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Connect biochemical measurements, the development of novel biophysical assays, and mathematical modeling to build a comprehensive understanding of the function of bimolecular circuits
Ph.D., Harvard University, 2006.
Dept. of Molecular Genetics and Cell Biology, Dept. of Physics, Inst. for Genomics and Systems Biology, and the College.
Helen Hay Whitney Foundation Fellow, 2008
Burroughs-Wellcome Career Award, 2009
Living cells are capable of remarkably sophisticated behavior, combining information from the external environment with an internally stored model of past events to make decisions about how to respond to challenges. These decisions can be thought of as information processing tasks that must occur robustly in the face of various potentially disruptive fluctuations in the conditions inside the cell. Fundamentally, these computations are carried about by networks of proteins and nucleic acids, specialized macromolecular machines sculpted by evolution to channel specific chemical reactions.
We are interested in uncovering the design principles of these networks that allow them to function reliably. We are currently interested in the circadian rhythm, a nonlinear oscillator in living cells that is normally phase locked to the daily rhythms in the external environment and that coordinates cyclic behavior and metabolism in living organisms. We are exploiting a particularly powerful model system from cyanobacteria, where the core oscillator can be studed in a test tube using a mixture of three purified proteins (KaiA, KaiB, and KaiC). Our approach combines methodology from various disciplines including dynamical systems theory, engineering, biochemistry, and quantitative microscopy.
Lakdamyali M., Rust, M.J., Babcock, H. P., Zhuang, X. (2003). Visualizing infection of individual influenza viruses. Proceedings of the National Academy of Sciences of the United States of America, 100, 9280-9285. PMCID: PMC170909
Rust, M.J., Lakadamyali, M., Zhang, F., Zhuang, X. (2004). Assembly of endocytic machinery around individual influenza viruses. Nature Structural and Molecular Biology, 11, 567-573. PMCID: PMC2748740
Lakadamyali, M., Rust, M.J., Zhuang, X. (2006). Ligands for clathrin-mediated endocytosis are differentially sorted into distinct populations of early endosomes. Cell, 124, 997-1009. PMCID: PMC2660893
Rust, M.J., Bates, M., Zhuang, X. (2006). Sub-diffraction limit imaging by stochastic optical reconstruction microscopy (STORM). Nature Methods, 3, 793-796. PMCID: 16896339
Rust, M.J., Markson, J., Lane, W. S., Fisher, D., O’Shea, E. K. (2007). Ordered phosphorylation governs oscillation of a three-protein circadian clock. Science, 318, 809-812. PMCID: 2427396
van der Schaar, H. M., Rust, M.J., Chen, C., van der Ende-Merselaar, H., Wilschut, J., Zhuang, X. (2008). Dissecting the cell entry of dengue virus by single-particle tracking in live cells. PLoS Pathogens, 4(12), e1000244. PMCID: PMC2592694
Rust, M.J., Golden, S., O’Shea, E. K. (2011). Light-driven changes in energy metabolism directly entrain the cyanobacterial circadian oscillator. Science, 331, 220-223. PMCID: PMC3309039
Phong, C., Markson, J., Wilhoite, C., Rust, M.J. (2013). Robust and tunable circadian rhythms from differentially sensitive catalytic domains. Proceedings of the National Academy of Sciences of the United States of America, 110, 1124-1129. PMCID: PMC3549141