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所必需的细胞功能的生化过程。通过这一奖项，化学系的生命过程化学项目资助弗吉尼亚大学的Ku-loong(Ken)Hsu博士研究单个细胞如何控制脂肪和脂类的代谢。许博士正在开发附着在酶(蛋白质催化剂)上的新型化合物，以探测细胞内脂肪和脂类的新陈代谢。这些探针阐明了细胞如何根据其代谢状态而相似或不同。发现大量细胞中独特的新陈代谢特征，显示了看似相同的细胞如何分化为特定类型的细胞(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会使新细胞类型或特性的开发突破细胞工程的界限。研究生接受独特的化学和化学生物学方面的培训，以培养他们作为社会杰出领导者和榜样的发展。该研究项目与一个教育推广项目相结合，旨在通过教授脂质(生物)化学如何影响社会中健康的食物选择和饮食行为来广泛影响美国原住民学生社区。该研究项目旨在了解单细胞水平上细胞功能的新陈代谢调节。这些研究的意义是建立一个基本的理解，即相同的细胞如何分化成功能不同的细胞系。假说是，新陈代谢通过提供指定细胞功能和命运的基本化学信号而产生不对称性。小分子报告器与流式细胞仪相结合，以前所未有的分子分辨率对数百万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一种机制，揭示了全新的细胞表型，并在细胞生物学和工程学中具有更广泛的影响。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，为以高分辨率探测细胞功能开辟新的机会。这一奖项反映了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.