Identifying and characterizing physiologic mechanisms that regulate organ communication and function during development and adulthood is vital for understanding how many important human health problems arise and intensify during our lifetimes. This proposal outlines a research strategy to further characterize key signaling systems that regulate critical and likely conserved physiological processes. These include determining how Drosophila TGF-? -type factors control fundamental aspects of muscle, and fat body cellular function and how neuroendocrine mechanisms regulate steroid production, release, and trafficking in response to nutrient availability. We will use a wide variety of modern biological investigative methods including genetic analysis, metabolomics, transcriptome characterization, chromatin immunoprecipitation experiments, biochemistry, and optical/EM imaging to answer these questions. Impact on human health: The successful completion of these aims will provide novel insight into how TGF-?-type factors parse out specific, as well as combinatorial control, over fundamental cellular processes and inter-organ communication programs. It is expected that this knowledge will serve as useful paradigm for understanding the more complex vertebrate system and will afford novel insights into mechanisms that contribute to a number of complex human disorders including obesity, metabolic syndrome, and muscle wasting. In addition, our identification and characterization of new signals that regulate steroid production and trafficking in response to various environmental cues, should provide fresh insights into ways in which nutrition gates puberty in humans.
The studies described in this proposal will expand our knowledge of inter-organ communication systems that are essential to maintain physiological homeostasis during an organism's development and interactions with its surroundings. Identifying and characterizing these mechanisms is central to understanding many fundamental issues that underlie significant human health problems including obesity, cancer, and aging.
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