Center for Genomically Engineered Organs
Center for Genomically Engineered Organs
批准号:
9928553
负责人:
GEORGE M CHURCH
金额:
$3.56万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2015
资助国家:
美国
项目状态:
已结题
起止时间:
2015-09-21 至 2020-06-30
关键词:
AddressAlgorithmsAnimal ModelAnimalsArchitectureAreaBiologicalBiological ModelsBiologyBiomedical ResearchBlood VesselsBostonCell Differentiation processCellsCellular StructuresChurchClinical TrialsCollaborationsComplementComplexComputational algorithmComputer-Aided DesignDNADataDevelopmentDiseaseEmbryoEmbryonic DevelopmentEngineeringEpigenetic ProcessGenerationsGenetic TranscriptionGenome engineeringGenomicsGerm LinesGoalsHealthHematopoiesisHumanIn SituIn VitroIndividualInstitutesKnowledgeLaboratoriesLocationMethodsMicroscopyModelingMolecularMolecular ProfilingMusNeurobiologyNormal tissue morphologyOrganOrganoidsPathologicPathway interactionsPatternPediatric HospitalsPhysiologicalPrincipal InvestigatorProcessProductionPropertyProteinsProteomicsRNAReadingReagentResearchResearch PersonnelResolutionSpecific qualifier valueStem cellsStructureSystemTechnologyTestingTimeTissue EngineeringTissue ModelTissuesTranslatingWorkWritingcell typecostdesigneffective therapyembryo tissueepigenomicsexperimental studygenome editingimprovedinnovationmedical schoolsnovelprofessorprogramsprotein expressionprotein profilingsingle cell proteinsstemstem cell differentiationstem cell technologytechnology developmenttheories
中文摘要
基因组工程器官中心(CGEO)将联合收割机结合尖端基因组学、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
将在实验室中通过重新编程或遗传修饰的干细胞或其他细胞生产,将包含
多种细胞类型和血管,并将设计和严格比较自然(健康或
患病的)组织,使得它们在分子水平和整体组织结构上紧密匹配。这些
模型组织有可能通过为研究人员提供一种方法,
进行有关正常和疾病生物学的理论的初步测试,快速和廉价的,在他们的
在他们不得不转向对动物或人类进行昂贵且可能具有侵入性的实验之前,他们必须先在实验室里进行实验。
CGEO的研究分为三个目标。在目标1中,性别平等问题总干事将制定方法,
通过获得高通量RNA表达、蛋白质表达
和表观基因组数据一起在组织的各个细胞中,沿着这些基因组数据的位置,
这些细胞中的分子。在目标2中,总地理环境干事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天然对应物进行比较,
不仅系统地比较了它们相应的细胞类型分子谱的匹配程度,
它们的整体细胞结构和关系。这些算法还将指定基因组编辑和
工程化可用于改善模型组织中的工程化细胞与
天然组织的天然细胞。CGEO将应用这些技术建立重要的模型组织,
神经生物学和造血,最后,在目标3中,还将它们应用于体外培养的胚胎和生殖
线组织在小鼠中,这有可能揭示的途径,将使所有组织的模型,
在实验室里产生的。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。政府平等事务总干事小组包括:
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(麻省理工学院),乔治戴利(儿童医院),和詹妮弗刘易斯(威斯康星大学威斯康星研究所
哈佛)。
英文摘要
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).
期刊论文(7)
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DOI:
10.1038/s41467-021-23576-0
发表时间:
2021-05-28
期刊:
Nature communications
影响因子:
16.6
作者:
[Xiang X, Corsi GI, Anthon C, Qu K, Pan X, Liang X, Han P, Dong Z, Liu L, Zhong J, Ma T, Wang J, Zhang X, Jiang H, Xu F, Liu X, Xu X, Wang J, Yang H, Bolund L, Church GM, Lin L, Gorodkin J, Luo Y]
通讯作者:
Luo Y
DOI:
10.1038/nrg.2017.59
发表时间:
2017-12
期刊:
Nature reviews. Genetics
影响因子:
--
作者:
[Chari R, Church GM]
通讯作者:
Church GM
DOI:
10.1016/j.cell.2022.08.012
发表时间:
2022-09-15
期刊:
CELL
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.
DOI:
10.1038/s41467-022-31543-6
发表时间:
2022-07-13
期刊:
Nature communications
影响因子:
16.6
作者:
[]
通讯作者:
Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels
DOI:
10.1126/sciadv.aaw2459
发表时间:
2019-09-01
期刊:
SCIENCE ADVANCES
影响因子:
13.6
作者:
[Skylar-Scott, Mark A., Uzel, Sebastien G. M., Lewis, Jennifer A.]
通讯作者:
Lewis, Jennifer A.
Single-Molecule Electronic Nucleic Acid Sequencing-by-Synthesis Using Novel Tagged Nucleotides and Nanopore Constructs
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批准号:10170406
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项目类别:
-
资助金额:$51.89万
-
财政年份:2020
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负责人:GEORGE M CHURCH
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依托单位:
Single-Molecule Electronic Nucleic Acid Sequencing-by-Synthesis Using Novel Tagged Nucleotides and Nanopore Constructs
-
批准号:10381535
-
项目类别:
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资助金额:$56.08万
-
财政年份:2020
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负责人:GEORGE M CHURCH
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依托单位:
Single-Molecule Electronic Nucleic Acid Sequencing-by-Synthesis Using Novel Tagged Nucleotides and Nanopore Constructs
-
批准号:10021992
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项目类别:
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资助金额:$25.0万
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财政年份:2019
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负责人:GEORGE M CHURCH
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依托单位:
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批准号:9357685
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财政年份:2016
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Exploring a Novel Paradigm of Schizophrenia and Bipolar Disorder
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批准号:9981018
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负责人:GEORGE M CHURCH
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依托单位:
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依托单位:
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财政年份:2013
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依托单位:
An Integrated System for Single Molecule Electronic Sequencing by Synthesis
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批准号:8728991
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项目类别:
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财政年份:2013
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依托单位:
An Integrated System for Single Molecule Electronic Sequencing by Synthesis
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批准号:8919436
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项目类别:
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资助金额:$170.62万
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财政年份:2013
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负责人:GEORGE M CHURCH
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依托单位:
Causal Transcriptional Consequences of Human Genetic Variation
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批准号:7849826
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项目类别:
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资助金额:$427.31万
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财政年份:2010
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负责人:GEORGE M CHURCH
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依托单位:
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批准号:8309490
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资助金额:$373.44万
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负责人:GEORGE M CHURCH
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批准号:8535284
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项目类别:
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资助金额:$353.04万
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财政年份:2010
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负责人:GEORGE M CHURCH
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依托单位:
Causal Transcriptional Consequences of Human Genetic Variation
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批准号:8712532
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项目类别:
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资助金额:$358.12万
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财政年份:2010
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负责人:GEORGE M CHURCH
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依托单位:
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批准号:8141976
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依托单位:
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批准号:8792903
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项目类别:
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资助金额:$3.6万
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财政年份:2010
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负责人:GEORGE M CHURCH
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依托单位:
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批准号:7854116
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财政年份:2009
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负责人:GEORGE M CHURCH
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依托单位:
Comparative phenotypic, functional, and molecular analysis of ESC and iPSC
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