Inferring the Physics of Living Systems from Dynamic Light Microscopy Data

Massachusetts Institute Of Technology, Cambridge MA

Investigators

Abstract

In this project the PI will investigate the role of contractile actin networks in driving shape changes and morphogenesis in Drosophila embryos. Contractile actin networks are increasingly being shown to play a central role in fundamental biological processes involving cellular transport including cell division and embryogenesis. A physics-based approach that integrates quantitative analysis of fluorescence microscopy data with mechanistic, physics based modeling is proposed to investigate these processes. A major challenge posed by this data-driven modeling approach is the unbiased evaluation of competing physical models. To meet this challenge, a Bayesian inference framework is explored that models noise in the data generation process to systematically test competing hypotheses of transport mechanisms. Specific contributions of this research project include a unified, physical understanding of how dynamic, contractile actin meshworks operate to transport organelles and entire cells during basic biological processes including cell division and embryogenesis. Further, a data-driven approach to bridging physics-based transport models with fluorescence microscopy data sets is explored that will be of broad utility to the biological physics community. Contractile actin networks are protein networks present in eukaryotic cells that play an important role in cell division, cell movement, and tissue development. However, a mechanistic, physical understanding of how short time-scale, dynamic contractions of actin at the subcellular scale interact mechanically to coordinate cellular transport at larger length and time-scales does not exist. Resolving this mechanism requires a quantitative, physics-based approach that models contraction-driven transport at multiple scales ranging from single cells to collections thereof. The present project is at the forefront of this research area, which is of great importance to our scientific understanding the roles of contractile actin networks in development. Educational initiatives being advanced by the PI include undergraduate and graduate curriculum enhancement, including the new graduate elective offered in the Department of Biological Engineering, Physical Biology, and a new Institute-wide seminar series in Biophysics at MIT. As a result of the present research project, the PI is establishing a webserver for objective, Bayesian analysis of transport measurements to infer physical transport models in a variety of scientific disciplines, updating a webserver for integration of physics-based modeling into molecular animations of proteins, protein assemblies, and cytoskeletal dynamics for educational purposes, and developing a virtual laboratory in molecular and cellular biophysics for students at City on a Hill, a local charter high school serving under-represented minorities in the Boston area. Educational and research activities of the PI will be further disseminated via continuous rotation of undergraduate students from the Biological Engineering Research Experience for Undergraduates program and MIT's Undergraduate Research Opportunities Program, as well as from developing foreign countries.