Control of cellular resource allocation across biological scales in microorganisms

项目摘要 稳态是所有细胞生理控制的基本特征。在过去的五年里，新 由我们共同发现稳态原理改变了我们对细胞大小控制的看法。这一原则， 被称为“加法器”，指出细胞在出生和分裂之间增加固定的大小，而不管细胞的大小。 出生因此，加法器原理由于其被动性质而不同于许多生物控制，因为 加法器样细胞不使用任何明显的大小感应或反馈机制来触发分裂， 它们达到一个固定的临界尺寸。该计划是我们在细胞大小控制方面成功的延伸 研究以了解更广泛的生理控制类别。 首先，我们将研究负责生理过程的精确性和鲁棒性的机制。 我们将专注于细菌中的复制起始，因为它可以作为一个易于处理的模型来解决这些长期的问题。 存在的问题。生理控制的另一个重要方面是细胞如何分配资源， 增长目前的研究范式是基于E.大肠杆菌是细胞平衡氨基酸的供应和需求， 在所有生长条件下，最大化生长速率。这些模型很重要，因为它们能够 来解释细胞能量的产生与蛋白质的产生之间的权衡， 癌然而，我们已经在B中获得了实验结果。枯草杆菌直接挑战了这种E.大肠着丝粒的 控制增长的观点。因此，我们将寻求蜂窝资源分配的更一般的原则， 包括E. coli和B.枯草杆菌，理想的是超越细菌。最后，我们将扩展我们以前的工作， 细胞大小控制，研究细胞如何确保生理平衡时，蛋白质和细胞器 分区不对称，这在遗传和细胞老化的背景下很重要。 这些问题需要从生理学到新技术开发的多学科方法。 为此，我们将与谁是在他们的研究领域的领导者合作。此外，在A 十年来，我们一直在努力使研究界的技术民主化。我们预计 知识和技术，将产生从我们提出的研究，以打开令人兴奋的新 研究途径和促进生理学和细胞生物学的其他重要发现。

Project Summary Homeostasis is a fundamental feature of physiological control in all cells. In the past five years, a new homeostatic principle co-discovered by us has been changing our view of cell-size control. This principle, known as the “adder”, states that cells add fixed size between birth and division irrespective of the cell size at birth. The adder principle is therefore distinct from many biological controls due to its passive nature, as the adder-like cells do not employ any apparent size sensing or feedback mechanisms to trigger division when they reach a fixed critical size. The proposed program is an extension of our success in cell-size control research to understand a broader class of physiological controls. First, we will study the mechanisms responsible for the precision and robustness of physiological processes. We will focus on replication initiation in bacteria as it can serve as a tractable model to solve these long- standing problems. Another important aspect of physiological control is how cells allocate their resources to growth. The current paradigm based on E. coli is that cells balance supply and demand of amino acids to maximize growth rate under all growth conditions. These models are important because they have been able to explain the tradeoff between production of cellular energy vs. production of proteins that is pertinent to cancer. However, we have obtained experimental results in B. subtilis that directly challenged this E. coli centric view of growth control. We will thus seek more general principles of cellular resource allocation that encompass both E. coli and B. subtilis, and ideally beyond bacteria. Finally, we will extend our previous work on cell-size control to investigate how cells ensure physiological equilibrium when proteins and organelles partition asymmetrically, which is important in the context of inheritance and cellular aging. These questions require multidisciplinary approaches from physiology to development of novel technologies. To this end, we will work with collaborators who are leaders in their research fields. Furthermore, over a decade we have been making major efforts to democratize technologies to the research community. We expect the knowledge and technology that will be generated from our proposed research to open exciting new research avenues and facilitate other important discoveries in physiology and cell biology.