Developing Biomedical Projects Portfolio

开发生物医学项目组合

• 批准号: 10197972
• 负责人: THOMAS V O'HALLORAN
• 金额: $ 3.04万
• 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/10197972
• 关键词: Address; Adoption; Advisory Committees; Affect; Anatomy; Automobile Driving; Base Pairing; Basic Science; Beds; Biological; Biological Process; Biological Sciences; Biology; Biomedical Research; Brain; Cell Cycle; Cell Extracts; Cell physiology; Cells; Cellular biology; Chemicals; Clinical Research; Collaborations; Communication; Communities; Consultations; Copper; Development; Dimensions; Disease; Disease Progression; Elements; Emerging Technologies; Enzymes; Evaluation; Foundations; Funding; Genes; Genome; Goals; Health; Human; Human Genome; Human Resources; IT collaborator; Image; Infection; Inorganic Chemistry; Institutes; Ions; Iron; Leadership; Location; Mammalian Cell; Manganese; Maps; Metabolic; Metals; Methods; Molecular; Nervous System Physiology; Onset of illness; Pathogenesis; Pathogenicity; Pathologic; Pathology; Periodicity; Phenotype; Physiological; Physiological Processes; Physiology; Play; Population; Principal Investigator; Process; Proteins; Quantitative Evaluations; Regulation; Reporter; Reproducibility; Reproduction; Research; Research Personnel; Resources; Role; Sampling; Slice; Stimulus; Technology; Teleconferences; Testing; Tissues; Transition Elements; United States National Institutes of Health; Update; Variant; Work; Zinc; base; cofactor; cohort; detection method; imaging modality; meetings; new technology; pathogen; programs; quantitative imaging; recruit; response; success; symposium; technology development

PROJECT SUMMARY – DRIVING BIOLOGICAL PROBLEMS 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 will address two grand challenges. The first is to understand how metals act within single cells to affect cell function. The second is a matter of scale: how can we efficiently analyze millions of samples to search for correlative markers of health and disease in the human population? 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. Neither of these challenges can be addressed with current technology. 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. 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 four 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. The External Advisory Committee will oversee the turnover of DBP projects to maintain a portfolio is broad in scope and responsive to the needs of the national research community while advancing and stimulating QE-Map technology development. The DBP Program Leader, Tom O’Halloran, will deploy multiple strategies establish and strengthen collaborative relationships between the DBP investigators and the technology development teams; including kick-off meetings, collaboration apps, and all-Resource meetings.

项目摘要——解决生物问题 无机化学在生理学和病理学中发挥着无数的、进化上保守的作用。细胞必须 为了生存，积累了几种金属，例如锌和铁，达到毫摩尔水平。他们可以部署 金属含量的波动来控制哺乳动物细胞周期、病原体感染等各种过程 和神经功能。观察结果强调了金属的关键监管作用： 人类基因组中所有蛋白质编码基因中有三分之一编码金属依赖性蛋白质。有一个 NIH 研究界越来越认识到细胞内内容和亚细胞位置 每个元素都提供了作为定量表型的无机特征。这些实现是 推动对细胞中无机特征定量评估新技术的需求 组织。这些方法对于理解生理和致病的调节至关重要。 流程和发展决策。拟议的资源将解决两大挑战。这 首先是了解金属如何在单个细胞内发挥作用来影响细胞功能。第二个是规模问题： 我们如何有效地分析数百万个样本，以寻找健康和疾病的相关标记 人口？ 拟议的生命科学元素成像资源（QE-Map）将开发和集成 新兴技术为解决紧迫的生物学问题创造变革性方法 健康和疾病中的无机化学。这些挑战都无法通过当前的解决方案来解决 技术。待开发的技术包括一套三种成像和检测方法， 将使研究人员能够定量绘制样品中数十种元素的分布图，范围从 细胞提取物到固定细胞到组织切片。选择十二个 DBP 的投资组合是因为他们有能力实现 新方法的迭代开发，并解决“无机”领域的高影响力研究问题 生理。” DBP 重点关注四个主题：(a) 脑功能和病理学中的金属调节； (b) 金属 调节宿主-病原体相互作用； (c) 控制繁殖和发育的金属通量；和（四） 代谢病理学中的金属失衡。外部咨询委员会将监督 DBP 的营业额 维持投资组合的项目范围广泛，并能满足国家研究的需求 社区，同时推进和刺激 QE-Map 技术的发展。 DBP 项目负责人， 汤姆·奥哈洛伦 (Tom O’Halloran) 将部署多种策略，建立并加强双方的合作关系 DBP 研究人员和技术开发团队；包括启动会议、合作 应用程序和全资源会议。