Research
    • 21 Chronology of major discoveries
    • 22 mRNA research
    • 23 Discovery of circadian TTFL in Drosophila
    • 24 Discovery of Drosophila Clock Gene
    • 25 Discovery of Drosophila Cycle Gene
    • 26 Discovery of cryptochrome as a Drosophila circadian photoreceptor
    • 27 LNV neurons as principal Drosophila circadian pacemaker
    • 28 Current research
  • 3 Positions
  • 4 Awards
  • 5 See also
  • 6 References
  • 7 External links


Michael Rosbash was born in Kansas City, Missouri His parents, Hilde and Alfred Rosbash, were Jewish refugees who left Nazi Germany in 1938[5][6] His father was a cantor, which, in Judaism, is a person who leads the congregation in prayer 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[7]


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[8] 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[9] 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[10] Also in May 1998, Rosbash et al discovered in Drosophila the clock gene cycle, a homolog of the mammalian bmal1 gene[11] In November 1998, Rosbash et al discovered the cryb Drosophila mutant, which lead to the conclusion that cryptochrome protein is involved in circadian photoreception[12]

Chronology of major discoveries

  • 1984: Cloned the Drosophila period gene
  • 1990: Proposed the Transcription Translation Negative Feedback Loop[2] for circadian clocks
  • 1998: Identified the Drosophila Clock Gene
  • 1998: Identified the Drosophila Cycle Gene
  • 1998: Identified cryptochrome as a Drosophila Circadian Photoreceptor
  • 1999: Identified LNV Neurons as the Principal Drosophila Circadian Pacemaker

mRNA research

Rosbash began studying mRNA processing as a graduate student at Massachusetts Institute of Technology His work in the Saccharomyces cerevisiae has revealed the enzymes, proteins, and subcellular organelles and their convergence upon mRNA in a specific order in order to translate mRNA into proteins Missteps in this process have been linked to diseases such as Alzheimer's disease, so this work is essential for better understanding and treatment of diseases[13]

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[2] that controls per mRNA levels, and that this transcription-translation feedback loop is a central feature of the Drosophila circadian clock[9]

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[9]

They transformed the period0 null mutation flies with a 72-kb piece of functional per DNA, and measured per mRNA levels at the per0 locus and new locus Following transformation, per mRNA levels were rhythmic at both the original and new locus The per0 locus was able to transcribe normal per mRNA and translate normal PER protein, meaning that rhythmicity was rescued by functional PER protein transcribed and translated from the 72-kb piece of per DNA There is a feedback loop at play in which cycling of PER protein levels at the new locus feeds back to dictate cycling of per mRNA levels at the original per0 locus[9] In 1992, Rosbash again collaborated with Jeffrey Hall and Paul Hardin to more closely examine the mechanisms of the TTFL They wondered specifically about the regulation of period mRNA level fluctuations, and found that per mRNA levels were transcriptionally regulated This was supported by the evidence that per precursor RNA cycles with the same phase as mature transcripts, and oscillate with respect to Zeitgeber Time ZT Other evidence for transcriptional regulation is that per gene promoter is sufficient to confer cycling to heterologous mRNA[14]

Discovery of Drosophila Clock Gene

A likely homolog of the previously discovered mouse gene Clock was identified by Rosbash et al by cloning of the Drosophila gene defined by the Jrk mutation This gene was given the name Drosophila Clock dClock has been shown to interact directly with the per and tim E-boxes and contributes to the circadian transcription of these genes The Jrk mutation disrupts the transcription cycling of per and tim It also results in completely arrhythmic behavior in constant darkness for homozygous mutants and about half demonstrated arrhythmic behavior in heterozygotes The Jrk homozygotes expressed low, non-cycling levels of per and tim mRNA as well as PER and TIM protein From this, it was concluded that the behavioral arrhythmicity in Jrk was due to a defect in the transcription of the per and tim This indicated that dClock was involved in the transcriptional activation of per and tim[10]

Discovery of Drosophila Cycle Gene

In 1998, Rosbash et al discovered the novel clock gene cycle, a homolog of the mammalian Bmal1 gene Homozygous cycle0 mutants are arrhythmic in locomotor activity and heterozygous cycle0/+ flies have robust rhythms with an altered period of rhythmicity Western blot analysis shows that homozygous cycle0 mutants have very little PER and TIM protein as well as low per and tim mRNA levels This indicates that lack of cycle leads to decreased transcription of per and tim genes Meiotic mapping placed cyc on the third chromosome They discovered bHLH-PAS domains in cyc, indicating protein binding and DNA binding functions[11]

Discovery of cryptochrome as a Drosophila circadian photoreceptor

In 1998, Rosbash et al discovered a Drosophila mutant exhibiting flat, non-oscillating levels of per and tim mRNA, due to a null mutation in the cryptochrome gene This mutation was dubbed crybaby, or cryb The failure of cryb mutants to synchronize to light dark cycles indicates that cryptochrome’s normal function involves circadian photoreception[12]

LNV neurons as principal Drosophila circadian pacemaker

In Drosophila, certain lateral neurons LNs have been shown to be important for circadian rhythms, including dorsal LNd and ventral LNV neurons LNV neurons express PDF pigment dispersion factor, which was initially hypothesized to be a clock output signal Mutants for the pdf neuropeptide gene pdf01 as well as flies selectively ablated for LNV produced similar behavioral responses Both entrained to external light cues, but were largely arrhythmic in constant conditions Some flies in each cases showed weak free-running rhythmicity These results lead the researchers to believe that LNV neurons were the critical circadian pacemaker neurons and that PDF was the principal circadian transmitter[15]

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, 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[16]

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[17]


  • Director of the Brandeis National Center for Behavioral Genomics[18]
  • The Inaugural Peter Gruber Endowed Chair in Neuroscience[19]
  • Co-Founder and Member of the Scientific Advisory Board of Hypnion, Inc[20]
  • Member, National Center for Sleep Disorders Advisory Panel of the NIH[21]
  • 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[22]
  • Helen Hay Whitney Fellow 1971–1974[23]
  • Fulbright Fellow 1965–1966[24]


  • Nobel Prize in Physiology or Medicine 2017[25]
  • 12th Annual Wiley Prize in Biomedical Sciences 2013[26]
  • Massry Prize 2012[27]
  • Canada Gairdner International Award 2012[28]
  • Louisa Gross Horwitz Prize from Columbia University 2011[24]
  • Gruber Prize in Neuroscience 2009[29]
  • Aschoff’s Rule 2008[29]
  • Caltech Distinguished Alumni Award 2001[30]
  • NIH Research Career Development Award 1976–1980[29]

See also

  • Circadian rhythm
  • Circadian clock
  • Period gene


  1. ^ "Life Sciences Faculty – Michael Rosbash" wwwbiobrandeisedu Retrieved 2 October 2017 
  2. ^ a b c "The Drosophila Molecular Clock Model – HHMI's BioInteractive" wwwhhmiorg Retrieved 2 October 2017 
  3. ^ Cha, Arlene Eujung 2017-10-02 "Nobel in physiology, medicine awarded to three Americans for discovery of 'clock genes'" Washington Post Retrieved 2017-10-02 
  4. ^ "The 2017 Nobel Prize in Physiology or Medicine – Press Release" The Nobel Foundation 2017-10-02 Retrieved 2017-10-02 
  5. ^ "Americans win Nobel medicine prize for circadian rhythm work" Retrieved 2 October 2017 
  6. ^ https://wwwfindagravecom/cgi-bin/fgcgipage=gr&GRid=132882242
  7. ^ "Michael Rosbash, PhD - HHMIorg" Retrieved 2 October 2017 
  8. ^ "Life Sciences Faculty – Jeffrey Hall, Emeritus" wwwbiobrandeisedu Retrieved 2 October 2017 
  9. ^ a b c d Hardin, P E; Hall, J C; Rosbash, M 1990 "Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels" Nature 343 6258: 536–540 doi:101038/343536a0 
  10. ^ a b Allada, R; White, N E; So, W V; Hall, J C; Rosbash, M 1998 "A Mutant Drosophila Homolog of Mammalian Clock Disrupts Circadian Rhythms and Transcription of period and timeless" Cell 93 5: 791–804 doi:101016/S0092-86740081440-3 
  11. ^ a b Rutila, J E; Suri, V; Le, M; So, W V; Rosbash, M 1998 "CYCLE Is a Second bHLH-PAS Clock Protein Essential for Circadian Rhythmicity and Transcription of Drosophila period and timeless" Cell 93 5: 805–814 doi:101016/S0092-86740081441-5 
  12. ^ a b Stanewsky, R; Kaneko, M; Emery, P; Beretta, B; Wager-Smith, K; Kay, S A; Rosbash, M; Hall, J C 1998 "The cryb Mutation Identifies Cryptochrome as a Circadian Photoreceptor in Drosophila" Cell 95 5: 681–682 doi:101016/S0092-86740081638-4 
  13. ^ "Michael Rosbash, PhD - HHMIorg" Retrieved 2 October 2017 
  14. ^ Hardin, P E; Hall, J C; Rosbash, M 1992 "Circadian oscillations in period gene mRNA levels are transcriptionally regulated" PNAS 89 24: 11711–11715 doi:101073/pnas892411711 PMC 50626  
  15. ^ Renn, S C P; Park, J H; Rosbash, M; Hall, J C; Taghert, P H 1999 "A pdf Neuropeptide Gene Mutation and Ablation of PDF Neurons Each Cause Severe Abnormalities of Behavioral Circadian Rhythms in Drosophila" Cell 99 7: 791–802 doi:101016/S0092-86740081676-1 
  16. ^ "Rosbash Lab" Rosbash Lab Retrieved 2 October 2017 
  17. ^ "Life Is an N of 1" Cell 171 6: 1241–1245 2017-11-30 doi:101016/jcell201711027 ISSN 0092-8674 
  18. ^ "National Center for Behavioral Genomics" wwwbiobrandeisedu Retrieved 2 October 2017 
  19. ^ "Rosbash receives new Gruber neuroscience chair – BrandeisNOW" BrandeisNOW Retrieved 2 October 2017 
  20. ^ "Hypnion, Inc: Board of Directors – Bloomberg" investingbusinessweekcom Retrieved 2 October 2017 
  21. ^ Colten, Harvey R; Altevogt, Bruce M; Research, Institute of Medicine US Committee on Sleep Medicine and 2 October 2017 "Sleep Disorders Research Advisory Board Membership" National Academies Press US Retrieved 2 October 2017 – via wwwncbinlmnihgov 
  22. ^ "John Simon Guggenheim Memorial Foundation Fellows" Retrieved 2 October 2017 [permanent dead link]
  23. ^ "Helen Hay Whitney Foundation Fellows" Archived from the original on 6 October 2015 Retrieved 2 October 2017 
  24. ^ a b "The Louisa Gross Horwitz Prize – Columbia University Medical Center" wwwcumccolumbiaedu 26 November 2013 Retrieved 2 October 2017 
  25. ^ Sample, Ian 2017-10-02 "Jeffrey C Hall, Michael Rosbash and Michael W Young win 2017 Nobel prize in physiology or medicine – as it happened" The Guardian ISSN 0261-3077 Retrieved 2017-10-02 
  26. ^ "Wiley: Twelfth Annual Wiley Prize in Biomedical Sciences Awarded to Dr Michael Young, Dr Jeffrey Hall and Dr Michael Rosbash" wwwwileycom Retrieved 2 October 2017 
  27. ^ Lebovits, Susan Chaityn 14 August 2012 "Rosbash awarded Massry for circadian rhythms work | BrandeisNOW" BrandeisNOW Retrieved 2017-10-02 
  28. ^ "Michael Rosbash – Gairdner Foundation" Retrieved 2 October 2017 
  29. ^ a b c "Society for Research on Biological Rhythms" Archived from the original on 25 February 2010 Retrieved 2 October 2017 
  30. ^ "California Institute of Technology Distinguished Alumni Awards" PDF Archived from the original PDF on 18 July 2012 Retrieved 2 October 2017 

External links

  • 2000 Holiday Lectures on Science – Clockwork Genes: Discoveries in Biological Time
  • Oscillatory Mechanisms Underlying the Drosophila Circadian Clock

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