Validation of Novel Targets for Lifestyle Intervention using Animal Models

Analyze the metabolic effect of mutations in Rev-erb and RORα (in mice), and in other targets to be identified in WPs1 and 2 (in zebrafish) and determine whether environmental changes, such as exercise and scheduled food restriction or light, can improve the circadian control of metabolism in the absence of these factors.

Specific aims:

1. Characterize the metabolic phenotype of mice carrying mutations in Rev-erbα and RORα

2. Determine whether targeting the expression and/or activity of Rev-erbα and/or RORα with exercise and restricted feeding can revert circadian disorder-related metabolic abnormalities.

3. Validate a model of circadian disorders and sleep disturbances in zebrafish.

4. Study the effect of a knock-down of novel targets identified in WPs 1 and 2 in the model validated in aim3.