Coordination of metabolic and signal transduction pathways

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During development cells divide, differentiate, and organize themselves into specialized tissues and organs. These processes require cellular building blocks that are produced by metabolic pathways using precursors supplied in the diet. When nutrients are lacking, or when there is metabolic dysfunction, cells must adapt to optimize the use of nutrients, prioritize certain cellular functions and adjust others to cope with the availability of critical metabolites. For these reasons, cells must convey metabolic information to the cellular signaling pathways that regulate growth and development. The mechanisms involved in conveying this information are not completely understood. ***Our research program seeks to understand how metabolic insufficiencies and imbalances are communicated to the systems that regulate growth and development in a complex, multi-cellular organism. We are using the nematode worm C. elegans for these analyses because it has invariant developmental program; animals always have the same number of cells, their developmental timing is highly reproducible and developmental stages can easily be identified. These animals serve as a practical system to study and identify developmental effects resulting from the perturbation of metabolic or signaling proteins. ***Our proposed program will: 1) identify metabolic imbalances that influence development 2) identify and characterize cellular signaling pathways that sense and respond to these metabolic imbalances 3) determine how metabolic dysfunction in one tissue affects other tissues. These analyses will improve our understanding of the basic biological mechanisms through which metabolic dysfunction mediates effects on development. Metabolic pathways from C. elegans to humans are highly conserved and therefore molecular events that we uncover in C. elegans are likely to occur in other organisms. **