CAREER:Research and Education in Theoretical Biophysics: Physical Principles Governing Biochemical Signaling Networks

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The research objective of this CAREER award aims at understanding the principles governing the design of biochemical signaling networks. The cell's crucial functions, growth, differentiation and the generation of specialized properties, are carried out by networks of biochemical reactions. The research will examine the theoretical limits set by fundamental physics, such as thermal fluctuations leading to chemical kinetic rate fluctuations and diffusive noise, on the accuracy of biochemical signaling. The idea of performance at the limits set by physical laws will be explored to understand biochemical signaling processing by the cell, from the level of a single network element, such as a biochemical switch, to the organization of the signaling network governing precise morphogen gradient detection in early embryonic development. Design principles ensuring robustness to inherent sources of noise will be investigated for various biochemical signaling networks, such as the bacterial chemotaxis signal transduction network and phototransduction in vertebrate retinal cells. Optimality in biochemical signal processing will be explored in the context of the well-characterized bacterial signal transduction network from information theoretic considerations. Organizing principles such as performance at physical limits will be used to constrain unknown and partially known molecular mechanisms. Synergistic activities that fall under the long-term scope of this CAREER activity involve ongoing collaborations with biologists on problems inspired directly by experiments. These include understanding optimal strategies in nutrient uptake by Caulobacter crescentus and the role of motility and chemotaxis in initial stages of biofilm formation. The educational component builds on the interdisciplinary nature of the research platform and provides seed initiatives for further developing the nascent graduate biophysics program in the Physics department at Indiana University, Bloomington, and interfacing it with the undergraduate curriculum. It encompasses the development of courses at three levels, for non-scientists, undergraduate science majors as well as advanced graduate students. The education and outreach efforts are strongly aimed at the notion that scientists and non-scientists alike are confronted by issues and problems that require multidisciplinary training and thinking.Funding for this award is provided by the Division of Physics in the Directorate for Mathematical and Physical Sciences and by the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences.