Signaling and transcriptional control of metabolic pathways in Drosophila

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Biochemical pathways that metabolize nutrients such as sugars, fats and amino acids have been elucidated in classical studies. The influence of hormones in coordinating the activities of various organ systems in response to different dietary conditions has also been intensely investigated. By contrast, much less is known in multicellular organisms about the transcriptional and signaling mechanisms that regulate enzymes that actually carry out specific metabolic programs. This proposal uses Drosophila as a genetic model system to focus on two groups of transcriptional regulators that are involved in fat and amino acid breakdown. One is a zinc-finger transcription factor that is activated by dietary sugar and which transcriptionally represses genes encoding lipid and amino acid catabolizing enzymes. The other is a histone acetylase that regulates fat metabolism as part of a global starvation response. We will study how these transcription factors coordinate fat and amino acid breakdown, and how they are modulated by the conserved metabolic sensors AMP-activated protein kinase (AMPK) and Target of rapamycin (Tor). These studies are especially relevant in modern societies where diet driven metabolic disturbances have become a major health concern.