Transitions: Spatiotemporal Behaviors of Metabolic Fluxes in Cell Biology

新陈代谢提供活细胞生长、移动和建立内部结构所需的能量和物质。代谢通量，即通过代谢途径的分子周转率，已知在细胞之间和细胞内表现出空间和时间上的差异，但这种异质性仍然知之甚少。在这个项目中，PI将接受培训并进行研究，使他能够过渡，以便在他的实验室中投入大量精力研究细胞生物学中代谢通量的时空行为。所获得的知识可能有助于了解代谢缺陷如何破坏细胞分裂、生长和亚细胞组织。这项工作的更广泛影响包括研究的内在优点，因为所有细胞都经历代谢通量和破坏可能导致不同的病理。此外，研究生、本科生和高中生将通过参与项目、课堂、暑期课程和辅导课，接受跨学科研究方面的培训。高中学生和普通公众将有机会使用研究级显微镜来检查藻类的生长和行为，并了解单细胞生物与环境之间的联系。这个项目将使PI能够将他的研究重点转移到化学、物理和生物学之间的一个新领域：代谢通量时空变化的本质、原因和后果。在项目的专业发展部分，PI和他的实验室成员将学习两种测量代谢通量的技术：质谱和受激拉曼散射（SRS）显微镜。在该项目的研究部分，他们将使用这些技术，以及荧光显微镜和粗粒度理论，研究：1)基因表达对大肠杆菌代谢通量的时间和细胞间变化的影响，以及2)小鼠卵母细胞线粒体代谢和代谢通量的亚细胞变化。这项工作的长期目标是发展变革性的方法和预测理论，为生物自组织和控制生命过程的规则提供见解。这项工作得到了细胞动力学和功能集群以及分子和细胞生物科学部的系统和合成生物学集群的支持。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Metabolism supplies the energy and material that living cells use to grow, move, and establish their internal structure. Metabolic fluxes, the rate of turnover of molecules through metabolic pathways, are known to exhibit spatial and temporal variations between cells and within cells, but such heterogeneities remain poorly understood. In this project, the PI will obtain training and perform research that will enable him to transition so that a significant effort in his laboratory is dedicated to studying the spatiotemporal behaviors of metabolic fluxes in cell biology. The knowledge gained may help lead to an understanding of how metabolic defects disrupt cell division, growth, and subcellular organization. The Broader Impacts of the work include the intrinsic merit of the research as all cells undergo metabolic flux and disruptions can lead to diverse pathologies. In addition, graduate students, undergraduates, and high school students will be trained in interdisciplinary research, both through working on the project, and in classes, summer courses, and tutorials. High school students, and members of the general public, will be given the opportunity to use research grade microscopes to examine the growth and behaviors of algae, and to learn about the connection between single cell organisms and the environment.This project will enable the PI to shift the focus of his research to a new area at the interface between chemistry, physics, and biology: the nature, causes, and consequences of spatiotemporal variations in metabolic fluxes. In the professional development portion of the project, the PI, and members of his lab, will learn two techniques for measuring metabolic fluxes: mass spectroscopy and stimulated Raman scattering (SRS) microscopy. In the research portion of the project, they will use these techniques, along with fluorescence microscopy and coarse-grained theories, to study: 1) the impact of gene expression on temporal and cell-to-cell variation of metabolic fluxes in E. coli, and 2) subcellular variations in mitochondrial metabolism and metabolic fluxes in mouse oocytes. The long-term goal of this work is to develop transformative methods and predictive theories that will provide insights into biological self-organization and the rules governing life's processes. This work is supported by both the Cellular Dynamics and Function Cluster, along with the Systems and Synthetic Biology Cluster in the Division of Molecular and Cellular Biosciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.