Interplay between signaling and noise in cellular decision making

? DESCRIPTION (provided by applicant): The classical view of cellular decision making is that individual cells make predictable choices based on the information presented to them in the form of both environmental and intracellular signals. However, recent theoretical and experimental studies have unambiguously shown that biological noise, typically arising from inherent stochasticity in underlying biochemical reactions or variability in cellular machinery, ca often play a crucial role in influencing cell fate outcomes. In this proposal, we examine the interconnected roles of signaling and noise in cell differentiation and we hypothesize that noise in cell signaling molecules can engender entirely new trajectories from one cell state to another. We will use computational and synthetic biology approaches to understand how such trajectories may arise, and we will use systems biology approaches to experimentally demonstrate and manipulate these trajectories in model systems of neurogenesis and hematopoiesis. The results of our study will yield deeper insights into the fundamental mechanisms underlying cellular decision making, particularly in differentiation, and should allow for more robust engineering of stem and progenitor cells for applications in regenerative medicine.