DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Identifying Novel Drug Targets for the Treatment of Tuberous Sclerosis Complex Using High Throughput Technologies

Principal Investigator: SABATINI, DAVID M
Institution Receiving Award: WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH
Program: TSCRP
Proposal Number: TS043017
Award Number: W81XWH-05-1-0138
Funding Mechanism: Concept Award
Partnering Awards:
Award Amount: $100,000.00


PUBLIC ABSTRACT

In a patient with Tuberous Sclerosis Complex, the problematic cells that initiate and constitute tumors have lost TSC1 or TSC2 function. TSC1 and TSC2 are proteins involved in a pathway controlling cell growth, the process through which cells accumulate mass. A cell makes the decision to accumulate mass based on its environment, including growth factors, nutrients, and stress. The outcome of this decision affects the size of the cell and its rate of proliferation. Unfortunately, very little is known about the proteins in these pathways or how they interact, so we cannot make an educated guess about which proteins should be targeted to kill, arrest, or revert TSC mutant cells. Even for those proteins that are already known to be in the pathway, predicting the effects on living cells of targeting those proteins is unreliable. Using Drosophila as a model system, this study aims to test every gene in the genome systematically using high throughput imaging. The goal will be to identify genes that, when their expression is decreased by RNA interference, cause only cells deficient in TSC1 or TSC2 function to arrest, die, or revert to normal without affecting normal cells. These genes would be excellent candidates for future drug development.