Fluctuation Theories for Complex Biological Systems

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Intellectual Merit: This project addresses the roles of random fluctuations in biology, how they arise and spread, and how they can be controlled and exploited. Life at all levels of complexity is a battle between randomizing and correcting statistical tendencies. Births and deaths of individual cells or organisms create spontaneous fluctuations in population sizes that can spread through interaction networks and potentially randomize other parts of the system. The project will focus on the derivation of theorems that hold for large families of processes, to rigorously understand the broader design principles of biological systems, rather than constructing detailed models for specific systems. The theory will be applied to molecular systems to elucidate, for example, how genes are reliably expressed to produce protein and RNA molecules, as well as to populations of cells and organisms to account for the natural fluctuations in population sizes. The project is technically and experimentally innovative in that results from traditionally separate areas of applied mathematics will be synthesized to provide a framework for isolating and testing individual assumptions regarding the behavior of experimental systems. It is anticipated that the results of the project will be broadly applicable to quantitative analysis of arbitrarily complex biological systems. Broader Impacts: The proposed extensions of fundamental theory for fluctuating complex systems will provide a better understanding for how biological systems ranging in size from molecular networks in individual cells to populations of organisms can be driven to extinction through fluctuations in population sizes. To ensure that the results and methods have maximal impact on the broader scientific community, appropriate courses will be developed for advanced undergraduate and graduate levels, that are designed to be accessible to students from all areas of natural science. In addition, conferences will be organized to bring together scientists from very different disciplines, primarily from molecular biology and ecology. Finally, the PI will provide lectures at a lay level for the family program of the Harvard Museum of Natural History, demonstrating to the general public how the same dynamic principles appear at all levels of biological complexity from molecules to viruses, cells or even large organisms.