Core D: Research Support Core

项目摘要 研究支持核心（RSC）将提供广泛的高质量定量分析技术 平台涵盖代谢组学、表观基因组学、转录组学和蛋白质组学。RSC的领导人是迪恩博士 P.爱德华兹，先进技术核心的执行董事在英特尔。RSC的共同领导人是Nagireddy博士 Putluri也是代谢组学核心的主任，是质谱分析领域公认的领导者， 基于代谢组学分析区域服务中心有以下具体目标。AIM 1将有效支持 超级基金项目与尖端的定量多组学技术。核心技术 包括基于质谱的靶向和无偏代谢组学、无偏蛋白质组学分析 通过质谱，通过基于抗体的反相蛋白质阵列（RPPA）的靶向蛋白质组学， 基因组学平台，如全基因组测序、RNA-seq转录组学、小RNA测序 和ChIP-Seq的表观遗传学RSC支持将包括来自教师级核心主任的智力投入， 咨询和实验设计，托管先进仪器，执行最先进的分析 核心研究人员的程序以及“组学”数据集的处理和分析。RSC技术 平台将主要用于项目2、3和4，以确定多环芳烃的生物标志物和分子特征。 与早产（PTB）相关的芳烃（PAH）暴露，并定义分子 PAH及其衍生物增强慢性肺损伤作用的机制 疾病/支气管肺发育不良（BPD）和神经行为缺陷的实验模型和人类 问题研究代谢组学核心还将有助于测量和定量PAH及其 通过GC-MS分析代谢物，作为开发更灵敏和更简单分析的标准。 1和2. AIM 2将继续与项目领导和研究人员合作，开发、验证和部署 在赠款过程中采用新的方法，而目前不是标准的核心程序。这将首先 包括新型PAH衍生物和代谢物MS鉴定，以及无偏代谢组学分析， 通过RPPA、全基因组DNA对组蛋白修饰和染色质修饰酶进行表观遗传分析 甲基化和氧化还原蛋白质组学。AIM 3将培训调查人员， 设计、执行和解释RSC进行的最先进分析技术的结果。 这将通过提供教程，研讨会和一些动手的机会，原则 研究生和博士后研究生的培训。最终目标 RSC的使命是为超级基金提供最先进的技术和最优质的科学解决方案 研究者的目的是在分子机制和遗传水平上了解PAH暴露。

Project Summary The Research Support Core (RSC) will provide a wide range of high quality quantitative analytical technology platforms spanning metabolomics, epigenomics, transcriptomics, and proteomics. The RSC leader is Dr. Dean P. Edwards, Executive Director of the Advanced Technology Cores at BCM. The RSC co-leader is Dr. Nagireddy Putluri, who also serves as director of the Metabolomics Core and is a recognized leader in mass spectrometry- based metabolomics profiling. The RSC has the following specific aims. AIM 1 Will effectively support the Superfund projects with cutting edge quantitative multi-omics technologies. Established Core technologies available includes mass spectrometry-based targeted and unbiased metabolomics, unbiased proteomic profiling by mass spectrometry, targeted proteomics by antibody-based reverse phase protein array (RPPA) and genomics platforms such as whole genome sequencing, transcriptomics by RNA-seq, smallRNA sequencing and epigenetics by ChIP-Seq. RSC support will include intellectual input from faculty level Core Directors for consultation and experimental design, hosting of advanced instrumentation, executing state-of-the-art analytical procedures by research staff of Cores and processing and analysis of “omics” data sets. RSC technology platforms will be used primarily in Projects 2, 3 and 4 to identify biomarkers and molecular signatures of polycyclic aromatic hydrocarbon (PAH) exposures associated with preterm birth (PTB) and to define the molecular mechanisms underlying the potentiating effects of PAH and its derivatives on chronic lung disease/bronchopulmonary dysplasia (BPD) and neurobehavioral deficits in experimental models and in human studies. The metabolomics core will additionally be instrumental for measuring and quantification of PAH and its metabolites by GC-MS as a standard for development of more sensitive and less sophisticated assays in Projects 1 and 2. AIM 2 Will continuously work with Project leaders and investigators to develop, validate, and deploy novel methods during the course of the grant that are not currently standard Core procedures. This will initially include MS identification of novel PAH derivatives and metabolites, and unbiased metabolomics profiling, epigenetic profiling of histone modifications and chromatin modifying enzymes by RPPA, genome-wide DNA methylation by bisulfite sequencing and Redox proteomics by MS methods. AIM 3 Will train investigators in designing, executing, and interpreting results of the state-of-the-art analytical techniques conducted by the RSC. This will be accomplished by providing tutorials, workshops and some hands-on opportunities for principle investigators of the Superfund grant and their post-doctoral and graduate student trainees. The ultimate goal of the RSC is to provide cutting-edge technical and the best quality scientific solutions available for the Superfund investigators for use in their Aims of understanding PAH exposures at molecular mechanistic and genetic levels.