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| accessdate = 9 January 2012}}</ref>
| accessdate = 9 January 2012}}</ref>
*In 2012, Reppert and colleagues established [http://monarchbase.umassmed.edu/ MonarchBase], an integrated database for Danaus plexippus' genome. The goal of the project was to make genomic and proteomic information about monarch butterflies accessible to biological and lepidopteran communities. <ref>{{cite journal|last=Zhan|first=S|coauthors=Reppert SM|title=MonarchBase: the monarch butterfly genome database.|journal=Nucleic Acids Research Advance Access|date=9|year=2012|month=November|pages=1-6}}</ref>
*In 2012, Reppert and colleagues established [http://monarchbase.umassmed.edu/ MonarchBase], an integrated database for Danaus plexippus' genome. The goal of the project was to make genomic and proteomic information about monarch butterflies accessible to biological and lepidopteran communities. <ref>{{cite journal|last=Zhan|first=S|coauthors=Reppert SM|title=MonarchBase: the monarch butterfly genome database.|journal=Nucleic Acids Research Advance Access|date=9|year=2012|month=November|pages=1-6}}</ref>
*The monarch clockwork model, which has both drosophila-like and mammalian-like aspects, is unique because it utilizes two distinct CRYPTOCHROME (CRY) proteins. As presented in a 2010 paper<ref>{{cite journal|last=Reppert|first=SM|coauthors=Gegear R, Merlin C|title=Navigational mechanisms of migrating monarch butterflies|journal=Trends in Neurosciences|year=2010|month=September|volume=33|pages=391-434}}</ref> , operates as follows:
**There is an autoregulatory transcription feedback loop in which heterodimers of CLOCK (CLK) and CYCLE (CYC) form and drive the transcription of the period (per), timeless (tim), and cryptochrome2 (cry2) genes;
**TIM (T), PER (P), and CRY2 (C2) proteins are translated and move from the nucleus to the cytoplasm where they form complexes;
**24 hours later CRY2 returns to the nucleus, inhibiting CLK:CYC transcription;
**Meanwhile PER is progressively phosphorylated, which may aid CRY2 translocation into the nucleus;
** And CRYPTOCHROME1 (CRY1, C1) protein is a circadian photoreceptor which when exposed to light, causes TIM degradation, allowing light to gain access to the central clock mechanism for photic entrainment.


His laboratory also provided the first genetic evidence that animal cryptochromes can function as light-dependent [[magnetoreception|magnetoreceptors]],<ref name="pmid18641630">
His laboratory also provided the first genetic evidence that animal cryptochromes can function as light-dependent [[magnetoreception|magnetoreceptors]],<ref name="pmid18641630">

Revision as of 19:17, 13 April 2013

Steven M. Reppert is an American neuroscientist who is known for his contributions to the fields of circadian biology and neuroethology. His research has focused largely on the physiological, cellular, and molecular basis of circadian rhythms in mammals and more recently on the navigational mechanisms of migratory monarch butterflies. He is currently the founding chair of the Department of Neurobiology and the Higgins Family Professor of Neuroscience at the University of Massachusetts Medical School.

Photo of Steven Reppert.
The Wikipede edits Steven Reppert.

Background

Reppert received his BS and MD (with Distinction) from the University of Nebraska College of Medicine and was elected as a medical student to the Alpha Omega Alpha Honor Medical Society. He did an internship and residency in Pediatrics at the Massachusetts General Hospital and postdoctoral work in neuroendocrinology at the National Institute of Child Health and Human Development in Bethesda, Maryland with David C. Klein. Reppert was on the faculty at the Massachusetts General Hospital and Harvard Medical School beginning in 1979 and was promoted to Professor in 1993; he directed the Laboratory of Developmental Chronobiology at the Massachusetts General Hospital from 1983 to 2001, when he moved to the University of Massachusetts Medical School.[1]

Reppert was a Charles King Trust Research Fellow from 1981 to 1983 and an Established Investigator of the American Heart Association from 1985 to 1990. He has been a recipient of the E. Mead Johnson Award for Outstanding Research Contributions (1989)[2] and the NIH-NICHD MERIT Award (1992–2002). From 2002 to 2004, he served as president of the Society for Research on Biological Rhythms.[3] He is an elected fellow of the American Association for the Advancement of Science.[4] Reppert has published more than 150 papers in peer-reviewed journals and is the principal inventor on seven patents derived from his research.[5]

Research

The research contributions of Reppert and colleagues include defining the field of fetal circadian clocks,[6][7][8] discovering that the circadian clock mechanism in the mammalian suprachiasmatic nucleus (SCN), the site of the master brain clock, is cell autonomous (i.e., contained within single cells),[9][10] and cloning and functionally defining a family of melatonin receptors (G-protein coupled receptors for the pineal hormone).[11][12] Reppert’s group identified a molecular mechanism for regulating clock-controlled genes in mammals,[13] discovered the function of cryptochromes within the mammalian circadian clock,[14][15] and defined interlocking transcriptional feedback loops in the mouse SCN.[16][17] In 2006, his team made the unexpected finding that CLOCK, a transcription factor believed to be an essential component of the molecular clockwork mechanism, is not necessary for SCN clock function.[18][19][20] They went on to show that a related transcription factor, NPAS2 (MOP4), can functionally substitute for CLOCK in the SCN[21][22] to regulate behavioral circadian rhythms.

Monarch Butterfly Migration Research

Since 2002, Reppert and co-workers have pioneered study of the biological basis of monarch butterfly migration.[23][24] They have focused on a novel circadian clock mechanism and its role in time-compensated sun compass orientation, a major navigational strategy the butterflies use during their fall migration.[23][25] Steven Reppert's lab has published numerous papers detailing their findings:

  • Using previous electrophysiological studies of locusts, as well as careful mapping of the monarch butterflies brain, Reppert has indicated that the “central complex (CX) is likely the site of the actual sun compass.” [26]
  • His group has shown that antennae are necessary for this strategy, and that they house circadian clocks that function independent from the brain.[27]

[28] [29]

  • Reppert’s lab expanded upon the previous postulations of Fred Urquhart which stated that antennae may play a role in monarch migration. In 2009 Reppert’s lab reported that, despite previous assumptions that the clock is located in the brain, there actually are antennal clocks, and “the antennae are necessary for proper time-compensated sun compass orientation in migratory monarch butterflies.” [30]
  • In 2011, Reppert and colleagues presented the initial draft sequence of the monarch butterfly genome and a set 16,866 protein-coding genes. This is the first characterized genome of a butterfly and of a long-distance migratory species.[31][32][33]
  • In 2012, Reppert and colleagues established MonarchBase, an integrated database for Danaus plexippus' genome. The goal of the project was to make genomic and proteomic information about monarch butterflies accessible to biological and lepidopteran communities. [34]
  • The monarch clockwork model, which has both drosophila-like and mammalian-like aspects, is unique because it utilizes two distinct CRYPTOCHROME (CRY) proteins. As presented in a 2010 paper[35] , operates as follows:
    • There is an autoregulatory transcription feedback loop in which heterodimers of CLOCK (CLK) and CYCLE (CYC) form and drive the transcription of the period (per), timeless (tim), and cryptochrome2 (cry2) genes;
    • TIM (T), PER (P), and CRY2 (C2) proteins are translated and move from the nucleus to the cytoplasm where they form complexes;
    • 24 hours later CRY2 returns to the nucleus, inhibiting CLK:CYC transcription;
    • Meanwhile PER is progressively phosphorylated, which may aid CRY2 translocation into the nucleus;
    • And CRYPTOCHROME1 (CRY1, C1) protein is a circadian photoreceptor which when exposed to light, causes TIM degradation, allowing light to gain access to the central clock mechanism for photic entrainment.

His laboratory also provided the first genetic evidence that animal cryptochromes can function as light-dependent magnetoreceptors,[36][37] which may be important for long-distance migration.[38]

References

  1. ^ http://www.umassmed.edu/neuroscience/faculty/reppert.cfm
  2. ^ http://www.aps-spr.org/spr/Awards/EMJ.htm
  3. ^ http://www.srbr.org/Pages/past_meetings.aspx
  4. ^ http://www.aaas.org/aboutaaas/fellows/
  5. ^ http://www.patentbuddy.com/Inventor/Reppert-Steven-M/1437735
  6. ^ Reppert SM, Schwartz WJ (1983). "Maternal coordination of the fetal biological clock in utero". Science. 220 (4600): 969–71. doi:10.1126/science.6844923. PMID 6844923. {{cite journal}}: Unknown parameter |month= ignored (help)
  7. ^ "Scientists find unborn rats can sense time". Lawrence, KS: Lawrence Journal-World. Associated Press. May 20, 1983. p. 23.
  8. ^ Klinkenborg, Verlyn (5 January 1997). "Awakening to Sleep". The New York Times Magazine. New York.
  9. ^ Welsh DK, Logothetis DE, Meister M, Reppert SM (1995). "Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms". Neuron. 14 (4): 697–706. doi:10.1016/0896-6273(95)90214-7. PMID 7718233. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  10. ^ Caldwell, Mark (July 1999). "Mind Over Time". DISCOVER Magazine. Retrieved 12 January 2010.
  11. ^ Reppert SM, Weaver DR, Godson C (1996). "Melatonin receptors step into the light: cloning and classification of subtypes". Trends in Pharmacological Sciences. 17 (3): 100–2. doi:10.1016/0165-6147(96)10005-5. PMID 8936344. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  12. ^ Barinaga M (1997). "How jet-lag hormone does double duty in the brain". Science. 277 (5325): 480. doi:10.1126/science.277.5325.480. PMID 9254421. {{cite journal}}: Unknown parameter |month= ignored (help)
  13. ^ Jin X, Shearman LP, Weaver DR, Zylka MJ, de Vries GJ, Reppert SM (1999). "A molecular mechanism regulating rhythmic output from the suprachiasmatic circadian clock". Cell. 96 (1): 57–68. doi:10.1016/S0092-8674(00)80959-9. PMID 9989497. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  14. ^ Kume K, Zylka MJ, Sriram S; et al. (1999). "mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop". Cell. 98 (2): 193–205. doi:10.1016/S0092-8674(00)81014-4. PMID 10428031. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  15. ^ Barinaga M (1999). "Circadian rhythms. CRY's clock role differs in mice, flies". Science. 285 (5427): 506–7. doi:10.1126/science.285.5427.506. PMID 10447476. {{cite journal}}: Unknown parameter |month= ignored (help)
  16. ^ Shearman LP, Sriram S, Weaver DR; et al. (2000). "Interacting molecular loops in the mammalian circadian clock". Science. 288 (5468): 1013–9. doi:10.1126/science.288.5468.1013. PMID 10807566. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  17. ^ Barinaga M (2000). "Circadian rhythms. Two feedback loops run mammalian clock". Science. 288 (5468): 943–4. doi:10.1126/science.288.5468.943a. PMID 10841707. {{cite journal}}: Unknown parameter |month= ignored (help)
  18. ^ Debruyne JP, Noton E, Lambert CM, Maywood ES, Weaver DR, Reppert SM. (2006). "A clock shock: mouse CLOCK is not required for circadian oscillator function". Neuron. 50 (3): 465–77. doi:10.1016/j.neuron.2006.03.041. PMID 16675400. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  19. ^ Collins B, Blau J. (2006). "Keeping Time without a Clock". Neuron. 50 (3): 348–50. doi:10.1016/j.neuron.2006.04.022. PMID 16675389. {{cite journal}}: Unknown parameter |month= ignored (help)
  20. ^ Miller G (2006). "Despite Mutated Gene, Mouse Circadian Clock Keeps on Ticking". Science. 312 (5774): 673. doi:10.1126/science.312.5774.673. PMID 16675672. {{cite journal}}: Unknown parameter |month= ignored (help)
  21. ^ DeBruyne JP, Weaver DR, Reppert SM. (2007). "CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock". Nat Neurosci. 10 (5): 543–5. doi:10.1038/nn1884. PMC 2782643. PMID 17417633. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  22. ^ Asher G, Schibler U. (2006). "A CLOCK-less clock". Trends Cell Biol. 16 (11): 547–9. doi:10.1016/j.tcb.2006.09.005. PMID 16996737. {{cite journal}}: Unknown parameter |month= ignored (help)
  23. ^ a b Kyriacou CP (2009). "Clocks, cryptochromes and Monarch migrations". Journal of Biology. 8 (6): 55. doi:10.1186/jbiol153. PMC 2737371. PMID 19591650.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  24. ^ Reppert SM, Gegear RJ, Merlin C (2010). "Navigational mechanisms of migrating monarch butterflies". Trends in Neurosciences. 33 (9): 399–406. doi:10.1016/j.tins.2010.04.004. PMC 2929297. PMID 20627420.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  25. ^ Hotz, Robert Lee (8 February 2008). "Using Butterfly Time, We Can Learn Secrets Of Our Own 'Clocks'". The Wall Street Journal. New York. pp. B1.
  26. ^ Heinze, S (2013). "Anatomical basis of sun compass navigation II: The neuronal composition of the central complex of the monarch butterfly". Comp Neurol. 521: 267-298. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  27. ^ Merlin C, Gegear RJ, Reppert SM (2009). "Antennal circadian clocks coordinate sun compass orientation in migratory monarch butterflies". Science. 325 (5948): 1700–4. doi:10.1126/science.1176221. PMC 2754321. PMID 19779201. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  28. ^ Kyriacou CP (2009). "Physiology. Unraveling traveling". Science. 325 (5948): 1629–30. doi:10.1126/science.1178935. PMID 19779177. {{cite journal}}: Unknown parameter |month= ignored (help)
  29. ^ Buchen, Lizzie (2009). "Butterflies' migrational timekeeper found". Nature. doi:10.1038/news.2009.946.
  30. ^ Guerra, P (2012). "Discordant timing between antennae disrupts sun compass orientation in migratory monarch butterflies". Nat Commun. 3: 958. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  31. ^ Zhan S, Merlin C, Boore JL, Reppert SM (2011). "The Monarch Butterfly Genome Yields Insights into Long-Distance Migration". Cell. 147 (5): 1171–85. doi:10.1016/j.cell.2011.09.052. PMID 22118469. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  32. ^ Stensmyr MC, Hansson BS (2011). "A Genome Befitting a Monarch". Cell. 147 (5): 970–2. doi:10.1016/j.cell.2011.11.009. PMID 22118454. {{cite journal}}: Unknown parameter |month= ignored (help)
  33. ^ Johnson, Carolyn Y. (23 November 2011). "Monarch butterfly genome sequenced". The Boston Globe. Boston, MA. Retrieved 9 January 2012.
  34. ^ Zhan, S (9). "MonarchBase: the monarch butterfly genome database". Nucleic Acids Research Advance Access: 1–6. {{cite journal}}: Check date values in: |date= and |year= / |date= mismatch (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  35. ^ Reppert, SM (2010). "Navigational mechanisms of migrating monarch butterflies". Trends in Neurosciences. 33: 391–434. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  36. ^ Gegear RJ, Casselman A, Waddell S, Reppert SM (2008). "Cryptochrome mediates light-dependent magnetosensitivity in Drosophila". Nature. 454 (7207): 1014–8. doi:10.1038/nature07183. PMC 2559964. PMID 18641630. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  37. ^ Rouyer F (2008). "Physiology: Mutant flies lack magnetic sense". Nature. 454 (7207): 949–51. doi:10.1038/454949a. PMID 18719575. {{cite journal}}: Unknown parameter |month= ignored (help)
  38. ^ Gray, Richard (27 June 2010). "Monarch butterflies use internal compass to find their way". The Daily Telegraph. UK.

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