Overview

Our work focuses on understanding the principles underlying cell-fate decisions and, in turn, utilizing these to rationally target fate-regulating circuits for therapeutic benefit.

To achieve this we couple mathematical methods with ‘wet-lab’ experiments to identify fundamental regulatory principles governing fate selection in viruses and developmental systems. 

Viruses as model systems

Viral pathogens are attractive models for fate selection because pathogenicity generates inherent fitness trade-offs (e.g. pathogens must balance transmission against virulence). 

To overcome these inherent trade-offs, one strategy viral pathogens have evolved is ‘bet-hedging’ between active and latent states, reviewed in (Weinberger and Weinberger, 2013).  Since viruses are genetically constrained—selecting for minimalist regulatory circuits—they are ideal for identifying core regulatory principles underlying biological bet-hedging decisions. 

Our historic work focused on exploring the fundamental fate selection circuitry of two viruses: HIV and the human herpesvirus 5 or cytomegalovirus (CMV).  The following pages (linked left) expand more deeply on our current projects.