Developing Biomedical Projects Portfolio

项目总结-驱动生物学问题 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 为了生存，它们积累了几种金属，如锌和铁，达到毫摩尔的水平。他们可以部署 金属含量的波动，以控制各种过程，如哺乳动物细胞周期，病原体感染 和神经功能。金属的关键调节作用是通过观察强调的，即一个- 人类基因组中所有蛋白质编码基因的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， 每种元素都提供了一种无机标记，作为定量表型。这些认识是 推动对用于定量评估细胞中无机特征的新技术的需求， 组织中这些方法对于理解生理和致病性的调节是必不可少的 过程和发展决策。拟议资源将应对两大挑战。的 首先是了解金属如何在单细胞内作用以影响细胞功能。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志物， 人类人口？ 拟议的生命科学元素成像资源（QE地图）将开发和整合 新兴技术，以创造变革性的方法来解决紧迫的生物问题， 健康与疾病中的无机化学这两个挑战都不能用当前的 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， 将细胞提取物固定到组织切片上。选择了十二个DBP组合，因为它们能够 迭代开发新方法，并解决"无机"领域的高影响力研究问题 生理学" DBPs集中在四个主题：（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）控制生殖和发育的金属通量;和（d） 代谢病理学中的金属失衡。外聘咨询委员会将监督开发计划署的周转情况， 项目，以保持投资组合是广泛的范围和响应的需要，国家的研究 社区，同时推进和刺激QE-Map技术的发展。DBP项目负责人， Tom O'Halloran将部署多种战略，建立和加强 DBP调查人员和技术开发团队;包括启动会议、合作 应用程序和所有资源会议。

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.