Center for Genomically Engineered Organs

基因组工程器官中心

• 批准号: 9330898
• 负责人: GEORGE M CHURCH
• 金额: $ 193.52万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-21 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9330898
• 关键词: Address; Algorithms; Animal Model; Animals; Architecture; Area; Biological; Biological Models; Biology; Biomedical Research; Blood Vessels; Boston; Cell Differentiation process; Cells; Cellular Structures; Church; Clinical Trials; Collaborations; Complement; Complex; Computational algorithm; Computer-Aided Design; DNA; Data; Development; Disease; Embryo; Embryonic Development; Engineering; Epigenetic Process; Generations; Genetic Transcription; Genome engineering; Genomics; Germ Lines; Goals; Health; Hematopoiesis; Human; In Situ; In Vitro; Individual; Institutes; Knowledge; Laboratories; Location; Methods; Microscopy; Modeling; Molecular; Molecular Profiling; Mus; Neurobiology; Normal tissue morphology; Organ; Organoids; Pathologic; Pathway interactions; Pattern; Pediatric Hospitals; Physiological; Principal Investigator; Process; Production; Property; Proteins; Proteomics; RNA; Reading; Reagent; Research; Research Personnel; Resolution; Specific qualifier value; Stem cells; Structure; System; Technology; Testing; Time; Tissue Engineering; Tissue Model; Tissues; Translating; Work; Writing; cell type; cost; design; effective therapy; embryo tissue; epigenomics; experimental study; genome editing; improved; innovation; medical schools; novel; professor; programs; protein expression; protein profiling; public health relevance; single cell proteins; stem; stem cell differentiation; stem cell technology; technology development; theories

 DESCRIPTION (provided by applicant): The Center for Genomically Engineered Organs (CGEO) will combine cutting edge genomics, genome editing technology, and tissue engineering methods to develop improved models of complex tissues. These tissues will be producible in laboratories from reprogrammed or genetically modified stem or other cells, will contain multiple cell types and vasculatures, and will be designed and rigorously compared against natural (healthy or diseased) tissues so that they match closely at both a molecular level and in overall tissue architecture. These model tissues have potential to greatly expedite biomedical progress by providing researchers a way to conduct preliminary tests of theories about normal and disease biology quickly and inexpensively in their laboratories before they have to move on to costly and potentially invasive experiments on animals or humans. CGEOs research is divided into three Aims. In Aim 1, CGEO will develop methods to comprehensively analyze tissues in situ at a molecular level, by acquiring high-throughput RNA expression, protein expression, and epigenomic data together in each of the tissue's individual cells, along with the locations of these molecules in these cells. In Aim 2, CGEO will develop and apply innovative computational algorithms that compare the cells in the model tissues against their corresponding natural counterparts and assess systematically not only how closely their corresponding cell type molecular profiles match, but also compare their overall cell architectures and relationships. These algorithms will also specify how genome editing and engineering can be used to improve the matching between the engineered cells in the model tissue and the natural cells of the native tissue. CGEO will apply these technologies to build model tissues important to neurobiology and hematopoiesis, and, finally, in Aim 3, also apply them to in vitro cultured embryos and germ line tissues in mice, which has potential to reveal pathways that will enable models of all tissues to be generated in a laboratory. CGEO is a collaboration of six laboratories in the Boston area with combined expertise in advanced genomic and proteomic technology, genome engineering, developmental systems, stem cell technology, epigenetics, super-resolution microscopy, and tissue engineering. The CGEO team comprises Professors George Church (Principal Investigator), David Sinclair, and Chao-Ting Wu (all from Harvard Medical School), Ed Boyden (MIT), George Daley (Children's Hospital), and Jennifer Lewis (Wyss Institute at Harvard).

 描述（由申请人提供）：基因组工程器官中心（CGEO）将结合联合收割机尖端基因组学、基因组编辑技术和组织工程方法，开发复杂组织的改进模型。这些组织将在实验室中由重编程或遗传修饰的干细胞或其他细胞产生，将包含多种细胞类型和血管，并且将被设计并与天然（健康或患病）组织进行严格比较，使得它们在分子水平和整体组织结构上紧密匹配。这些模型组织有可能大大加快生物医学的进展，为研究人员提供了一种方法，在他们不得不继续对动物或人类进行昂贵且可能具有侵入性的实验之前，在实验室中快速廉价地对正常和疾病生物学理论进行初步测试。CGEO的研究分为三个目标。在目标1中，CGEO将开发在分子水平上原位综合分析组织的方法，通过在每个组织的单个细胞中同时获得高通量RNA表达，蛋白质表达和表观基因组数据，沿着这些分子在这些细胞中的位置。在目标2中，CGEO将开发和应用创新的计算算法，将模型组织中的细胞与相应的天然对应物进行比较，并系统地评估它们相应的细胞类型分子谱匹配的程度，还比较它们的整体细胞结构和关系。这些算法还将指定如何使用基因组编辑和工程来改善模型组织中的工程细胞与天然组织的天然细胞之间的匹配。CGEO将应用这些技术构建对神经生物学和造血重要的模型组织，最后，在目标3中，还将其应用于体外培养的小鼠胚胎和生殖系组织，这有可能揭示能够在实验室中生成所有组织模型的途径。CGEO是波士顿地区六个实验室的合作，在先进的基因组和蛋白质组学技术，基因组工程，发育系统，干细胞技术，表观遗传学，超分辨率显微镜和组织工程方面具有综合专业知识。CGEO团队包括乔治丘奇教授（首席研究员）、大卫辛克莱教授和吴朝廷教授（均来自哈佛医学院）、艾德博伊登教授（麻省理工学院）、乔治戴利教授（儿童医院）和詹妮弗刘易斯教授（哈佛韦恩斯研究所）。