Center for Genomically Engineered Organs

 描述(申请人提供)：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来开发复杂组织的改进模型。这些组织将在实验室由重新编程或转基因的干细胞或其他细胞生产，将包含多种细胞类型和血管，并将被设计并与自然(健康或疾病)组织进行严格比较，以便它们在分子水平和整个组织结构上都非常匹配。这些模型组织有可能极大地加快生物医学的进步，因为它为研究人员提供了一种方法，可以在他们的实验室中快速、廉价地对正常和疾病生物学理论进行初步测试，然后再在动物或人类身上进行代价高昂、可能具有侵入性的实验。CGEOS研究分为三个目标。在目标1中，CGEO将开发在分子水平上对组织进行现场综合分析的方法，方法是获取每个组织单个细胞中的高通量RNA表达、蛋白质表达和表观基因组数据，以及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自然对应细胞进行比较，不仅系统地评估它们相应的细胞类型分子轮廓匹配的程度，而且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自然组织中的自然细胞之间的匹配。CGEO将应用这些技术来建立对神经生物学和造血重要的组织模型，最后，在目标3中，还将它们应用于小鼠的体外培养胚胎和生殖系组织，这可能揭示使所有组织的模型能够在实验室产生的途径。CGEO是由波士顿地区的六个实验室合作的，它们在先进的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拥有综合专业知识。CGEO团队由乔治·丘奇(首席研究员)、大卫·辛克莱和吴朝廷教授(均来自哈佛医学院)、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(哈佛大学威斯研究所)组成。

 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).