Center for Genomically Engineered Organs

基因组工程器官中心

• 批准号: 9928553
• 负责人: GEORGE M CHURCH
• 金额: $ 3.56万
• 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/9928553
• 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; single cell proteins; stem; stem cell differentiation; stem cell technology; technology development; theories

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).

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 将可在实验室中用重新编程或基因改造的干细胞或其他细胞生产，将包含 多种细胞类型和脉管系统，并将被设计并与自然（健康或 患病）组织，以便它们在分子水平和整体组织结构上紧密匹配。这些 模型组织有潜力极大地加速生物医学的进步，为研究人员提供了一种方法 快速且廉价地对正常和疾病生物学理论进行初步测试 实验室必须继续对动物或人类进行昂贵且可能具有侵入性的实验。 CGEO的研究分为三个目标。在目标 1 中，CGEO 将开发方法来全面 通过获取高通量 RNA 表达、蛋白质表达、 和表观基因组数据在每个组织的单个细胞中，以及这些细胞的位置 这些细胞中的分子。在目标 2 中，CGEO 将开发并应用创新的计算算法， 将模型组织中的细胞与其相应的天然对应物进行比较并评估 不仅系统地比较它们相应的细胞类型分子谱的匹配程度，而且还比较 他们的整体细胞架构和关系。这些算法还将指定基因组编辑和 工程可用于改善模型组织中的工程细胞与实际细胞之间的匹配性 天然组织的天然细胞。 CGEO 将应用这些技术来构建重要的组织模型 神经生物学和造血学，最后，在目标 3 中，还将它们应用于体外培养的胚胎和胚芽 小鼠体内的细胞系组织，有可能揭示使所有组织模型成为可能的途径 在实验室中生成。 CGEO 是波士顿地区六个实验室的合作项目 先进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 George Church 教授（首席研究员）、David Sinclair 和 Chao-Ting Wu（均来自哈佛大学） 医学院）、Ed Boyden（麻省理工学院）、George Daley（儿童医院）和 Jennifer Lewis（威斯研究所） 哈佛）。

项目成果

helixCAM: A platform for programmable cellular assembly in bacteria and human cells.

helixCAM：细菌和人体细胞中可编程细胞组装的平台。

• 发表时间: 2022-09-15
• 影响因子: 64.5
• 作者: Chao, George;Wannier, Timothy M;Gutierrez, Clair;Borders, Nathaniel C;Appleton, Evan;Chadha, Anjali;Lebar, Tina;Church, George M
• 通讯作者: Church, George M

Massively targeted evaluation of therapeutic CRISPR off-targets in cells.

对细胞中治疗性 CRISPR 脱靶的大规模靶向评估。

• 发表时间: 2022-07-13
• 影响因子: 16.6
• 作者: Pan, Xiaoguang;Qu, Kunli;Yuan, Hao;Xiang, Xi;Anthon, Christian;Pashkova, Liubov;Liang, Xue;Han, Peng;Corsi, Giulia I;Xu, Fengping;Liu, Ping;Zhong, Jiayan;Zhou, Yan;Ma, Tao;Jiang, Hui;Liu, Junnian;Wang, Jian;Jessen, Niels;Bolund, Lars;Ya
• 通讯作者: Ya

Enhancing CRISPR-Cas9 gRNA efficiency prediction by data integration and deep learning.

通过数据集成和深度学习增强 CRISPR-Cas9 gRNA 效率预测。

• 发表时间: 2021-05-28
• 影响因子: 16.6
• 作者: Xiang, Xi;Corsi, Giulia I;Anthon, Christian;Qu, Kunli;Pan, Xiaoguang;Liang, Xue;Han, Peng;Dong, Zhanying;Liu, Lijun;Zhong, Jiayan;Ma, Tao;Wang, Jinbao;Zhang, Xiuqing;Jiang, Hui;Xu, Fengping;Liu, Xin;Xu, Xun;Wang, Jian;Yang, Huanming;Bol
• 通讯作者: Bol

Enabling large-scale genome editing at repetitive elements by reducing DNA nicking.

通过减少 DNA 切口，实现重复元件的大规模基因组编辑。

• 发表时间: 2020
• 影响因子: 14.9
• 作者: Smith, Cory J;Castanon, Oscar;Said, Khaled;Volf, Verena;Khoshakhlagh, Parastoo;Hornick, Amanda;Ferreira, Raphael;Wu, Chun;Güell, Marc;Garg, Shilpa;Ng, Alex H M;Myllykallio, Hannu;Church, George M
• 通讯作者: Church, George M

Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels.

具有高细胞密度和嵌入式血管通道的器官特异性组织的生物制造。

• 发表时间: 2019
• 影响因子: 13.6
• 作者: Skylar;Uzel, Sebastien G M;Nam, Lucy L;Ahrens, John H;Truby, Ryan L;Damaraju, Sarita;Lewis, Jennifer A
• 通讯作者: Lewis, Jennifer A