CAREER: Cell Size and Cell Cycle Control in the Presence of Fluctuations in Bacteria

职业：细菌存在波动时的细胞大小和细胞周期控制

• 批准号: 1253843
• 负责人: Suckjoon Jun
• 金额: $ 114.54万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1253843&HistoricalAwards=false
• 关键词: CAREER; Cell; Size; Cycle; Control

Intellectual Merit An exquisite, quantitative relationship between growth and cell cycle exists in bacteria. Strikingly, the onset of DNA replication is assumed to coincide with achievement of a specific cell mass (critical mass), a phenomenon that is independent of growth rate. This was one of the most important quantitative ideas in the field of bacterial physiology during the 1950s and the 1960s, and it still serves as the foundation for our current understanding of cell cycle control. Surprisingly, however, we do not yet understand how the molecular-level regulation controls the global relationship between growth and cell cycle. To this end, this project will employ state-of-the-art microscopy to visualize replication and cell division machinery in living cells, allowing us to precisely measure cell growth, DNA replication and cell division timing. In particular, the project will study how the cell responds to physiological perturbations at the single-cell level. Single-cell approach is important, because we can acquire critical molecular-level information related to intracellular fluctuations that is inevitably lost in population-level studies. Importantly, this project will employ two evolutionarily divergent model organisms, Escherichia coli and Bacillus subtilis, permitting us to determine which aspects of cell cycle regulation are likely to be broadly conserved. In doing so, this project will provide a definitive answer to the fundamental question of whether or not cells grow to a critical cell mass to initiate a specific cell-cycle event. The strength of this research lies in its ability to bridge the gap between experiment and theory. In addition to the experimental component described above, the theory component involves quantitative modeling of the acquired data to make experimentally testable predictions. The outcome of the research will have implications for our fundamental understanding of the growth of all cells.Broader Impacts Quantitative biology is more than adding numbers to what biologists already know. The power of the approach is to bring quantitative rigor from physical sciences to identify and solve important and interesting problems in biology. As part of the new initiative of quantitative biology at the University of California at San Diego, the project aims to spread the culture of quantitative approaches to biology from K12 to graduate level education in the San Diego area. This integrative project places great emphasis on the importance of interdisciplinary research experiences at the undergraduate level. To inspire not only the students and educators but also the general public, an annual summer interdisciplinary research bootcamp will be offered for undergraduate students, and possibly senior high-school students, in the San Diego area. Students from under-represented minority groups will be particularly encouraged to participate, and a Hispanic Serving Institution (San Diego State University) will collaborate in the project. A former instructor from the Cold Spring Harbor Laboratory Courses joins the project to design and co-teach the bootcamp modules that incorporate molecular biology, quantitative microscopy, microfluidics, and image analysis. The overall goal is to design exemplary undergraduate research modules and integrate them into standard undergraduate research curricula in quantitative biology at UCSD, SDSU, and other universities. This award is cofounded by the programs in Cellular Dynamics and Function and the Physics of Living Systems.

智力优势 细菌的生长和细胞周期之间存在着微妙的定量关系。引人注目的是，DNA复制的开始被认为与特定细胞质量（临界质量）的实现相一致，这是一种与生长速率无关的现象。这是20世纪50年代和60年代细菌生理学领域最重要的定量思想之一，它仍然是我们目前理解细胞周期控制的基础。然而，令人惊讶的是，我们还不知道分子水平的调节如何控制生长和细胞周期之间的整体关系。为此，该项目将采用最先进的显微镜来可视化活细胞中的复制和细胞分裂机制，使我们能够精确测量细胞生长、DNA复制和细胞分裂时机。特别是，该项目将研究细胞如何在单细胞水平上对生理扰动作出反应。单细胞方法很重要，因为我们可以获得与细胞内波动相关的关键分子水平信息，这些信息在群体水平研究中不可避免地丢失。重要的是，该项目将采用两种进化上不同的模式生物，大肠杆菌和枯草芽孢杆菌，使我们能够确定细胞周期调控的哪些方面可能是广泛保守的。在这样做的过程中，该项目将为细胞是否生长到临界细胞质量以启动特定细胞周期事件的基本问题提供明确的答案。 这项研究的优势在于它能够弥合实验和理论之间的差距。除了上述实验部分之外，理论部分还涉及对所获取的数据进行定量建模，以做出可实验测试的预测。这项研究的结果将对我们从根本上理解所有细胞的生长产生影响。 定量生物学不仅仅是在生物学家已经知道的基础上增加数字。这种方法的力量是从物理科学中引入定量的严谨性，以识别和解决生物学中重要而有趣的问题。作为圣地亚哥加州大学定量生物学新举措的一部分，该项目旨在将定量生物学方法的文化从K12传播到圣地亚哥地区的研究生教育。这个综合项目非常强调本科阶段跨学科研究经验的重要性。为了激励不仅是学生和教育工作者，也是广大公众，每年夏季跨学科研究训练营将提供给本科生，并可能高中学生，在圣地亚哥地区。 将特别鼓励代表性不足的少数群体的学生参加，一个西班牙裔服务机构（圣地亚哥州立大学）将在该项目中合作。一位来自冷泉港实验室课程的前讲师加入了该项目，设计并共同教授包含分子生物学、定量显微镜、微流体和图像分析的训练营模块。总体目标是设计示范性本科研究模块，并将其整合到UCSD，SDSU和其他大学的定量生物学标准本科研究课程中。 该奖项由细胞动力学和功能以及生命系统物理学课程共同创立。