Supplement for Resource for Quantitative Elemental Mapping for the Life Sciences

生命科学定量元素图资源补充

• 批准号: 10586510
• 负责人: Chris Johnson Jacobsen
• 金额: $ 10万
• 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/10586510
• 关键词: Address; Advisory Committees; Animals; Automobile Driving; Biological; Biological Sciences; Biomedical Research; Brain; Cell Cycle; Cell Extracts; Cells; Communities; Computer software; Data; Development; Disease; Elements; Emerging Technologies; Fostering; Genes; Health; Human Genome; Image; Inductively Coupled Plasma Mass Spectrometry; Infection; Inorganic Chemistry; Ions; Iron; Laboratories; Link; Location; Mammalian Cell; Maps; Metabolic; Metals; Methods; Nature; Nervous System Physiology; Pathogenicity; Pathology; Phenotype; Physiological; Physiology; Play; Process; Proteins; Quantitative Evaluations; Regulation; Reproduction; Research; Research Personnel; Resources; Role; Sampling; Slice; Standardization; Technology; Tissues; Training; United States National Institutes of Health; Universities; Zinc; community engagement; detection method; image registration; imaging modality; multidisciplinary; new technology; pathogen; programs

PROJECT SUMMARY Inorganic chemistry plays myriad, evolutionarily conserved roles in physiology and pathology. Cells must accumulate several metals, such as zinc and iron, to millimolar levels 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 无机化学在生理学和病理学中扮演着无数的、进化上保守的角色。细胞必须 积累几种金属，如锌和铁，达到毫摩尔水平才能生存。他们可以利用波动， 金属含量来控制哺乳动物细胞周期、病原体感染和神经系统等各种过程 功能金属的关键调节作用是通过观察强调的，三分之一的蛋白质- 人类基因组中的编码基因编码金属依赖性蛋白质。人们越来越欣赏 NIH研究团体认为，每个元件细胞内含量和亚细胞位置提供了一个 作为定量表型的无机标记。这些认识正在推动对新产品的需求， 用于定量评估细胞和组织中无机特征的技术。这些方法是必不可少的 了解生理和致病过程和发育决定的调节。的 拟议的生命科学元素成像资源（QE地图）将开发和整合新兴的 技术，以创造变革性的方法来解决有关无机 健康与疾病的化学 待开发的技术包括一套三种成像和检测方法， 研究人员定量绘制了几十种元素在样品中的分布， 将细胞固定在组织切片上。这些方法的互补性和综合性对于促进 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 在组织内和活体动物中的分布。一个多学科的团队，位于西北大学， 阿贡国家实验室将解决LA-ICP-MS和SXFM技术目前的局限性， 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 开发工作流程和软件，以实现图像配准和定量数据标准化 这将最大限度地扩大影响，并加速应用于广泛的生物医学研究。 12个消毒副产品的组合被选中，因为它们有能力实现新方法的迭代开发， 解决“无机生理学”领域的高影响力研究问题。DBPs侧重于4个主题： 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;（c）金属 控制生殖和发育的通量;以及（d）代谢病理学中的金属不平衡。 社区参与计划将促进对新技术用户的培训， 技术到科学界。资源项目和活动的整合和协调 将由托马斯奥哈洛伦博士和克里斯雅各布森博士共同指导的行政核心启用， 由外部咨询委员会和执行委员会提供支持。