Grant: Discovery Grants Program - Individual

I propose to develop a set of tools for systems biology based on techniques deriving from theoretical chemistry. Metabolic control analysis (MCA) is a successful theory for analyzing the response of a biochemical system to small changes in (e.g.) concentrations of key proteins. The current theory is based on equations which are only strictly valid when large numbers of molecules are involved. This is not the case for many important processes in living cells. I propose to develop a version of MCA which is valid in systems with few copies of some molecules. This will be useful to understand genetic regulation since genes are only present in two copies in our cells. I also propose to work on methods for reducing (simplifying) models involving small numbers of molecules. This is important because these models, paradoxically, are very complex and can overwhelm even the largest computers. Finally, I am pursuing applications which will allow me to showcase our theoretical methods in the areas of cellular biology and of developmental biology. Projects include the modeling of transport of RNA out of the nucleus, of development of veins in plant leaves, and of the maintenance of left-right asymmetry during vertebrate embryogenesis.