I. OVERALL Lead PI: Wendell Lim Exploring Design Principles of Cellular Control Circuits SUMMARY The UCSF Center for Systems and Synthetic Biology is focused on the fundamental question of how cells make decisions using genetically encoded molecular networks. Our philosophy is to use a combination of network engineering, analysis, and modeling to comprehensively understand the underlying algorithmic principles that cells use to make regulatory decisions. Our Center is therefore focused on developing new synthetic biology tools for network perturbation and rewiring, as well as quantitative, single-cell approaches for analyzing how such changes alter cellular behavior. Together such tools will allow us to better map genotype- phenotype relationships that control both dynamic and spatial responses in cells. For the second funding period, our Center is focusing much of its innovative effort on trying to apply our understanding of cell decision- making to medicine: our most forward-looking aim is to use synthetic biology approaches to engineer cells that could be used as therapeutics, including immune cells and stem cells with customized user-defined response behaviors. Designer therapeutic cells provide the ultimate testbed for our understanding of cellular logic. More broadly, the Center aims to play a leadership and catalytic role in the development of this transformative field, both at our own institution and within the national and international scientific and educational community.