Real-Time Imaging of metabolic Communication

描述（由申请人提供）：代谢交换是一种普遍现象。从简单的细菌到复杂的高等真核生物（如人类），它对每一种生物都是必不可少的。代谢交换使人类平均约70万亿个细胞之间的合作和协调成为可能，即使是单细胞生物也依靠代谢交换来适应环境压力并形成生物膜。细胞间的交流使干细胞能够分化，癌细胞能够增殖，神经元能够放电，细菌能够感应数量，病原体能够在人类宿主体内存活。用于交流的分子的化学多样性是非凡的，包括小离子，如钙，小分子，如次级代谢物，脂肪酸，肽，还有碳水化合物，蛋白质和核酸。尽管代谢交换具有普遍性，但很少有方法能够以系统和敏感的方式表征细胞之间的通信，更不用说实时了。在本提案中，我们的重点将放在解吸电喷雾质谱的应用和适应上，以实现实时活细胞检测以及重要生物过程中代谢交换的表征和可视化。我们的目标是在空间和时间上实现这一目标。这些工具将提高我们对分泌生物标志物、微生物组与人类细胞相互作用的理解，并理解来自不同类型细胞（如杆菌与巨噬细胞、中性粒细胞或t细胞）之间合作和界间交流的传染病的复杂性。最终，它可能会推动新的治疗策略或干预措施的发展，这些治疗策略或干预措施基于全系统范围内细胞间代谢通讯的范式。

DESCRIPTION (provided by applicant): Metabolic exchange is a universal phenomenon. It is essential to every organism, from those as simple as bacteria to complex higher eukaryotes such as humans. While metabolic exchange enables cooperation and coordination between the ~70 trillion cells in an average human being, even unicellular organisms rely on metabolic exchange to adapt to environmental stress and form biofilms. Cellular communication allows stem cells to differentiate, cancer cells to proliferate, neurons to fire, bacteria to sense a quorum and pathogens to survive in human hosts. The chemical diversity of the molecules used for communication is extraordinary, and includes small ions such as calcium, small molecules such as secondary metabolites, fatty acids, peptides, but also carbohydrates, proteins and nucleic acids. Despite the universal nature of metabolic exchange, there are few methods that can characterize the communication between cells in a systematic and sensitive fashion, let alone real-time. In this proposal, our focus will be on the application and adaptation of desorption electrospray mass spectrometry to enable the real-time live cell detection and the characterization and visualization of metabolic exchange in important biological processes. We aim to accomplish this in both a spatial as well as temporal fashion. These tools will improve our understanding of secreted biomarkers, microbiome-human cell interactions and understanding the complexities of infectious disease that derive from the cooperation between different types of cells (e.g. Bacilli with macrophages, neutrophils or T-cells) and interkingdom communication. Ultimately it may drive the development of new therapeutic strategies or interventions based on paradigms involving inter-cellular metabolic communication in a system wide fashion. PUBLIC HEALTH RELEVANCE: This proposal aims to develop real-time monitoring of molecular entities involved in metabolic exchange of pathogen-immunological cell populations. Our ability to "visualize" metabolic exchange between different cell populations could lead to new therapeutic paradigms.