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).

F32GM074277

2004-09-01

2006-08-31