Resource for Development of Biomedical Mass Spectrometry

描述(由申请人提供)：国家加速器质谱学资源(AMS)成立于1999年，旨在使生物医学研究人员在探索生物学基本问题的同时，准确地量化极低水平的放射性同位素。在这次更新中，我们将通过开发在单细胞和小细胞组水平上研究生化途径和细胞过程的方法来扩展我们现有的能力，这将使我们的合作者能够研究酵母中老化的影响。该资源还将开发量化内源过程的方法，例如高等生物体中的蛋白质和DNA氧化。这将促进从动脉粥样硬化到神经退行性疾病再到癌症的炎症性疾病的研究。为了进一步实现这些目标，我们将开发一种样品呈现技术，该技术将能够分析比目前可以处理的小得多的样品，以及在这些样品中生物分子的形态形成技术。在整个赠款期限内，我们将继续向研究界提供资源，包括向熟悉AMS的调查人员提供服务，对调查人员进行技术培训，以及传播资源。为达致这些目标，我们的具体目标是： 1)制定分离仪器洗脱液的在线燃烧方案，并将产品耦合到气体接受离子源，以提高AMS的灵敏度。 2.)通过量化统一同位素标记系统的分离中的同位素含量，或通过量化特定大分子的修饰或作用的衍生生物标记物，增加AMS测量的价值和信息含量。 3.)使用多种同位素示踪剂对生物系统中的效应物和效应物进行定量 在采样的材料中。我们将通过开发强大的和更高的吞吐量来实现这一目标 通过利用加速器质谱学中心(CAMS)的其他资助的同位素测量，来处理~3H样品的制备过程。 4.)为协作和服务用户提供高吞吐量和精确量化。

DESCRIPTION (provided by applicant): The National Resource for Accelerator Mass Spectrometry (AMS) was established in 1999 to enable biomedical researchers to accurately quantify very low levels of radioisotopes while exploring fundamental issues in biology. In this renewal, we will expand our present capabilities by developing methods to study biochemical pathways and cellular processes at the level of the single cell and small groups of cells, which will allow our collaborators to study the effect of aging in yeast. The Resource will also develop methods to quantify endogenous processes, such as protein and DNA oxidation in higher organisms. This will facilitate the study of inflammatory diseases ranging from atherosclerosis to neurodegenerative disorders to cancer. To further these goals, we will develop a sample presentation technology that will enable the analysis of much smaller samples than can be currently processed, as well as techniques for speciation of biomolecules in such samples. Throughout the tenure of the grant we will continue to provide a resource to the research community that will include service to investigators familiar with AMS, training of investigators in the technology and dissemination of the Resource. Towards these goals, our specific aims are to: 1.) Develop protocols for the online combustion of eluents from separatory instruments and couple the products to a gas accepting ion source to increase the sensitivity of AMS. 2.) Increase the value and information content of AMS measurements by quantitating isotope content in isolates of uniformly isotope-labeled systems or by quantitating derivatized biomarkers of modification or function on specific macromolecules. 3.) Provide quantitation of effector and effect in biological systems using multiple isotopic tracers within sampled materials. We will achieve this by developing a robust and higher throughput process for 3H sample preparation and by leveraging against other funded isotope measurements at the Center for Accelerator Mass Spectrometry (CAMS). 4.) Provide high throughput and precise quantitation for collaborative and service users.