Center for Genomically Engineered Organs

基因工程器官中心(CGEO)将结合尖端基因组学、基因组编辑 技术和组织工程方法，以开发复杂组织的改进模型。这些组织 将在实验室从重新编程或转基因的干细胞或其他细胞中生产，将包含 多种细胞类型和血管构筑，并将被设计并严格与自然(健康或 患病的)组织，使它们在分子水平和整个组织结构上紧密匹配。这些 通过为研究人员提供一种方法，模型组织有可能极大地加快生物医学进展 快速、廉价地对正常生物学和疾病生物学的理论进行初步测试 在他们不得不在动物或人类身上进行昂贵的、可能具有侵入性的实验之前，他们可以在实验室进行研究。 CGEOS研究分为三个目标。在目标1中，CGEO将开发方法来全面 通过获得高通量的RNA表达，蛋白质表达， 和表观基因组数据一起存储在每个组织的单个细胞中，以及这些数据的位置 这些细胞中的分子。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其相应的自然对应细胞进行比较，并评估 不仅系统地比较它们对应的细胞类型分子图谱匹配的程度，而且还比较 它们的整体单元架构和关系。这些算法还将指定基因组编辑和 工程学可以用来改善模型组织中的工程细胞与 天然组织的天然细胞。CGEO将应用这些技术来建立对 神经生物学和造血学，最后，在目标3中，也将它们应用于体外培养的胚胎和生殖细胞 在小鼠体内克隆组织，这有可能揭示使所有组织的模型能够 在实验室里产生的。CGEO是由波士顿地区的六个实验室与联合 在高级基因组和蛋白质组技术、基因组工程、发育系统、干细胞 细胞技术、表观遗传学、超分辨率显微镜和组织工程。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(均来自哈佛大学) 医学院)、埃德·博伊登(麻省理工学院)、乔治·戴利(儿童医院)和詹妮弗·刘易斯(威斯研究所 哈佛大学)。

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).