Project Abstract Biological networks organize specific chemical reactions in space and time. In cell signaling, scaffold proteins coordinate the formation of physical complexes that link multiple signaling proteins together. These scaffold proteins have many functional roles: they can recruit proteins to particular subcellular locations, serve as platforms to recruit regulatory factors, and direct pathways to specific outputs. Scaffold proteins are also thought to accelerate specific biochemical reactions when enzymes and proteins are brought together to the same spatial location. Similar spatial organizing principles are involved in genome regulation, where the 3D structure of the genome appears to play a regulatory function by positioning genes in proximity to remote DNA regulatory sites or to localized proteins. Again, physical proximity is thought to promote specific biochemical processes in gene regulation. While there is extensive evidence that spatial organization is important for biological function, we lack a quantitative framework to understand how enzyme activities and other biochemical functions are affected by spatial organization. This gap in our knowledge must be addressed to understand fundamental processes like cell signaling and gene regulation, and to intervene therapeutically when these processes are misregulated. To address this challenge, I propose to develop new tools to systematically perturb structural organization both in cell signaling networks and in the genome. I plan to use these tools to understand the underlying mechanistic principles that enable cells to control biochemical reactions with incredible spatial and temporal precision.