Molecular analysis of genes controlling food intake and growth in Drosophila

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The proposal addresses the question how food intake and growth are coordinated in a multicellular organism. Using Drosophila as a genetically accessible system, we are interested in identifying the molecular signals that control food intake, which organs they orginate from and act on, and how their activities are regulated in response to differing growth conditions. In a genetic screen for mutants that are defective in feeding, we have identified three genes that are required for proper food intake and growth of the larva. The first gene we have molecularly characterized is pumpless, which encodes an enzyme involved in glycine catabolism and which is expressed exclusively in the fat body. We have proposed a model in which amino acid dependent signal(s) arising from the fat body induces cessation of feeding in the larva; this signaling system may also mediate growth transition from larval to the pupal stage during Drosophila development. The goal of the proposed projects is to investigate this model and to molecularly characterize the other two genes that have been identified. The molecular cloning of these genes, combined with a detailed biochemical and genetic analysis of the gene products, would be a first step in providing mechanistic insights into how an organism coordinates growth pattern with food intake behavior.