Real-Time Imaging of metabolic Communication

描述(申请人提供)：代谢交换是一种普遍现象。从细菌这样简单的生物到人类等复杂的高等真核生物，它对每一个有机体都是必不可少的。虽然代谢交换使人体内约70万亿个细胞之间的合作和协调成为可能，但即使是单细胞生物也依赖代谢交换来适应环境压力，形成生物膜。细胞通讯使干细胞分化，癌细胞增殖，神经元燃烧，细菌感知法定人数，病原体在人类宿主中存活。用于通信的分子的化学多样性是非同寻常的，包括钙等小离子，次级代谢物、脂肪酸、多肽等小分子，但也包括碳水化合物、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描述细胞之间的交流，更不用说实时了。在这项提案中，我们的重点将放在解吸电喷雾质谱仪的应用和适应上，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。我们的目标是同时在空间和时间上实现这一点。这些工具将提高我们对分泌性生物标记物、微生物组与人类细胞相互作用的理解，以及对不同类型细胞(例如，杆菌与巨噬细胞、中性粒细胞或T细胞)之间的合作以及跨界交流所产生的传染病的复杂性的理解。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系统范围内涉及细胞间代谢通讯的范例。 公共卫生相关性：该提案旨在开发参与病原体-免疫细胞群体代谢交换的分子实体的实时监测。我们将不同细胞群之间的代谢交换“可视化”的能力可能会导致新的治疗范例。

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.