In living cells, proteins rarely act alone but rather interact with each other to perform their function. Further, groups of proteins associate physically at the same time and place to form protein complexes, assemble intracellular structures, and orchestrate essential cellular processes. We are interested in understanding how proteins (in nanometer size) work together, organize intracellular structures (in micron length scale), and carry out many aspects of cellular functions.
Cell division is an essential and complex cellular process, involving dramatic reorganization of intracellular structures and requiring precise coordination of spatial and temporal events. Cell division gone awry is a hallmark of human cancers. To ensure error-free cell division, chromosomes need to accurately segregate into daughter cells, accomplished by the proper assembly of an ellipsoidal mitotic spindle. The mitotic spindle is composed of dynamic microtubules, polar polymers of α, β tubulin. Distinct microtubule-associated proteins are needed to temporally regulate microtubule nucleation and organize microtubules to form the mitotic spindle. Spatial coordination of orientation and position of the mitotic spindle is also tightly controlled in order for proper segregation of two daughter cells. Currently, cell biological and proteomics studies have produced a nearly complete 'parts-list' for these mitotic processes. However, how these parts work in concert to organize and position the spindle machinery remains unclear.
Our major goal is to elucidate, in atomic detail, the molecular mechanisms underlying microtubule organization, microtubule nucleation and spindle positioning during cell division. Our recent work has particularly focused on how microtubule-associated proteins (e.g. hetero-octameric augmin protein complex and nuclear mitotic apparatus (NuMA)) regulate microtubule nucleation and microtubule organization. To gain insight into the molecular mechanisms of these proteins, we will apply interdisciplinary approaches to (1) reconstitute a minimal system using purified components (biochemical and molecular biology techniques), (2) determine their static snapshots (structural approaches), and (3) examine their dynamic properties (biophysical and cell biological methods).