This project is to investigate the role of genes in aging, using Drosophila as a model system, in which the genes can be manipulated in various ways. One way is to screen for mutant genes that extend lifespan, as exemplified by the mutant methuselah, isolated in our laboratory. Since increased longevity is usually correlated with enhanced resistance to various forms of stress, screening for stress-resistant mutants is another approach to identifying life-assurance genes. A third approach is to identify genes whose expression is strongly increased in response to stress, then to determine whether overexpression of some such genes can extend lifespan. All these methods have provided candidate genes related to life extension. Chosen ones will be analyzed by molecular techniques to identify their tissue specificity of expression and their signal transduction and other cellular processes underlying aging, thus providing clues to roles in manipulation of specific gene expression that can contribute to enhanced, healthy lifespan.
| 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; Madrigal, Marisol et al. (2009) The Drosophila G protein-coupled receptor, Methuselah, exhibits a promiscuous response to peptides. Protein Sci 18:2203-8 |
| Heo, Jiyoung; Ja, William W; Benzer, Seymour et al. (2008) The predicted binding site and dynamics of peptide inhibitors to the Methuselah GPCR from Drosophila melanogaster. Biochemistry 47:12740-9 |
| Ja, William W; West Jr, Anthony P; Delker, Silvia L et al. (2007) Extension of Drosophila melanogaster life span with a GPCR peptide inhibitor. Nat Chem Biol 3:415-9 |
| 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 |
| Kapahi, Pankaj; Zid, Brian M; Harper, Tony et al. (2004) Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol 14:885-90 |
| Wang, Horng-Dar; Kazemi-Esfarjani, Parsa; Benzer, Seymour (2004) Multiple-stress analysis for isolation of Drosophila longevity genes. Proc Natl Acad Sci U S A 101:12610-5 |
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