Biological Responses Core

暴露评估核心 7.1.1目标 正如在整个申请过程中指出的那样，密歇根大学NIEHS中心的总体使命是利用新颖的多学科方法促进转化性研究，通过涉及脆弱生命阶段表观遗传修改的机制，更好地了解环境暴露对选定成人疾病的影响。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，其总体目标是确保所产生的暴露评估和分析数据科学可靠、质量有保证，并反映最先进的知识和专门知识。请注意，始终使用斜体文本来标记显著的更新 和审校(S)，包括批评摘录和我们的相关回应。 核心由四个实验室和一个模拟小组组成，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；以及(5)暴露模拟和翻译。这些成分支持广泛的合作研究，包括接触金属、有机物、颗粒和营养物质。此外，我们 将就与暴露指标有关的研究设计提供转介、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；为非核心本身测量的分析物向支助实验室提供转介服务；数据解释；以及暴露建模。总体而言，核心将协调现有设施和人员，促进 提高效率，扩大能力，以实现中心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在很大程度上改变对环境毒物的敏感性。 这种相互作用也与几个中心成员的研究有关：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修饰剂的工作(例如。这些研究包括：H.Hu的NIEHS超级基金项目(2000-2006年，P01ES05947)，“妊娠期应用膳食补充剂抑制骨吸收和动员铅进入血浆的对照试验”；J.R.Pilsner的NIEHS支持的关于叶酸的研究(叶酸是一种影响全球DNA甲基化的甲基供体，对基因组DNA甲基化的影响)(Pilsner等人，2007年)。该领域的核心共同领导者K.Peterson是一位经验丰富的营养学家，他研究了营养毒物之间的相互作用(Hernandez-Avila等人，2003年；Arora等人，2008年；Ettinger等人，2009年)以及对身体生长和发育的影响(Gonzalez-Gasio等人，1997年；Gomaa等人，2002年；Peterson等人，2004年)。 生物反应核心 7.2.1目标 正如在整个申请过程中所指出的，密歇根大学NIEHS中心的总体使命是利用新颖的多学科方法促进新的转化研究，以通过涉及生命脆弱阶段表观遗传修改的机制更好地了解环境暴露对选定疾病过程的影响。生物反应核心的总体目标是提供 协助设计和实施与密歇根大学NIEHS中心相关的研究，这些研究使用新收集或存档的生物样本来调查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。核心设施是通过生物医学研究中心以及 分析氧化/氧化应激、炎症、细胞因子、DNA加合物等生物标志物。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，始终使用斜体文本来标记显著的更新和修订(S)，包括 批评和我们相关的回应。 我们感谢之前的评审者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，“综合起来，这些核心将以一种总和大于部分的方式为整个中心的研究提供多学科的整体支持。 这些核心代表了提案的明显优势。“领导力被描述为”优秀“和”一流“。我们感谢有机会对我们的提案进行微调，并对几个有用的批评做出回应。 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，这些服务更适合在机构内提供，而不是在个别实验室内提供。这一组织结构充分利用了效率和技术专长方面的巨大进步。拟议中的密歇根大学NIEHS中心(UM NIEHS Center)已经开发出了广泛和令人印象深刻的 通过利用现有核心的优势并投资于新服务和设备的开发，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.