Control of cellular resource allocation across biological scales in microorganisms

微生物跨生物尺度的细胞资源分配控制

• 批准号: 10415026
• 负责人: Suckjoon Jun
• 金额: $ 39.5万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10415026
• 关键词: Amino Acids; Bacillus subtilis; Bacteria; Biological; Birth; Cell Aging; Cell Cycle; Cell Size; Cells; Cellular biology; Communities; Development; Disease; Ensure; Equilibrium; Escherichia coli; Feedback; Gene Expression; Gene Proteins; Goals; Growth; Homeostasis; Knowledge; Malignant Neoplasms; Microbial Physiology; Modeling; Nature; Normal Cell; Organelles; Physiological; Physiological Processes; Physiology; Production; Proteins; Regulation; Replication Initiation; Research; Resource Allocation; Resources; Technology; Work; base; interdisciplinary approach; microorganism; new technology; programs; success

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.

项目概要 体内平衡是所有细胞生理控制的一个基本特征，在过去的五年里出现了一个新的特征。 我们共同发现的稳态原理正在改变我们对细胞大小控制的看法。 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，无论细胞大小如何 因此，由于其被动性质，加法器原理与许多生物控制不同。 类似加法器的细胞不采用任何表观尺寸传感或反馈机制来触发分裂 它们达到了固定的临界尺寸。所提出的计划是我们在单元尺寸控制方面的成功的延伸。 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精确性和稳健性的机制。 我们将重点关注细菌的复制起始，因为它可以作为解决这些长期问题的易于处理的模型。 生理控制的另一个重要方面是细胞如何分配资源。 当前基于大肠杆菌的范例是细胞平衡氨基酸的供应和需求。 这些模型很重要，因为它们能够在所有生长条件下最大化增长率。 解释细胞能量生产与蛋白质生产之间的权衡 然而，我们在枯草芽孢杆菌中获得了直接挑战这种以大肠杆菌为中心的实验结果。 因此，我们将寻求更通用的蜂窝资源分配原则。 包括大肠杆菌和枯草芽孢杆菌，最好不包括细菌。最后，我们将扩展我们之前的工作。 细胞大小平衡控制，研究当蛋白质和细胞器时细胞如何确保生理 不对称分配，这在遗传和细胞衰老的背景下很重要。 这些问题需要从生理学到新技术开发的多学科方法。 为此，我们将与各自研究领域的领导者合作。 十年来，我们一直在努力使研究界的技术民主化。 我们提出的研究将产生知识和技术，以开启令人兴奋的新领域 研究途径并促进生理学和细胞生物学的其他重要发现。