New Scholar Award in Aging
Antonio Bedalov, M.D., Ph.D.
Fred Hutchinson Cancer Research Center

Chemical Genetic Approaches to Aging

Chemical genetics relies on using small, cell-permeable molecules that interact with proteins and create a loss or a gain of function of proteins similarly to genetic mutations. The active compounds are obtained by the in vivo screening of libraries of chemicals for the desired cellular phenotype, similarly to finding mutants in traditional genetic screens. Using a cell based screen in yeast we have recently identified a small molecule inhibitor of Sir2p, the NAD dependent histone deacetyalse implicated in regulation of life span in yeast and nematodes. By exploiting the ability to conditionally inactivate Sir2 activity with the drug, we will dissect the pathways that are important for promoting longevity by Sir2 in higher eukaryotes.

The finding that single gene mutations can increase life span in model organisms suggests that interfering with functions of specific proteins may slow down the aging process. Since mutations that promote longevity are associated with increased resistance to stress, we will perform cell-based screens in model organisms for compounds that promote viability in unfavorable growth conditions.

Contact Dr. Bedalov.