The Biogenesis and Survival of Vegetative, Quiescent Yeast Cells

静止是地球上细胞的一种普遍状态，但人们对它知之甚少。静止细胞，从不可培养的微生物到结核分枝杆菌和干细胞，在所有物种的生存中发挥着重要作用。沃纳-沃什伯恩博士及其同事最近发现，当酵母菌落耗尽葡萄糖时，培养中的细胞会经历不对称的细胞分裂，从而产生静止的子细胞和非静止的母细胞。静止细胞和非静止细胞之间的生理和形态差异是显著的，并且使人想起在其他静止细胞（如神经元和干细胞）的产生中所看到的分化。本研究项目将通过对mRNA转录丰度变化的时间过程分析和该过程所需基因的鉴定来研究葡萄糖耗竭后的细胞分裂。mRNA将使用基于寡核苷酸的微阵列进行研究。静止和非静止细胞形成和存活所需的基因将使用由大约6000个酵母菌株组成的酵母菌缺失集进行鉴定，每个酵母菌株都携带一个特定基因的缺失。表征mRNA水平和突变体的变化将有助于更好地理解营养、静止酵母细胞的发育。它还将有助于更好地理解这种不对称细胞分裂的进化保护，从而更好地理解这种细胞分裂在所有生物体中产生静止细胞的作用。这项工作的广泛影响来自Werner-Washburne实验室的跨学科互动，与计算机科学和数学的密切合作，以及来自本科生，研究生和博士后水平的代表性不足群体的学生的培训。

Quiescence is a poorly understood but universal state of cells on earth. Quiescent cells, from unculturable microbes to M. tuberculosis and stem cells, play important roles in the survival of all species. Dr. Werner-Washburne and co-workers have recently discovered that when yeast colonies exhaust glucose, cells in the culture undergo an asymmetric cell division leading to the production of a quiescent daughter cell and non-quiescent mother cell. The physiological and morphological differences between the quiescent and non-quiescent cells are remarkable and are reminiscent of the differentiation seen in the production of other quiescent cells, such as neurons and stem cells. This research project will examine the cell division after glucose exhaustion through a time-course analysis of changes in mRNA transcript abundance and identification of genes required for this process. mRNA will be studied using oligonucleotide-based microarrays. Genes required for the formation and survival of quiescent and non-quiescent cells will be identified using a yeast deletion set composed of approximately 6000 yeast strains, each carrying a deletion in a specific gene. Characterization of the changes in mRNA levels and mutants will lead to a better understanding of the development of vegetative, quiescent yeast cells. It will also lead to a better understanding of the evolutionary conservation of this asymmetric cell division and, thus, the role of this cell division in the production of quiescent cells in all organisms. The broader impact of this work comes from the cross-disciplinary interactions in the Werner-Washburne laboratory, with close collaborations in computer sciences and math, and from training of students from under-represented groups at the undergraduate, graduate and post doctoral levels.