Organelle segregation & quality control during gametogenesis
Extensive cellular remodeling in the form of organelle morphogenesis, membrane biogenesis as well as protein and organelle degradation occurs during gametogenesis, yet we know very little about the underlying principles of these events. While each process itself inspires a number of cell biological questions to uncover, a broad understanding of this cellular restructuring program is especially important, given our finding that gametogenesis leads to elimination of age-induced cellular damage in budding yeast. Examples of such damage include the extrachromosomal circles that arise from illegitimate recombination at the ribosomal DNA locus, protein aggregates that associate with the chaperone Hsp104 and morphological aberrations of the nucleoli (Ünal et al., 2011). We found that gametes no longer contained any of the cellular defects that were present in the aged precursor cells.
By employing live imaging and conditional genetic screens, we aim to obtain both dynamic and comprehensive insights into the cellular remodeling processes that occur during gametogenesis. We are specifically interested in the aspects of nucleolar physiology and protein homeostasis that are susceptible to aging and determining how meiotic cells effectively eliminate protein aggregation and remodel their nucleoli. In collaboration with the Kimble Lab at the University of Wisconsin Madison, we also started to build some imaging tools in the roundworm C. elegans with the hope of extending our studies to a metazoan model system.