Abstract

The long-term goal of this proposal is to identify the components and mechanisms involved in regulating circadian patterns of clock gene expression in mammals. Mammalian circadian clock proteins are found in huge complexes, that differ in composition at various times of day. A proteomics based approach will be used to identify unknown proteins bound in these complexes, in an in vitro cellular context. Identified proteins will be evaluated for in vivo interactions to confirm the identified interactions are biologically relevant. The functions and necessity of the biologically interacting proteins within the mammalian circadian clock will then be determined. Thus, this work will identify novel circadian clock proteins, which may serve as therapeutic targets for ameliorating clock related ailments (e.g. jet lag, shift work) and more serious conditions such as circadian rhythm sleep disorders and other clock-related psychological disorders (e.g. seasonal affective disorder). ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM074277-02
Application #
6945738
Study Section
Special Emphasis Panel (ZRG1-F02A (20))
Program Officer
Portnoy, Matthew
Project Start
2004-09-01
Project End
2006-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
2
Fiscal Year
2005
Total Cost
$49,928
Indirect Cost

  Institution

Name
University of Massachusetts Medical School Worcester
Department
Biology
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655

  Publications

DeBruyne, Jason P; Weaver, David R; Dallmann, Robert (2014) The hepatic circadian clock modulates xenobiotic metabolism in mice. J Biol Rhythms 29:277-87
Dallmann, Robert; DeBruyne, Jason P; Weaver, David R (2011) Photic resetting and entrainment in CLOCK-deficient mice. J Biol Rhythms 26:390-401
Etchegaray, Jean-Pierre; Machida, Kazuhiko K; Noton, Elizabeth et al. (2009) Casein kinase 1 delta regulates the pace of the mammalian circadian clock. Mol Cell Biol 29:3853-66
Debruyne, Jason P (2008) Oscillating perceptions: the ups and downs of the CLOCK protein in the mouse circadian system. J Genet 87:437-46
DeBruyne, Jason P; Weaver, David R; Reppert, Steven M (2007) CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock. Nat Neurosci 10:543-5
Debruyne, Jason P; Noton, Elizabeth; Lambert, Christopher M et al. (2006) A clock shock: mouse CLOCK is not required for circadian oscillator function. Neuron 50:465-77
Etchegaray, Jean-Pierre; Yang, Xiaoming; DeBruyne, Jason P et al. (2006) The polycomb group protein EZH2 is required for mammalian circadian clock function. J Biol Chem 281:21209-15