Core C: Genomics and High Throughput Screening Core

该核心提供尖端工具，使研究人员能够监测在正常造血期间或在与骨髓衰竭(BMF)、非恶性骨髓增生异常综合征或红细胞/巨核细胞生成缺陷相关的病理状态下发生的细胞和分子变化，解决了总体描述中详细说明的这一应用的三个重点。显然有必要提供服务，以快速、高通量的方式识别和分析影响造血细胞对各种谱系的承诺的药物，并开发用于基质/利基环境研究的微型系统。戴蒙德博士是宾夕法尼亚大学(UPenn)PCMD的主任，他于2005年建立了该中心作为核心设施(见Biosketch)。戴蒙德博士在内皮生物学、血液生物学和血液系统生物学方面拥有20年的丰富经验。他已经在与庞茨博士、弗伦奇博士和加杜博士合作，研究成熟巨核细胞对血小板生成的利基效应。他将担任亚核C-1的总董事和董事。鲍德温博士将负责分析细胞在造血过程中的RNA和DNA变化。他在微阵列分析方面拥有11年的工业和学术经验，在美国国立卫生研究院神经科学微阵列联盟顾问小组任职，担任生物分子资源设施协会微阵列研究小组的联合主席，并定期与国家层面的核心主管互动(见biosketch)。鲍德温博士于2001年创立了宾夕法尼亚微阵列设施，2005年被任命为分子诊断和基因分型设施的主任，并将这两个实验室合并为分子图谱设施。他曾与Weiss博士、Blobel博士、Carroll博士、Diamond博士、Discher博士、Gewirtz博士、琼博士和Pear博士一起进行过与P30直接相关的基因组图谱项目。 我们结合了戴蒙德博士和鲍德温博士运行的两个宾夕法尼亚大学核心的组件，为P30开发了一个单一核心，整合了我们校园内的最先进资源，将联合我们分析正常、病理和操纵的造血细胞的能力。亚核C-1为影响造血细胞生物学各个方面的化合物提供了高通量的微型筛选，包括谱系承诺(来自胚胎干细胞或更多分化的祖细胞)、存活、增殖或成熟为成熟血细胞。亚核C-2将分析这些细胞中的RNA表达谱和表观遗传DNA标记发生的变化，无论是从头开始还是使用核心E进行修改后。我们相信，这两个亚核反映了一个共同的主题，即使用复杂的方法快速分析细胞和细胞变化，并在快速变化的设备和技术上进行大量投资。CORE C致力于为P30调查人员带来最新和最具创新性的技术，同时提供校园范围的标准化服务，以支持具有互补兴趣和专业知识的不同调查人员的合作努力。我们的目标是以极具竞争力的价格提供重要的劳动密集型服务和指导，这在一定程度上得到了利用率和宾夕法尼亚大学财政支持的支持。

This Core provides cutting edge tools that allow investigators to monitor cellular and molecular changes that occur during normal hematopoiesis or in pathological states associated with bone marrow failure (BMF), nonmalignant myelodysplastic syndromes or defects in erythropoiesis/megakaryopoiesis, addressing the three foci of this application as detailed in the OVERALL DESCRIPTION. There is a clear need for services to identify and analyze in a rapid, high throughput fashion drugs that influence hematopoietic cell commitment to various lineages and to develop miniaturized systems for studies of stromal/niche environments. Dr. Diamond is the director of the University of Pennsylvania (UPENN) PCMD, which he established as a Core Facility in 2005 (see BIOSKETCH). Dr. Diamond has 20 years of experience with numerous projects in endothelial biology, blood biology, and blood systems biology. He already has been working with Drs. Poncz, French and Gadue on niche effects on thrombopoiesis from mature megakaryocytes. He will be overall Director and Director of SubCore C-1. Dr. Baldwin will direct the analysis of RNA and DNA changes in cells during hematopoiesis. He has 11 years of industrial and academic experience in microarray assays, serves on the Neuroscience Microarray Consortium Advisory Panel for the NIH, co-chairs the MicroArray Research Group of the Association of Biomolecular Resource Facilities, and interacts regularly with core directors on a national level (see BIOSKETCH). Dr. Baldwin founded the Penn Microarray Facility in 2001, was appointed Director of the Molecular Diagnosis and Genotyping Facility in 2005, and has merged the two laboratories to create the Molecular Profiling Facility. He has conducted previous genomic profiling projects with Drs. Weiss, Blobel, Carroll, Diamond, Discher, Gewirtz, June and Pear on efforts directly relevant to this P30. We have combined components of the two UPENN cores run by Drs. Diamond and Baldwin to develop a single core for this P30 to incorporate state-of-the-art resources on our campus that will unite our abilities to analyze normal, pathologic and manipulated hematopoietic cells. SubCore C-1 offers high-throughput microscale screening for compounds that affect various aspects of hematopoietic cell biology, including lineage commitment (either from embryonic stem (ES) cells or more differentiated progenitors), survival, proliferation or maturation into mature blood cells. SubCore C-2 will analyze changes that occur in the RNA expression profiles and epigenetic DNA marks in these cells either de novo or after modifications using Core E. We believe that these two SubCores reflect a common theme of rapidly analyzing cells and cellular changes using complex methodologies with significant investment in rapidly changing equipment and technologies. Core C is committed to bringing the most current and innovative technologies to the P30 investigators, while providing campus-wide standardization of services to support cooperative efforts by different investigators with complementary interests and expertise. Our goal is to provide significant labor-intensive service and guidance at very competitive pricing, supported in part by efficiency of utilization and by UPENN financial support.