Resource for Quantitative Elemental Mapping for the Life Sciences

生命科学定量元素图谱资源

• 批准号: 10494054
• 负责人: Chris Johnson Jacobsen
• 金额: $ 96.24万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10494054
• 关键词: Address; Advisory Committees; Affect; Animals; Automobile Driving; Biological; Biological Markers; Biological Process; Biological Sciences; Biology; Biomedical Research; Brain; Cell Cycle; Cell Extracts; Cell physiology; Cells; Chemicals; Chemistry; Collaborations; Communities; Computer software; Coordination and Collaboration; Copper; Core Facility; Country; Data; Development; Diagnosis; Disease; Ecosystem; Elements; Emerging Technologies; Engineering; Faculty; Fluorescence Microscopy; Fostering; Genes; Goals; Growth; Health; Human; Human Genome; Image; Inductively Coupled Plasma Mass Spectrometry; Infection; Infrastructure; Inorganic Chemistry; Institutes; Ions; Iron; Laboratories; Leadership; Life; Link; Location; Mammalian Cell; Maps; Metabolic; Metabolic Diseases; Metabolism; Metals; Methods; Modeling; NCI Scholars Program; Nature; Nerve Degeneration; Nervous System Physiology; Organism; Pathogenicity; Pathologic; Pathology; Phenotype; Photons; Physics; Physiological; Physiology; Play; Population; Positioning Attribute; Preparation; Process; Proteins; Quantitative Evaluations; Regulation; Reproduction; Research; Research Personnel; Resource Allocation; Resources; Roentgen Rays; Role; Sampling; Scanning; Science; Slice; Source; Standardization; Technology; Tissues; Training; Transition Elements; United States National Institutes of Health; Universities; Work; Zinc; applied biomedical research; community engagement; design; detection method; faculty research; fundamental research; image registration; imaging modality; indexing; meetings; multidisciplinary; new technology; pathogen; photoacoustic imaging; programs; recruit; single cell technology; technology research and development; training opportunity; visiting scholar

PROJECT SUMMARY – OVERALL Inorganic chemistry plays myriad, evolutionarily-conserved roles in physiology and pathology. Cells must accumulate several metals, such as zinc and iron, to millimolar levels in order to survive. They can deploy fluctuations in metal content to control processes as varied as the mammalian cell cycle, pathogen infection and neurological function. The critical regulatory role of metals is emphasized by the observation that one-third of all protein-encoding genes in the human genome encode metal-dependent proteins. There is an increasing appreciation in the NIH research community that intracellular content and subcellular location of each element provides an inorganic signature that serves as a quantitative phenotype. These realizations are driving the demand for new technologies for quantitative evaluation of inorganic signatures in cells and tissues. Such methods are essential to understanding the regulation of physiological and pathogenic processes and developmental decisions. The proposed Resource for Elemental Imaging for Life Sciences (QE-Map) will develop and integrate emerging technologies to create transformative approaches to the compelling biological question concerning inorganic chemistry in health and disease. The technologies to be developed comprise a suite of three imaging and detection methods that will allow investigators to quantitatively map the distribution of dozens of elements in samples ranging from cell extracts to fixed cells to tissue slices. The complementary and integrative nature of these methods is critical to enabling investigators to examine fluxes in intracellular ion content and localization, and to link these fluxes to changes in distribution within tissues and in living animals. A multi-disciplinary team, located at Northwestern University and Argonne National Laboratories, will address current limitations of LA-ICP-MS and SXFM technologies and will launch the development of photoacoustic methods and probes to enable studies at the tissue level. We will develop workflows and software that allows co-registration of images and standardization of quantitative data that will maximize the impact and accelerate application to a broad range of biomedical research. A portfolio of twelve DBPs was selected for their capacity to enable iterative development of new methods, and address high impact research questions in the field of “inorganic physiology.” The DBPs focus on 4 themes: (a) metal regulation in brain function and pathology; (b) metal modulation of host-pathogen interactions; (c) metal fluxes controlling reproduction and development; and (d) metal imbalances in metabolic pathology. A Community Engagement program will foster training of new technology users and dissemination of the technologies to the scientific community. The integration and coordination of Resource projects and activities will be enabled by the Administrative Core, co-directed by Drs. Thomas O’Halloran and Chris Jacobsen, and supported by an External Advisory Committee and an Executive Committee.

项目总结--总体 无机化学在生理学和病理学中扮演着无数进化保守的角色。单元格必须 为了生存，要积累几种金属，如锌和铁，达到毫摩尔水平。他们可以部署 金属含量的波动控制过程，如哺乳动物细胞周期、病原体感染等 和神经功能。金属的关键调节作用是通过观察到三分之一的 在人类基因组中的所有编码蛋白质的基因中，都编码金属依赖的蛋白质。有越来越多的人 NIH研究界对每种元素的细胞内含量和亚细胞位置的赞赏 提供了一种作为定量表型的无机信号。这些认识正在推动 对细胞和组织中无机特征定量评估的新技术的需求。是这样的 方法对于理解生理和致病过程的调节和 发展决策。拟议的生命科学元素成像资源(QE-Map)将 开发和集成新兴技术，为引人注目的生物多样性创造变革性的方法 关于健康和疾病中的无机化学的问题。 将开发的技术包括一套三种成像和检测方法，将使 研究人员定量绘制了从细胞提取液到样品中数十种元素的分布 将细胞固定在组织切片上。这些方法的互补性和整体性对于实现 研究人员检查细胞内离子含量和定位的通量，并将这些通量与变化联系起来 在组织内和活着的动物体内分布。位于西北大学的多学科团队 和阿贡国家实验室，将解决目前LA-ICPMS和SXFM技术的局限性，并 将启动光声方法和探头的开发，以便能够在组织层面进行研究。我们会 开发允许图像联合配准和量化数据标准化的工作流程和软件 这将使影响最大化，并加快在广泛的生物医学研究中的应用。 选择了12个DBP的组合，因为它们具有迭代开发新方法的能力， 并提出了“无机生理学”领域的高影响力研究问题。DBP重点关注4个主题： (A)大脑功能和病理中的金属调控；(B)宿主-病原体相互作用的金属调控；(C) 控制生殖和发育的金属通量；和(D)代谢病理学中的金属失衡。 社区参与计划将促进对新技术用户的培训和传播 向科学界提供技术。资源项目和活动的整合和协调 将由Thomas O‘Halloran博士和Chris Jacobsen博士共同执导的管理核心支持，以及 由一个外部咨询委员会和一个执行委员会提供支助。