Time lapse of wild type centromere (green) and Sad1 (red)
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Macromolecular complexes embedded in the nuclear envelope physically couple the cytoskeleton to the nucleus. These molecular bridges (LINC complexes) allow the cytoskeleton to regulate nuclear position within the cell. In addition, they provide a mechanism for signals to be mechanically transduced between the cytoplasm and nucleus. More broadly, nuclear envelope membrane proteins serve to compartmentalize chromatin within the nucleus.
Our lab uses two primary experimental systems: the fission yeast, Schizosaccharomyces pombe, and tissue culture cell/mouse models.
Our team focuses on the functions of proteins embedded in the nuclear envelope as well as general chromatin organization and dynamics and the functions of nuclear subcompartments.
At the nuclear envelope, we are investigating how force transduction from adhesions and the cytoskeleton to the nuclear lamina through the LINC complex influences gene regulation (see Current Research). We also investigate the function(s) of the LEM domain proteins, Heh1 and Heh2, on various aspects of nuclear cell biology including genome stability (see Current Research). In a new collaborative project with the Lusk Lab (medicine.yale.edu/lab/lusk/), we are defining the fundamental mechanisms that underlie nuclear integrity and nuclear envelope repair, which has important implication for cancer development and treatment. Working with our collaborator Simon Mochrie (Physics), we are defining the physical role that chromatin plays in defining nuclear mechanics, which we investigate in vitro using isolated nuclei and force spectroscopy and live cell imaging (see Current Research). Recently we have initiated a new project to leverage the fission yeast model to define the fundamental mechanisms underlying the folding of the genome using a combination of live cell imaging, sophisticated image analysis, and polymer modeling in collaboration with Simon Mochrie and Corey O'Hern (Engineering).
Work in our lab is supported by NIH/NIGMS and the NSF.
We are currently recruiting new members to join our team. If you are interested, please see the Lab Members tab!