Resource for Quantitative Elemental Mapping for the Life Sciences

生命科学定量元素图谱资源

• 批准号: 10197965
• 负责人: Chris Johnson Jacobsen
• 金额: $ 98.63万
• 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/10197965
• 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.

项目概要——总体 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。三分之一的观察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都编码金属依赖性蛋白质。有越来越多的 NIH 研究界对每个元素的细胞内含量和亚细胞位置的认识 提供充当定量表型的无机特征。这些认识正在推动 对定量评估细胞和组织中无机特征的新技术的需求。这样的 方法对于理解生理和致病过程的调节至关重要 发展决策。拟议的生命科学元素成像资源（QE-Map）将 开发和整合新兴技术，为引人注目的生物技术创造变革性方法 关于健康和疾病中的无机化学的问题。 待开发的技术包括一套三种成像和检测方法，这些方法将允许 研究人员定量绘制细胞提取物等样品中数十种元素的分布图 将细胞固定到组织切片上。这些方法的互补性和综合性对于实现 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 分布在组织内和活体动物中。位于西北大学的多学科团队 和阿贡国家实验室，将解决 LA-ICP-MS 和 SXFM 技术的当前局限性， 将启动光声方法和探针的开发，以实现组织水平的研究。我们将 开发允许图像共同配准和定量数据标准化的工作流程和软件 这将最大限度地发挥影响并加速其在广泛的生物医学研究中的应用。 十二个 DBP 的组合因其能够迭代开发新方法的能力而被选中， 并解决“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) 脑功能和病理学中的金属调节； (b) 宿主-病原体相互作用的金属调节； (三) 控制繁殖和发育的金属通量； (d) 代谢病理学中的金属失衡。 社区参与计划将促进新技术用户的培训和新技术的传播 向科学界提供技术。资源项目和活动的整合和协调 将由行政核心启用，由博士共同领导。托马斯·奥哈洛伦和克里斯·雅各布森，以及 由外部咨询委员会和执行委员会支持。