- Society for Mathematical Biology
The Weinberger laboratory is developing strategies to manipulate pathogen lifecycles by obtaining a detailed understanding of their regulatory mechanisms. To this end, they are defining the fundamental molecular mechanisms and regulatory principles that underlie how viruses (and cells in general) "decide" between alternate fates such as replicative versus dormant states. The team couples quantitative single-cell imaging approaches with computational and mathematical models to define the architecture, kinetics, and function of regulatory circuits that modulate cell fate. A long-standing interest of the lab is to understand how HIV enters a long-lived dormant state termed proviral latency, which is a major barrier to eradicating the virus from infected individuals. Weinberger’s group has defined how molecular fluctuations (also known as stochastic "noise") in gene expression of HIV Tat, influence proviral latency. This molecular "noise" is an unavoidable aspect of life at the single-cell level and arises from random thermal fluctuations in the concentration of molecules (proteins, mRNAs, etc.) within the cell. They have shown that by manipulating the regulatory circuitry that controls HIV noise, they can alter the ability of HIV to enter proviral latency. Their ultimate goal is to develop novel therapies based on this newfound knowledge. One exciting example of this is their recent effort to engineer transmissible antivirals to treat HIV in resource-poor settings such as sub-Saharan Africa. Their models show that these transmissible therapies would be single-administration, could resist HIV mutation, could overcome behavioral barriers to disease control, and would automatically end up treating the highest-risk individuals.