Dick McIntoshDistinguished Professor Emeritus
Porter room B027
Ph.D., Harvard University, 1968
Biophysical cytology; mechanisms of chromosome movement; 3-D reconstruction of cells, tissues, and organelles; molecular biology of cell division.
We study the mechanisms of mitotic chromosome movement using both structural and biophysical approaches: 1) We are using laser tweezers 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. Our 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. Our 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. 2) We are also studying the structure of the mitotic spindle by electron microscopy, using serial sections and tilts accompanied by computer-assisted reconstruction, to examine the 3-D architecture of microtubules and their attachments to both spindle poles and kinetochores. We are using EM immuno-cytochemistry to localize molecules significant for chromosome movement and EM tomography to characterize the details of kinetochore and centrosome association with spindle microtubules. 3) Our structural work includes the analysis of 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.