Abstract:

For more than 50 years it was theorized that biological systems probabilistically generate variant phenotypes to preserve fitness in fluctuating environments—a process often referred to as ‘bet-hedging’ after the financial practice of diversifying assets to minimize risk in volatile markets. However, the molecular mechanisms enabling probabilistic bet-hedging had been unclear until about a decade ago when stochastic fluctuations (‘noise’) in transcription were found to drive HIV’s bet-hedging decision between active replication and latency (the chief barrier to curing HIV).  Noise was subsequently found to drive fate-selection decisions in bacteria, stem cells, and cancer. I will review HIV’s noise-regulating circuitry and discuss the discovery of a class of noise-modulating small molecules that can redirect cell-fate decisions across diverse biological systems.

Bio:

Weinberger is Professor of Biochemistry & Biophysics and Senior Investigator at the Gladstone Institutes, UCSF. He trained as a Lewis Thomas Fellow at Princeton, and received his Ph.D. in Biophysics at Berkeley as a Howard Hughes fellow. His lab pioneered the study of HIV’s decision circuit, providing the first experimental demonstration that stochastic fluctuations (‘noise’) in gene expression are harnessed for biological fate selection and discovered noise-enhancer molecules.  For these discoveries, Weinberger has been recognized by a number of awards, including: the Pew Scholarship in the Biomedical Sciences, the Alfred P. Sloan Fellowship, the Keck Research-Excellence Award, the Bill and Melinda Grand Challenges Award and is the only individual to receive the NIH Director’s Pioneer Award, Avant-Garde Award, and New Innovator Award. He is the founder of Autonomous Therapeutics Inc.

Date: June 22