Transient-mediated decision-making in HIV-1 (or why bistability is unnecessary)

21 March 2008

Leor Weinberger
Department of Chemistry and Biochemistry
UC San Diego

Abstract

Equilibrium (steady-state) behavior and bistability are often assumed to be necessary features of genetic "on/off" switches. However, when one behavior of the switch is transient or destroys the cell the underlying genetic circuit need not be bistable. Instead, transient excursions may allow multiple behaviors with switching arbitrated by the lifetime of the transient signal.

Using HIV-1 as a model system, I will discuss our data and models on how a viral fate decision is arbitrated by transient gene expression in a deterministically monostable circuit. Specifically, I will discuss: (i) experimental evidence that the HIV Tat circuit lacks bistability, (ii) a counter-model based on transient signal lifetime: "Feedback Dissipation", and (iii) how to exploit the inherent stochastic noise in gene expression to measure the non-equilibrium transient decision in HIV.

current theory lunch schedule