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）将结合尖端基因组学、基因组编辑技术和组织工程方法来开发复杂组织的改进模型，这些组织将可以在实验室中通过重新编程或基因改造来生产。干细胞或其他细胞，将包含多种细胞类型和脉管系统，并将与自然（健康或患病）组织进行设计和严格比较，以便它们在分子水平和整体组织中紧密匹配这些模型组织有潜力极大地加快生物医学的进步，为研究人员提供一种在实验室中快速、廉价地对正常和疾病生物学理论进行初步测试的方法，然后再对动物或人类进行昂贵且具有潜在侵入性的实验。 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全面分析原位组织的方法，通过在每个目标中同时获取高通量RNA表达、蛋白质表达和表观基因组数据。在目标 2 中，CGEO 将开发并应用创新的计算技术，将模型组织中的细胞与其相应的天然分子进行比较，并系统地评估其相应算法细胞的接近程度。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。将应用这些技术来构建模型组织对神经生物学和造血作用很重要，最后，在目标 3 中，还将它们应用于体外培养的小鼠胚胎和种系组织，这有可能揭示在实验室中生成所有组织模型的途径。 CGEO 团队由波士顿地区的六个实验室合作，拥有先进基因组和蛋白质组技术、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的专业知识。教授包括 George Church（首席研究员）、David Sinclair 和 Chao-Ting Wu（均来自哈佛医学院）、Ed Boyden（麻省理工学院）、George Daley（儿童医院）和 Jennifer Lewis（哈佛大学维斯研究所）。