The primary focus of our funded research is to determine the regulatory mechanisms that govern and maintain meiotic commitment using budding yeast as a model organism. An exogenous signal induces cells to sequentially enter meiosis and then differentiate into gametes. Our studies seek to determine how cells integrate external signals with intracellular regulatory networks to commit to meiosis or to maintain meiotic commitment if the signal is removed or replaced by a mitosis-inducing signal. Our main goals are to identify the cell-cycle regulators that govern meiotic commitment, determine how the regulators function within the network, and determine how checkpoint mechanisms monitor meiotic commitment. Our results will uncover general mechanisms of cell-cycle regulation in both mitosis and meiosis. An essential tool for our studies is the use of time-lapse microscopy. We developed a microfluidics assay to manipulate cells? external signals as we are monitoring meiotic commitment in individual cells with time-lapse microscopy. This assay is a powerful tool to allow us to dissect the cell-cycle regulatory mechanisms of meiotic commitment. By studying individual cells, we can more precisely identify cells that fail to maintain meiotic commitment in the presence of mitosis-inducing signals. And, we can identify perturbations in meiotic duration in different mutant backgrounds. In this supplement proposal, I am requesting funds for the replacement of my aging microscope system, with a Nikon eclipse Ti2. Our system has served us well, but is no longer reliable and is likely near the end of its lifetime. The Nikon eclipse Ti2 will allow us to perform the time-lapse imaging for the experiments proposed.
The proposed studies are designed to uncover general mechanisms of meiotic and mitotic cell-cycle control. These studies are relevant to public health because they will reveal how errors in meiotic and mitotic cell-cycle regulation cause tumor formation and developmental defects. In this supplement proposal, I am requesting a Nikon eclipse Ti2 microscope system to undertake the proposed experiments.
| Gihana, Gabriel M; Musser, Tiffany R; Thompson, Oscar et al. (2018) Prolonged cyclin-dependent kinase inhibition results in septin perturbations during return to growth and mitosis. J Cell Biol 217:2429-2443 |
| Lacefield, Soni (2017) Chromosome Biology: Specification of the Kinetochore for Cohesin Recruitment. Curr Biol 27:R1319-R1321 |
| Yang, Yang; Lacefield, Soni (2016) Bub3 activation and inhibition of the APC/C. Cell Cycle 15:1-2 |
| Falk, Jill Elaine; Tsuchiya, Dai; Verdaasdonk, Jolien et al. (2016) Spatial signals link exit from mitosis to spindle position. Elife 5: |
| Yang, Yang; Tsuchiya, Dai; Lacefield, Soni (2015) Bub3 promotes Cdc20-dependent activation of the APC/C in S. cerevisiae. J Cell Biol 209:519-27 |
| Ho, Kung-Hsien; Tsuchiya, Dai; Oliger, Audrey C et al. (2014) Localization and function of budding yeast CENP-A depends upon kinetochore protein interactions and is independent of canonical centromere sequence. Cell Rep 9:2027-33 |
