Title: How big is big enough? Cell size and commitment to division in budding yeast
Speaker: Michael Tyers, Samuel Lunenfeld Research Institute, University of Toronto
Date: Wednesday, May 5, 2004, 1:00 pm
Location: Hill Center, Room 260, Rutgers University, Busch Campus, Piscataway, NJ
Genome-wide approaches to discovery of gene function include systematic analysis of gene expression, deletion phenotypes and protein interactions. More than any single approach, each of which is subject to caveats in interpretation and/or reproducibility, the intersection of orthogonal large-scale datasets provides a robust means to interrogate gene function. We applied an integrated functional genomics approach to the long-standing issue of cell size homeostasis in budding yeast, a problem which has been largely refractory to conventional genetics. Before commitment to cell division in late G1 phase, an event called Start in yeast, cells must achieve a minimum critical cell size. To uncover new pathways that coordinate growth and division at Start, we determined the cell size phenome of ~6000 gene deletion strains by direct size analysis and by barcode array analysis of size selected populations. Hierarchical clustering of size profiles identified hundreds of small (whi) or large (lge) mutants, which were partially ordered by size epistasis. Novel genes that potently affect cell size include a formal genetic equivalent of the retinoblastoma tumor suppressor, called Whi5, and a kinase-transcription factor network that controls expression of a massive ribosome biogenesis (RiBi) regulon composed of >200 genes. The former result harmonizes the yeast and metazoan cell cycle machineries, while the latter findings suggest that it is the process of building ribosomes, rather than protein synthetic rate per se, that determines the timing of cell cycle commitment. In toto, over 40 new genes that regulate cell size have been identified, thus demonstrating the power of an integrated genomics approach to unravel complex biological processes.
Seminar sponsored by DIMACS/BIOMAPS Seminar Series on Quantitative Biology and Epidemiology.