Office: Porter Biosciences B027
Lab: Porter Biosciences B019
I study the mechanisms of mitotic chromosome movement using both structural and biophysical approaches. Laser tweezers are used to measure the mechanical properties of the interactions between microtubules and the several molecules and structures that are important for chromosome motion at mitosis: static linkers like microtubule associated proteins, potentially dynamic linkers like the DAM/DASH complex, and fully dynamic linkers like motor enzymes. The goal is to understand the interplay between the enzymatic activity of such linkers, if any, and the polymerization dynamics of tubulin as microtubules lengthen and shorten. The special focus in this work is on proteins and ultimately the chromosomes from the fission yeast, Schizosaccharomyces pombe, whose mitotic processes are now quite well understood and whose chromosomes are amenable to such biophysical analysis.
Electon microscopy is employed to study the structure of the mitotic spindle. Serial sections and tilts are accompanied by computer-assisted reconstruction to examine the 3-D architecture of microtubules and their attachments to both spindle poles and kinetochores. EM immuno-cytochemistry is used to localize molecules significant for chromosome movement and EM tomography to characterize the details of kinetochore and centrosome association with spindle microtubules. I also analyze other microtubule-dependent devices, such as the eukaryotic flagellum and endocytosis. The former is under investigation by cryoelectron tomography, the latter through more conventional electron tomography but with an effort to develop tools to use as markers for the localization of specific membrane components.