Associate Investigator Molecular Biology, Mass General Research Institute

Associate Professor of Genetics Harvard Medical School

cytoskeleton; microtubules; single-molecule visualization; tirf microscopy; x-ray crystallography

For a living cell to function properly, its cellular processes must be strictly controlled not only in time but also in space. We are interested in how intracellular spatial organization on the micron-length scale is achieved by the collective activity of nanometer-sized proteins. We investigate this problem in the context of the microtubule cytoskeleton.

In eukaryotes, a wide range of cellular processes such as cell division, cell migration, axonal growth and assembly of flagella and cilia rely on the dynamic and precise organization of microtubules into specialized architectures. Increasingly sophisticated genomic and proteomic analyses have now provided us with a near-complete ‘parts-list’ of the proteins involved in assembling these microtubule-based structures. However, the molecular mechanisms underlying the proper formation and activity of even the minimal functional units of these structures still remain poorly understood. We aim to bridge this knowledge gap by ‘building’ or reconstituting microtubule-based architectures from the individual components.

We use a diverse set of experimental tools in our endeavor: integrating angstrom and nanometer-length scale information from X-ray crystallography and single-molecule visualization techniques with micron-length scale analysis of microtubule architectures using multi-color TIRF microscopy-based in vitro assays and cellular analyses of the cytoskeletal structures.