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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

Post Docs

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

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.

One or more keywords matched the following items that are connected to Emery, Patrick
Item TypeName
Academic Article The cryb mutation identifies cryptochrome as a circadian photoreceptor in Drosophila.
Academic Article CRY, a Drosophila clock and light-regulated cryptochrome, is a major contributor to circadian rhythm resetting and photosensitivity.
Academic Article A unique circadian-rhythm photoreceptor.
Academic Article Drosophila CRY is a deep brain circadian photoreceptor.
Academic Article Wild-type circadian rhythmicity is dependent on closely spaced E boxes in the Drosophila timeless promoter.
Academic Article A subset of dorsal neurons modulates circadian behavior and light responses in Drosophila.
Academic Article Interactions between circadian neurons control temperature synchronization of Drosophila behavior.
Academic Article Cryptochromes define a novel circadian clock mechanism in monarch butterflies that may underlie sun compass navigation.
Academic Article Stopping time: the genetics of fly and mouse circadian clocks.
Academic Article A constant light-genetic screen identifies KISMET as a regulator of circadian photoresponses.
Academic Article Light and temperature control the contribution of specific DN1 neurons to Drosophila circadian behavior.
Academic Article The circadian clock gates the intestinal stem cell regenerative state.
Academic Article A role for Drosophila ATX2 in activation of PER translation and circadian behavior.
Academic Article Drosophila clock can generate ectopic circadian clocks.
Academic Article Roles of the two Drosophila CRYPTOCHROME structural domains in circadian photoreception.
Academic Article Ectopic CRYPTOCHROME renders TIM light sensitive in the Drosophila ovary.
Academic Article Glia got rhythm.
Academic Article Circadian rhythms: timing the sense of smell.
Academic Article Circadian rhythm of temperature preference and its neural control in Drosophila.
Academic Article Circadian rhythms: An electric jolt to the clock.
Academic Article KAYAK-? modulates circadian transcriptional feedback loops in Drosophila pacemaker neurons.
Academic Article GW182 controls Drosophila circadian behavior and PDF-receptor signaling.
Concept Drosophila melanogaster
Concept Drosophila
Concept Drosophila Proteins
Academic Article Morning and evening oscillators cooperate to reset circadian behavior in response to light input.
Academic Article Studying circadian rhythms in Drosophila melanogaster.
Academic Article Mutagenesis with Drosophila.
Academic Article RNA extraction from Drosophila heads.
Academic Article Protein extraction from Drosophila heads.
Academic Article Connecting Circadian Genes to Neurodegenerative Pathways in Fruit Flies.
Academic Article The molecular ticks of the Drosophila circadian clock.
Academic Article miR-124 Regulates the Phase of Drosophila Circadian Locomotor Behavior.
Academic Article SIK3-HDAC4 signaling regulates Drosophila circadian male sex drive rhythm via modulating the DN1 clock neurons.
Academic Article Neural Network Interactions Modulate CRY-Dependent Photoresponses in Drosophila.
Academic Article Reconfiguration of a Multi-oscillator Network by Light in the Drosophila Circadian Clock.
Academic Article Drosophila Cryptochrome: Variations in Blue.
Academic Article Drosophila PSI controls circadian period and the phase of circadian behavior under temperature cycle via tim splicing.
Academic Article Dopaminergic Ric GTPase activity impacts amphetamine sensitivity and sleep quality in a dopamine transporter-dependent manner in Drosophila melanogaster.
Academic Article Astrocytic GABA transporter controls sleep by modulating GABAergic signaling in Drosophila circadian neurons.
Academic Article PERIOD Phosphoclusters Control Temperature Compensation of the Drosophila Circadian Clock.
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  • Drosophila