CAREER: Next-Generation Flow Cytometry - A New Approach to Cell Heterogeneity

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Metabolism is the biochemical process that supplies energy, molecular building blocks, and chemical signals to control cellular functions essential for life. With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Ku-Lung (Ken) Hsu from the University of Virginia to investigate how individual cells control the metabolism of fats and lipids. Dr. Hsu is developing novel chemical compounds that attach to enzymes (protein catalysts) to probe the metabolism of fats and lipids inside of cells. These probes illuminate how cells are similar or distinct based on their metabolic status. Uncovering distinctive metabolic identities within a massive assortment of cells shows how seemingly identical cells differentiate into specific cell types (e.g. a nerve versus a muscle cell). The metabolic signals discovered through these studies may enable the development of new cell types or properties to push the boundaries of cell engineering. Graduate students receive unique training in chemistry and chemical biology to foster their development as outstanding leaders and role models in society. The research project is integrated with an educational outreach program designed to broadly impact Native American students communities by teaching how lipid (bio)chemistry influences healthy food choices and eating behaviors in society.This research program aims to understand metabolic regulation of cellular function at the single-cell level. The significance of the studies is to establish a fundamental understanding of how identical cells differentiate into functionally distinct cell lineages. The hypothesis is that metabolism imparts asymmetry by providing essential chemical signals that specify a cell's function and fate. Small molecule reporters are integrated with flow cytometry for massively parallel analysis of dynamic metabolic regulation across millions of live cells with unprecedented molecular resolution. Establishing metabolism as a mechanism for asymmetrical specification of cell biology reveals completely new cell phenotypes and has broader impacts in cell biology and engineering. Thus, the research studies are foundational for establishing chemical probes for single-cell analysis that can be combined with modern "omics" methods to open new opportunities for probing cellular function with high resolution.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.