Biological Responses Core

暴露评估核心 7.1目标 正如整个申请中所指出的，UM NIEHS中心的总体使命是使用新颖的多学科方法促进转化研究，以更好地了解环境暴露对选定成人疾病的影响，通过涉及生命脆弱阶段的表观遗传修饰的机制。暴露评估核心通过促进暴露评估活动的设计、实施和分析来支持这一使命，其总体目标是确保暴露评估和生成的分析数据在科学上是合理的，质量得到保证，并反映最先进的知识和专业知识。请注意，斜体文字是用来标记整个显着的更新 和修订，包括评论摘录和我们的相关回应。 核心由四个实验室和一个建模组组成，即：1。有机化学实验室; 2.痕量金属实验室;（3）环境和分子微生物学实验室;（4）营养评估实验室;和（5）暴露建模和翻译。这些组件支持广泛的合作研究，包括暴露于金属，有机物，颗粒和营养物质。另外我们 将提供与暴露指标相关的研究设计的转介、协调和质量保证（QA）服务和咨询;协助采样、处理、分析和储存样本;为支持实验室提供转介服务，以分析核心本身未测量的分析物;数据解释;以及暴露建模。总的来说，核心将协调现有的设施和人员， 提高效率，并扩大能力，以实现中心的战略目标的活动和优先事项。 虽然我们认识到研究饮食对疾病的影响与NIEHS的使命不一致，但营养状况和营养摄入量可以大大改变对环境毒物的敏感性。 这种相互作用也与中心几位成员的研究有关：S.K. Park关于饮食抗氧化剂作为空气污染对心血管疾病影响的调节剂的工作（例如，Park等人，2009）; H. Hu的NIEHS超级基金项目（2000-2006，P01 ES 05947）“妊娠期膳食补充剂抑制骨吸收和动员铅进入血浆的对照试验”;和J.R. Pilsner的NIEHS支持了关于叶酸（影响整体DNA甲基化的甲基供体）对砷对基因组DNA甲基化的影响的研究（Pilsner等人，2007年）。该领域的核心联合领导人K。Peterson是一位经验丰富的营养科学家，他研究了营养素-毒物的相互作用（Hernana-Avila等人，2003; Arora等人，2008; Ettinger等人，2009），以及对身体生长和发育的影响（Gonzalez-Gossio et al.，1997; Gomaa等人，2002; Peterson等人，2004年）。 生物反应核心 7.2.1目标 如在整个申请中所指出的，密歇根大学NIEHS中心的总体使命是使用新颖的多学科方法来促进新的转化研究，以更好地理解环境暴露通过涉及生命脆弱阶段期间的表观遗传修饰的机制对选定疾病过程的影响。生物反应核心的总体目标是提供 协助设计和实施与UM NIEHS中心相关的研究，这些研究使用新鲜收集或存档的生物样本来研究表观基因组或基因组的变化，这些变化反过来可能导致基因表达或功能的变化并影响疾病表型。核心设施作为一个管道，通过生物医学研究核心，以及其他大学资源， 该核心支持三个领域的咨询服务：表观遗传学、突变检测和生物建模。请注意，斜体文本用于标记显著的更新和修订，包括 批评和我们的相关回应。 我们很感激以前的评审员对我们最初提出的生物反应核心及其在中心内的整合非常热情，“结合起来，这些核心将为中心范围内的研究提供多学科的整体支持，其总和大于部分。 这些核心代表了该提案的明显优势。领导能力被形容为“优秀”和“一流”。“我们感谢有机会微调我们的建议，并回应一些有益的批评。 这些核心设施和咨询服务支持广泛的昂贵技术和高度专业化的服务，这些服务在机构内而不是在单个实验室内得到更好的服务。这一组织结构极大地提高了效率和技术专长。拟议中的密歇根大学NIEHS中心（UM NIEHS中心）已经开发了一个广泛而令人印象深刻的 通过利用现有核心的优势，并投资开发新的服务和设备，为新的中心成员提供一系列服务。

Exposure Assessment Core 7.1.1 Goals As noted throughout the application, the overall mission of the UM NIEHS Center is to promote translational research using novel multi-disciplinary approaches to better understand the impact of environmental exposures on selected adult diseases through mechanisms involving epigenetic modifications during vulnerable stages of life. The Exposure Assessment Core supports this mission by facilitating the design, implementation and analysis of exposure assessment activity, with the overall goal of ensuring that exposure assessments and analytical data generated are scientifically sound, guality assured and reflect state -of-the-art knowledge and expertise. Please note that italicized text is used throughout to mark notable updates and revislon(s), including excerpts of critiques and our associated responses. The Core consists of four laboratories and a modeling group, namely: 1. Organic Chemistry Laboratory; 2. Trace Metals Laboratory; (3) Environmental & Molecular Microbiology Laboratory; (4) Nutrition Assessment Laboratory; and (5) Exposure Modeling and Translation. These components support a broad range of collaborative research that includes exposures to metals, organics, particles, and nutrients. Additionally, we will provide referral, coordination and quality assurance (QA) services and consultations regarding study design related to exposure indicators; assistance with sampling, processing, analysis and storage of samples; referral services to supporting laboratories for analytes not measured by the Core itself; data interpretation; and exposure modeling. Overall, the Core will coordinate existing facilities and personnel, promote efficiencies, and expand capabilities to realize the activities and priorities ofthe Center's strategic goals. While we recognize that research examining the impacts of diet on disease is not consistent with NIEHS' mission, nutritional status and nutrient intake can substantially modify susceptibility to environmental toxicants. Such interactions also are relevant to the research of several Center members: S.K. Park's work on dietary anti-oxidants as a modifier of air pollution impacts on cardiovascular disease (e.g.. Park et al., 2009); H. Hu's NIEHS Superfund Project (2000-2006, P01ES05947) "Controlled Trial in Pregnancy of Dietary Supplements for the Suppression of Bone Resorption and Mobilization of Lead into Plasma"; and J.R. Pilsner's NIEHSsupported research on folate, a methyl-donor affecting global DNA methylation, on arsenic's impact of genomic DNA methylation (Pilsner et al., 2007). The Core Co-Leader in this area, K. Peterson, is an experienced nutrition scientist who has examined nutrient-toxicant interactions (Hernandez-Avila et al., 2003; Arora et al., 2008; Ettinger et al., 2009), and effects on physical growth and development (Gonzalez-Gossio et al., 1997; Gomaa et al., 2002; Peterson et al., 2004). Biological Responses Core 7.2.1 Objectives As noted throughout the application, the overall mission of the University of Michigan NIEHS Center is to promote new translational research using novel multi-disciplinary approaches to better understand the impact of environmental exposures on selected disease processes through mechanisms involving epigenetic modifications during vulnerable stages of life. The overall goal ofthe Biological Responses Core is to provide assistance in the design and implementation of studies associated with the UM NIEHS Center that use freshly collected or archived biological samples to investigate changes to the epigenome or genome that, in turn, are likely to result in changes in gene expression or function and influence disease phenotypes. The Core facility serves as a conduit to other University resources through the Biomedical Research Cores, as well as the analysis of biomarkers of oxidation / oxidative stress, inflammation, cytokines, DNA adducts, etc. The Core supports consultative services in three areas: Epigenetics, Mutation Detection, and Biologic Modeling. Please note that Italicized text Is used throughout to mark notable updates and revision(s), including excerpts of critiques and our associated responses. We are grateful that the previous reviewers were highly enthusiastic about our original proposal for the Biological Responses Core and Its integration within the Center, "Combined, these cores will provide multidisciplinary, holistic support for Center-wide research In a fashion where their sum is greater than the parts. These cores represent a clear strength ofthe proposal." Leadership was described as "excellent" and "first rate." We appreciate the opportunity to fine-tune our proposal and respond to several helpful critiques. These Core facilities and consultative services support a broad range of expensive technology and highly specialized services that are better served institutionally rather than within individual laboratories. Profound gains in efficiency and technical expertise are harnessed with this organizational structure. The proposed University of Michigan NIEHS Center (UM NIEHS Center) has already developed an extensive and impressive array of services for new center members by taking advantage ofthe strength of existing Cores and investing in the development of new services and equipment.