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.

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Harvard University
United States
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