Image correlation studies of distributions and dynamics of macromolecules in cells

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One of the major scientific challenges in the era of emergent quantitative biology and molecular medicine will be to develop a physico-chemical understanding of how biological macromolecules interact within living cells so as to control biochemical processes. Currently, there are only a limited number of methods that allow scientists to peer directly into a living cell and monitor the complex behavior and interactions of the macromolecules in real time. The focus of my research is novel fluctuation microscopy techniques applied to the measurement of the properties of macromolecules within living cells. I am interested in pushing the limits of image based fluorescence fluctuation methods using high time resolution array detector cameras. I am also interested in understanding how cells regulate their signaling, adhesion and migration at the molecular level. Cell adhesion plays an important role in the formation of tissues during development and wound healing. It is also a pivotal process in certain disease states such as metastasis of cancer cells. I will combine fluorescence microscopy (confocal and two-photon fluorescence microscopy) with our recently developed spatio-temporal image correlation spectroscopy (STICS) and spatial intensity distribution analysis (SpIDA) methods and traction force microscopy (TFM) to simultaneously map forces, dynamics and clustering of adhesion proteins responsible for generating the forces in living cells. Such in situ measurements will be essential for unraveling the complex molecular mechanisms that govern mechanostranduction in cells.