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.

项目摘要 - 总体 无机化学在生理和病理学中扮演着无数，进化保存的角色。必须 为了生存，将几种金属（例如锌和铁）累积到毫米水平。他们可以部署 金属含量的波动以控制与哺乳动物细胞周期一样多样的过程，病原体感染 和神经功能。三分之一的观察结果强调了金属的关键调节作用 人基因组中所有蛋白质编码基因编码金属依赖性蛋白质。越来越多 NIH研究界的欣赏每个元素的细胞内含量和亚细胞位置 提供无机签名，可作为定量表型。这些实现正在推动 对细胞和组织中无机特征进行定量评估的新技术的需求。 方法对于了解生理和致病过程的调节至关重要 发展决策。提出的用于生命科学元素成像的资源（QE-MAP）将 开发和集成的新兴技术，以创建引人入胜的生物学的变革性方法 有关健康和疾病无机化学的问题。 要开发的技术包括三种成像和检测方法的套件，该方法将允许 研究人员定量映射来自细胞提取物的样品中数十个元素的分布 将细胞固定在组织切片上。这些方法的完整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中的通量，并将这些通量与变化联系起来 在组织内部和活体动物中的分布。一个多学科的团队，位于西北大学 和Argonne National Laboratories将解决LA-ICP-MS和SXFM技术的当前局限性以及 将启动光声方法和问题的发展，以使组织水平的研究能够进行研究。我们将 开发工作流和软件，允许共同注册图像和定量数据的标准化 这将最大程度地发挥影响并加速对广泛的生物医学研究的应用。 选择了十二个DBP的投资组合，以便能够迭代开发新方法，即 并解决了“无机生理学”领域的高影响研究问题。 DBP专注于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制； （C） 金属通量控制繁殖和发育； （d）代谢病理中的金属失衡。 社区参与计划将促进对新技术用户的培训，并传播 科学界的技术。资源项目和活动的集成和协调 由DRS共同执导的管理核心将启用。托马斯·奥哈洛兰（Thomas O’Halloran）和克里斯·雅各布森（Chris Jacobsen） 得到外部咨询委员会和执行委员会的支持。