This interdisciplinary project will develop a principle of nonequilibrium physics called Maximum Caliber (MaxCal). MaxCal offers a general way to make dynamical models, particularly where fluctuations are important, as in single-molecule and few-particle systems. This project focuses on developing better kinetic models for applications in molecular and cellular biophysics. MaxCal will be applied to analyze a genetic toggle switch, a genetic timer, a three-gene repressilator circuit, and studies of a synthetic genetic oscillator with activation and repression, the B. Subtilis ComK gene regulatory feedback system. A way to identify hidden kinetic states from single molecule noisy data will be investigated as well. The PI will iterate with his experimental collaborators to test and advance MaxCal, motivate new experiments and develop insights into the principles governing these complex systems. Thus this project will facilitate the analysis of the rapidly growing body of experimental data, as well as circuit design by synthetic biologists.
The principles of MaxCal have broad utility: from nano-structures and nano-motor design to modeling neural systems, ecology, vehicular traffic, econophysics and interstellar chemistry. The project will impact multiple outreach efforts and new centers for collaboration/education. Graduate students and post docs in the Laufer Center and in the University of Denver's MCB program will be exposed to MaxCal and the stochastic physics in biology that are under development in this project. MaxCal applications from this proposal will be incorporated in the NESM chapter(s) of future editions of the textbook (used in 150 graduate and undergraduate courses worldwide) Molecular Driving Forces that the PI co-authors with Sarina Bromberg. Besides training post docs and graduate students in this project, at least one undergraduate student every year will be trained as part of their honors thesis, a requirement in the department of Physics and Astronomy at the University of Denver. The PI will also host high school students at Laufer Center to introduce them to university research, continuing the tradition he initiated at UCSF. The MaxCal project will also contribute to broader education by involving personnel from collaborators at the University of California, Berkeley; Arizona State University; and the University of Texas Southwestern Medical Center. The PI will make the computer codes freely available on the Laufer Center web server for broader usage.
This project is being supported jointly by the Physics of Living Systems Program in the Physics Division and by the Molecular Biophysics Program in Division of Molecular and Cellular Biosciences.
