Project 3: Small molecules as chemical tools to manipulate circadian clocks in mammals

Dr. Steven McKnight and Dr. Joseph Takahashi, Project Leaders

Using a cell-based circadian assay system from a robustly rhythmic cell line derived from mPer2::luciferase knockin mice, we will conduct high-throughput screens of a 200,000 compound library at UT Southwestern to find changes in period and amplitude of circadian rhythms. These chemical hits will be confirmed using tissue explants of the SCN and peripheral tissues using mPer2::luc knockin mice. In addition, initial library hits will be followed up using medicinal chemistry approaches. Dr. McKnight’s Biochemistry Department has built a high-throughput screening system (HTS) at UT Southwestern Medical Center. The HTS is supported by a chemistry core laboratory for resynthesis, as well as five faculty who are synthetic organic chemists capable of providing critical advice in the advancement of the most promising compounds.