University of Southern California
Ray R. Irani Hall
Molecular and Computational Biology
Molecular Biology Seminar
Leor Weinberger
UC San Diego
“Exploiting Gene – Expression
Circuitry & Noise for Therapy”
Abstract:
Viral dormancy (i.e. latency) remains the most problematic obstacle facing treatment and eradication of viral pathogens, in particular HIV-1. The mechanisms underlying how animal viruses establish, maintain, and exit latency remain largely unknown. Based on findings that stochastic noise in gene expression (the random fluctuations of biochemical molecules) within a single cell can drive cell-fate decisions in phage and bacteria, we pioneered a system to study HIV-1 gene expression noise at the single-cell level. Our previous work established that HIV-1 utilizes a probabilistic molecular “switch” between proviral-latency and active-infection by encoding transcriptional positive feedback to amplify gene-expression noise (Weinberger et al Cell, 2005; PLoS Biology 2007). Using a novel ‘noise-imaging’ technique that exploits stochastic noise as a measurement probe, we mapped the HIV-1 feedback circuit and succeeded in manipulating HIV-1 feedback, and noise, to bias infected cells towards maintaining latency and not reactivating (Weinberger et al. Nature Genetics, 2008). This noise-imaging technique has now been applied to map the regulatory circuit of the human herpesvirus cytomegalovirus (CMV) in single cells (Wong et al. submitted, 2009). A quantitative understanding of the regulatory ‘switches’ controlling viral replication may lead to innovative therapies to purge or perturb the viral dormancy.
Friday, September 11, 2009
12:00 noon
RRI 101
