Identifying Novel Drug Targets for the Treatment of Tuberous Sclerosis Complex Using High Throughput Technologies
Abstract
In a patient with Tuberous Sclerosis Complex (TSC), the problematic cells that initiate and constitute tumors have lost TSC1 or TSC2 function. A promising approach for treatment would be to target members of the pathway with which TSC1/2 proteins interact. In cultured drosophila cells, we proposed to rapidly identify genes whose RNAi-mediated reduction in expression (1) Prevents growth/proliferation of TSC1 or TSC2-deficient cells without affecting normal cells. (2) Induces apoptosis/cell death in TSC1 or TSC2-deficient cells without killing normal cells. (3) Reverts TSC1 or TSC2-deficient cells to a normal phenotype, as determined by measuring a reporter of cell growth pathway activation and cell morphology. We have (1) advanced genome-wide RNA interference living cell microarrays from proof-of-principle to a robust technology. (2) developed software to analyze these screens, a previously formidable challenge, and (3) completed genome-wide experiments on the scale required to complete the goals of this proposal. We will repeat these experiments under several experimental conditions in order to identify genes involved in the TSC pathway.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2006
- Accession Number
- ADA460471
Entities
People
- David M. Sabatini
Organizations
- Whitehead Institute