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    Patrick Emery PhD

    TitleProfessor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentNeurobiology
    AddressUniversity of Massachusetts Medical School
    364 Plantation Street, LRB-726
    Worcester MA 01605
    Phone508-856-6599
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMD/PhD Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentNeuroscience

        Overview 
        Narrative

        Mailing Address:
        Patrick Emery, Ph.D
        University of Massachusetts Medical School

        Department of Neurobiology, LRB-726
        364 Plantation Street,
        Worcester, MA 01605 USA
        e-mail: patrick.emery@umassmed.edu

        Academic Background

        Maturité scientifique. Collège Rousseau, Geneva 1987
        Degree in Biology, University of Geneva 1990
        Diploma in Molecular Biology,
        U of Geneva Medical School
        1991
        PhD, U of Geneva Medical School 1996
        Postdoctoral Fellow, Brandeis University 1997-2001
        Research Fellowships,
        Swiss National Science Foundation
        1997-2000


        Patrick's Photo

        Circadian Rhythms and their Synchronization in Drosophila

        Drosophila melanogaster is a powerful model organism for understanding the genetic, molecular and neural bases of animal behaviors. Circadian rhythms are a prime example of behaviors whose molecular and neural foundations have been greatly increased by studies in Drosophila. A biological clock dictates that animals sleep and wake with a ca. 24-hour period, and this is true even when they are kept under constant conditions, without any information from the environment. Using genetic screens, many essential clock proteins (e.g. PER, TIM, figure 1) were identified in Drosophila. It has been shown that homologues of most of these proteins are also involved in generating mammalian circadian rhythms. Human homologues of Drosophila PER (hPER2) and DBT (hCK-Id) are actually mutated in patients with advanced sleep-phase syndrome. This demonstrates that the discoveries made in Drosophila are playing a crucial role in understanding human circadian behavior.

        The Drosophila circadian pacemaker is a transcriptional feedback loop (fig.1), in which PER and TIM negatively regulate their own transcription.  Kinases and phosphatases determine the pace of this feedback loop by controlling PER and TIM phosphorylation, and hence their stability and repressive activity. Recent studies, including work from our lab, show that at least in circadian pacemaker neurons (the small ventral lateral neurons, fig.2) translational control of the key pacemaker protein PER is also critical for 24-hour period behavioral rhythms.  Ataxin-2 - whose mammalian homolog is involved in various neurodegenerative diseases – promotes PER translation with the help of the translational factor TYF.  A major objective of our lab is thus to understand the mechanisms by which Ataxin-2, and more generally RNA binding proteins, control circadian rhythms.   

        The other major goal of our lab is to discover the mechanisms by which circadian rhythms are synchronized with the day/night cycle.  These mechanisms are critical, since the period of circadian rhythms only approximates 24 hours, and day length changes at most latitudes over the course of the year.  We are thus elucidating the cell-autonomous molecular mechanisms by which light and temperature inputs synchronize circadian molecular pacemakers.  Interestingly, it has recently become clear that communication between circadian neurons is also critical to properly synchronize circadian behavior.  Therefore, we also study the circadian neurons that detect light and temperature inputs, and determine how these neurons communicate with the rest of the circadian neural network. Our ultimate goal is to understand how different environmental inputs are integrated to optimize daily animal physiology and behavior.

        Figures

        Fig.1:  The circadian pacemaker is a transcriptional feedback loop.  It is synchronized with light by the intracellular photoreceptor CRY, which binds to TIM and triggers its proteasome degradation, mediated by JET. 

         

        Fig.2:  The small ventral Lateral Neurons (left) are critical pacemaker neurons driving circadian behavior.  Knocking down ATX2 in these cells lengthen circadian behavioral rhythms to ca. 26.5 hr instead of 24hr



        Rotation Projects

        Potential Rotation Projects

        Circadian clocks play an essential role in the temporal organization of animal physiology and behavior.Proper synchronization of these clocks with the day/night cycle is essential for their function. We combine the powerful genetics of Drosophila with molecular, cell culture and behavioral approaches to obtain a comprehensive view of the mechanisms regulating circadian rhythms and their synchronization.

        Rotation projects could for example focus on the mechanisms of signal transduction in the CRY light input pathway, on the molecular mechanisms underlying circadian temperature responses, or on characterizing the neural network controlling the synchronization of circadian behavior with light and temperature cycles.



        Post Docs

        A postdoc position is available to study circadian rhythms in Drosophila.  Contact Patrick Emery (patrick.emery@umassmed.edu).



        Bibliographic 
        selected publications
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        1. Lamba P, Bilodeau-Wentworth D, Emery P, Zhang Y. Morning and evening oscillators cooperate to reset circadian behavior in response to light input. Cell Rep. 2014 May 8; 7(3):601-8.
          View in: PubMed
        2. Tataroglu O, Emery P. Studying circadian rhythms in Drosophila melanogaster. Methods. 2014 Jun 15; 68(1):140-50.
          View in: PubMed
        3. Zhang Y, Ling J, Yuan C, Dubruille R, Emery P. A role for Drosophila ATX2 in activation of PER translation and circadian behavior. Science. 2013 May 17; 340(6134):879-82.
          View in: PubMed
        4. Karpowicz P, Zhang Y, Hogenesch JB, Emery P, Perrimon N. The circadian clock gates the intestinal stem cell regenerative state. Cell Rep. 2013 Apr 25; 3(4):996-1004.
          View in: PubMed
        5. Zhang Y, Emery P. GW182 controls Drosophila circadian behavior and PDF-receptor signaling. Neuron. 2013 Apr 10; 78(1):152-65.
          View in: PubMed
        6. Ling J, Dubruille R, Emery P. KAYAK-a modulates circadian transcriptional feedback loops in Drosophila pacemaker neurons. J Neurosci. 2012 Nov 21; 32(47):16959-70.
          View in: PubMed
        7. Emery P. Circadian rhythms: An electric jolt to the clock. Curr Biol. 2012 Oct 23; 22(20):R876-8.
          View in: PubMed
        8. Kaneko H, Head LM, Ling J, Tang X, Liu Y, Hardin PE, Emery P, Hamada FN. Circadian rhythm of temperature preference and its neural control in Drosophila. Curr Biol. 2012 Oct 9; 22(19):1851-7.
          View in: PubMed
        9. Zhang Y, Liu Y, Bilodeau-Wentworth D, Hardin PE, Emery P. Light and temperature control the contribution of specific DN1 neurons to Drosophila circadian behavior. Curr Biol. 2010 Apr 13; 20(7):600-5.
          View in: PubMed
        10. Dubruille R, Murad A, Rosbash M, Emery P. A constant light-genetic screen identifies KISMET as a regulator of circadian photoresponses. PLoS Genet. 2009 Dec; 5(12):e1000787.
          View in: PubMed
        11. Dubruille R, Emery P. A plastic clock: how circadian rhythms respond to environmental cues in Drosophila. Mol Neurobiol. 2008 Oct; 38(2):129-45.
          View in: PubMed
        12. Emery P, Francis M. Circadian rhythms: timing the sense of smell. Curr Biol. 2008 Jul 8; 18(13):R569-71.
          View in: PubMed
        13. Zhu H, Sauman I, Yuan Q, Casselman A, Emery-Le M, Emery P, Reppert SM. Cryptochromes define a novel circadian clock mechanism in monarch butterflies that may underlie sun compass navigation. PLoS Biol. 2008 Jan; 6(1):e4.
          View in: PubMed
        14. Busza A, Murad A, Emery P. Interactions between circadian neurons control temperature synchronization of Drosophila behavior. J Neurosci. 2007 Oct 3; 27(40):10722-33.
          View in: PubMed
        15. Emery P, Freeman MR. Glia got rhythm. Neuron. 2007 Aug 2; 55(3):337-9.
          View in: PubMed
        16. Kaushik R, Nawathean P, Busza A, Murad A, Emery P, Rosbash M. PER-TIM interactions with the photoreceptor cryptochrome mediate circadian temperature responses in Drosophila. PLoS Biol. 2007 Jun; 5(6):e146.
          View in: PubMed
        17. Murad A, Emery-Le M, Emery P. A subset of dorsal neurons modulates circadian behavior and light responses in Drosophila. Neuron. 2007 Mar 1; 53(5):689-701.
          View in: PubMed
        18. Emery P. RNA extraction from Drosophila heads. Methods Mol Biol. 2007; 362:305-7.
          View in: PubMed
        19. Emery P. Protein extraction from Drosophila heads. Methods Mol Biol. 2007; 362:375-7.
          View in: PubMed
        20. Emery P. Mutagenesis with Drosophila. Methods Mol Biol. 2007; 362:187-95.
          View in: PubMed
        21. Emery P. RNase protection assay. Methods Mol Biol. 2007; 362:343-8.
          View in: PubMed
        22. Rush BL, Murad A, Emery P, Giebultowicz JM. Ectopic CRYPTOCHROME renders TIM light sensitive in the Drosophila ovary. J Biol Rhythms. 2006 Aug; 21(4):272-8.
          View in: PubMed
        23. Emery P, Reppert SM. A rhythmic Ror. Neuron. 2004 Aug 19; 43(4):443-6.
          View in: PubMed
        24. Martin G, Puig S, Pietrzykowski A, Zadek P, Emery P, Treistman S. Somatic localization of a specific large-conductance calcium-activated potassium channel subtype controls compartmentalized ethanol sensitivity in the nucleus accumbens. J Neurosci. 2004 Jul 21; 24(29):6563-72.
          View in: PubMed
        25. Busza A, Emery-Le M, Rosbash M, Emery P. Roles of the two Drosophila CRYPTOCHROME structural domains in circadian photoreception. Science. 2004 Jun 4; 304(5676):1503-6.
          View in: PubMed
        26. Zhao J, Kilman VL, Keegan KP, Peng Y, Emery P, Rosbash M, Allada R. Drosophila clock can generate ectopic circadian clocks. Cell. 2003 Jun 13; 113(6):755-66.
          View in: PubMed
        27. McDonald MJ, Rosbash M, Emery P. Wild-type circadian rhythmicity is dependent on closely spaced E boxes in the Drosophila timeless promoter. Mol Cell Biol. 2001 Feb; 21(4):1207-17.
          View in: PubMed
        28. Allada R, Emery P, Takahashi JS, Rosbash M. Stopping time: the genetics of fly and mouse circadian clocks. Annu Rev Neurosci. 2001; 24:1091-119.
          View in: PubMed
        29. Emery P, Stanewsky R, Helfrich-Förster C, Emery-Le M, Hall JC, Rosbash M. Drosophila CRY is a deep brain circadian photoreceptor. Neuron. 2000 May; 26(2):493-504.
          View in: PubMed
        30. Emery P, Stanewsky R, Hall JC, Rosbash M. A unique circadian-rhythm photoreceptor. Nature. 2000 Mar 30; 404(6777):456-7.
          View in: PubMed
        31. Emery P, So WV, Kaneko M, Hall JC, Rosbash M. CRY, a Drosophila clock and light-regulated cryptochrome, is a major contributor to circadian rhythm resetting and photosensitivity. Cell. 1998 Nov 25; 95(5):669-79.
          View in: PubMed
        32. Stanewsky R, Kaneko M, Emery P, Beretta B, Wager-Smith K, Kay SA, Rosbash M, Hall JC. The cryb mutation identifies cryptochrome as a circadian photoreceptor in Drosophila. Cell. 1998 Nov 25; 95(5):681-92.
          View in: PubMed
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