Design principles of biological circuits

We study how the structure of naturally occurring biological circuits - the precise way that their components are wired together - provides them with special dynamical features. One such feature is robustness [Alon 1999]: ensuring that the essential function of the circuit is carried out precisely despite natural cell-cell variation in the concentrations of the proteins that make up the circuit.

We study how robustness can arise from  paradoxcial components, that have at the same time,  two opposing effects on the same target or biological process [Shinar 2007]. Examples include bifunctional enzymes in the control on nitrogen regulation [Hart 2009 , Hart 2013] and key metabolic steps in bacteria and plants. 

We also study design principels of circuits made of interacting cells [Hart 2012]. Here, paradoxical signaling molecules, such as immune cytokines that instruct cells to both proliferate and die, can provide ropbust input-output relationships to cell circuits.

Other dynamical features we study include fold change detection [Goentoro 2009, Shoval 2010,Hart 2013]: circuits that allow cells to respond to relative changes in input signal, rather than absolute changes.