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

新陈代谢是提供能量、分子构件和化学信号以控制生命必需的细胞功能的生化过程。凭借该奖项，化学部的生命过程化学项目正在资助弗吉尼亚大学的 Ku-Lung (Ken) Hsu 博士研究单个细胞如何控制脂肪和脂质的代谢。许博士正在开发新型化合物，这些化合物附着在酶（蛋白质催化剂）上，以探测细胞内脂肪和脂质的代谢。这些探针根据细胞的代谢状态阐明细胞如何相似或不同。揭示大量细胞中独特的代谢特性表明看似相同的细胞如何分化为特定的细胞类型（例如神经细胞与肌肉细胞）。通过这些研究发现的代谢信号可能有助于开发新的细胞类型或特性，从而突破细胞工程的界限。研究生接受化学和化学生物学方面的独特培训，以培养他们成为社会的杰出领导者和榜样。该研究项目与一项教育推广计划相结合，旨在通过教授脂质（生物）化学如何影响社会中的健康食物选择和饮食行为，广泛影响美国原住民学生社区。该研究计划旨在了解单细胞水平上细胞功能的代谢调节。这些研究的意义在于建立对相同细胞如何分化成功能不同的细胞谱系的基本理解。该假设认为，新陈代谢通过提供指定细胞功能和命运的基本化学信号来赋予不对称性。小分子报告基因与流式细胞术集成，以前所未有的分子分辨率对数百万个活细胞的动态代谢调节进行大规模并行分析。将代谢建立为细胞生物学不对称规范的机制揭示了全新的细胞表型，并对细胞生物学和工程产生更广泛的影响。因此，这些研究是建立用于单细胞分析的化学探针的基础，这些探针可以与现代“组学”方法相结合，为高分辨率探测细胞功能开辟新的机会。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.