Developing Biomedical Projects Portfolio

项目摘要--引发生物问题 无机化学在生理学和病理学中扮演着无数进化保守的角色。单元格必须 为了生存，要积累几种金属，如锌和铁，达到毫摩尔水平。他们可以部署 金属含量的波动控制过程，如哺乳动物细胞周期、病原体感染等 和神经功能。金属的关键调节作用是通过以下观察来强调的： 人类基因组中所有编码蛋白质的基因中，有三分之一编码金属依赖的蛋白质。有一个 NIH研究界越来越多地认识到，细胞内的含量和亚细胞的位置 每种元素都提供了一种无机信号，作为一种数量表型。这些实现是 推动对细胞和细胞中无机特征定量评估的新技术的需求 纸巾。这些方法对于理解生理和致病的调节是必不可少的。 进程和发展决策。拟议的资源将应对两个重大挑战。这个 首先是了解金属在单个细胞内是如何影响细胞功能的。第二个是规模问题： 我们如何有效地分析数以百万计的样本，以寻找健康和疾病的相关标志 人类人口？ 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，以创造变革性的方法来解决有关 无机化学在健康和疾病中的作用。这两个挑战都不能通过当前的 技术将开发的技术包括一套三种成像和检测方法，这些方法 将允许调查人员定量绘制样本中数十种元素的分布图，范围从 从细胞提取液到固定细胞到组织切片。选择了一个由12个DBP组成的投资组合，因为他们的能力可以实现 迭代开发新的方法，并解决“无机物”领域的高影响力研究问题 生理学。“DBP侧重于四个主题：(A)大脑功能和病理中的金属调节；(B)金属 寄主-病原体相互作用的调节；(C)控制繁殖和发育的金属熔剂；和(D) 代谢病理学中的金属失衡。外部咨询委员会将监督DBP的更替 保持项目组合的项目范围广泛，符合国家研究的需要。 社区，同时推动和刺激量化宽松地图技术的发展。DBP项目负责人， Tom O‘Halloran将部署多项战略，建立和加强 DBP调查员和技术开发团队；包括启动会议、协作 应用程序和全资源会议。

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.