Obesity is a complex disorder caused by an imbalance between food intake and energy expenditure. These processes normally are precisely regulated, so that body weight can remain constant over a long time, in spite of variable food intake and activity. This homeostasis suggests the presence of strong regulatory mechanisms, and most biological mechanisms have an underlying genetic basis. The isolation of the Drosophila adipose mutation in the 1960's demonstrated that Drosophila can become obese, since that mutation causes a doubling in the overall fat content of adult flies. The strength of Drosophila as an experimental organism lies not only in its amenability to large scale, fast, and cheap genetic screening, but also in many years of genetic analysis, climaxing with the complete sequence of its genome, which makes it relatively easy to identify and clone genes with interesting mutant phenotypes. The list of biological problems for which Drosophila has been used successfully as a model is impressive, including the identification of genes that regulate the circadian rhythm, aspects of behavior such as learning and memory, and nervous system development. Many of these genes have provided clues to the discovery of their mammalian homologs. The use of Drosophila in obesity research opens the prospect of large-scale genetic screens to identify genes responsible for appetite control, body weight regulation, and fat storage, as well as analysis of the underlying biological mechanisms. We have isolated a series of obese mutants of Drosophila.
The specific aims of the project will be to characterize their phenotypes, clone the genes, analyze the affected biochemical pathways, and isolate suppressor genes to reverse the genetic obesity defects.
|Cho, Jaehyoung; Hur, Jae H; Graniel, Jacqueline et al. (2012) Expression of yeast NDI1 rescues a Drosophila complex I assembly defect. PLoS One 7:e50644|
|Al-Anzi, Bader; Armand, Elena; Nagamei, Paul et al. (2010) The leucokinin pathway and its neurons regulate meal size in Drosophila. Curr Biol 20:969-78|
|Al-Anzi, Bader; Sapin, Viveca; Waters, Christopher et al. (2009) Obesity-blocking neurons in Drosophila. Neuron 63:329-41|
|Carvalho, Gil B; Ja, William W; Benzer, Seymour (2009) Non-lethal PCR genotyping of single Drosophila. Biotechniques 46:312-4|
|Ja, William W; Carvalho, Gil B; Zid, Brian M et al. (2009) Water- and nutrient-dependent effects of dietary restriction on Drosophila lifespan. Proc Natl Acad Sci U S A 106:18633-7|
|Ja, William W; Carvalho, Gil B; Mak, Elizabeth M et al. (2007) Prandiology of Drosophila and the CAFE assay. Proc Natl Acad Sci U S A 104:8253-6|
|Carvalho, Gil B; Kapahi, Pankaj; Anderson, David J et al. (2006) Allocrine modulation of feeding behavior by the Sex Peptide of Drosophila. Curr Biol 16:692-6|
|Carvalho, Gil B; Kapahi, Pankaj; Benzer, Seymour (2005) Compensatory ingestion upon dietary restriction in Drosophila melanogaster. Nat Methods 2:813-5|