Scaling of transcript abundance with cell size and the commitment to cell division

项目总结/摘要 所有单元都必须增长到一个最小大小-“临界大小”，然后才能提交到单元 师.这种尺寸要求防止细胞变得太大或太小，并协调 分裂伴随细胞大量生长。作为尺寸控制的结果，细胞具有窄的和 细胞大小的特征性分布，即大小稳态。尽管经过了几十年的研究， 不知道细胞如何测量和响应大小，或者为什么机械地最小尺寸是 对组织的承诺。这项资助的第一个学期表明，随着酵母细胞的生长， 在大小上，数以百计的mRNA系统地表达在越来越高的水平上，它们 丰度的增加快于细胞大小的增加，因此它们的浓度增加。 这被称为“超级缩放”。其他的mRNAs则相反，它们的增长速度比 尺寸增加和浓度降低--称为“亚尺度”。引人注目的是， 激活细胞周期的基因属于第一组，而抑制细胞周期的基因属于第二组。 第二组。这立即提出了用于细胞大小控制的“缩放”模型， 稳态：激活剂与抑制剂的比例随着G1期细胞的生长而增加，并且在G1期细胞中， 足够高浓度的激活剂，抑制剂被克服，细胞致力于 师.控制细胞大小的“sizer”是产生差异缩放的机制， 基因表达。在这里，将测试这一想法的关键方面。将开发一个系统， 精确测量基因表达的比例。将开发一个系统， 测量细胞在分裂时大小的变化。最重要的是，这些新- 开发的分析将用于测试几种假设的机制，基因是如何被发现的。 差异表达的大小。“缩放”模型的一般性将得到解决。 最后，将考虑在翻译层面也发生缩放的可能性。

Project Summary/Abstract All cells must grow to a minimum size—the “critical size”—before they can commit to cell division. This size requirement prevents cells from becoming too big or small, and co-ordinates division with cell growth in mass. As a consequence of size control, cells have narrow and characteristic distributions of cell size—that is, size homeostasis. Despite decades of study, it is unknown how cells measure and respond to size, or why mechanistically a minimum size is required for commitment to division. The first term of this grant showed that as yeast cells grow in size, hundreds of mRNAs are systematically expressed at higher and higher levels—they increase in abundance faster than the increase in cell size, and so they increase in concentration. This is termed “super-scaling”. Other mRNAs do the opposite—they increase slower than the increase in size, and decrease in concentration—termed “sub-scaling”. Strikingly, genes that activate the cell cycle fall into the first group, while genes that inhibit the cell cycle fall into the second group. This immediately suggests a “Scaling” model for cell size control and homeostasis: the ratio of activators to inhibitors increases as G1 phase cells grow, and at a sufficiently high concentration of activators, inhibitors are overcome, and cells commit to division. The “sizer” that controls cell size is the mechanism that produces differential scaling of gene expression. Here, key aspects of this idea will be tested. A system will be developed for accurately measuring scaling of gene expression. A system will be developed for accurately measuring the variation in cell size at commitment to division. Most importantly, these newly- developed assays will be used to test several hypotheses for the mechanism by which genes are differentially expressed with size. The generality of the “Scaling” model will be addressed. Finally, the possibility that scaling is also occurring at the level of translation will be considered.