Core 2: Mammalian Artificial Chromosome (MAC)
核心 2:哺乳动物人工染色体 (MAC)
基本信息
- 批准号:10626286
- 负责人:
- 金额:$ 36.48万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-05-08 至 2028-04-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAnimalsArtificial Human ChromosomesArtificial Mammalian ChromosomesAwardBiologyCancer BiologyCategoriesCell CycleCell divisionCellsCentromereChemicalsChromatinChromatin ModelingChromosome SegregationChromosomesCloningCytoplasmDNADNA DamageDNA SequenceDNA cassetteDNA sequencingEngineered GeneEngineeringEpigenetic ProcessEssential GenesEventGene DosageGenerationsGenesGeneticGenetic RecombinationGenomeGenomic InstabilityGenomicsHousingHuman GenomeIndividualInheritedLeadMitosisMitoticMitotic ChromosomeMolecularMolecular BiologyMonitorMusNatureOrganoidsOutcomeProcessProteinsRegulatory ElementReporterReportingSaccharomycetalesSister ChromatidSiteSystemTechnologyWorkanti-tumor immune responsecell typechemical geneticschromosome missegregationdesigndesign and constructionembryonic stem cellepigenomicsexperimental studyfallsflexibilitygenetic informationgenetic payloadgenomic locusimmunoregulationimprovedinnovationmembermicronucleusnext generationpatient responsepredictive markerprogramsresponsesegregationsynthetic biologytherapy resistanttooltumor
项目摘要
The mammalian artificial chromosome (MAC) Core will support the overall Project, which seeks to address the
downstream consequences in cells and animals of DNA damage, the causes and consequences of
chromosome missegregation at cell division, and the mechanisms that drive these processes in tumors. It will
serve as a foundry for MACs that will support each of the individual projects that require chromosome
manipulations and engineering: from site-directed and inducible DNA damage, to reporters for chromosome
segregation errors, to housing the genetically encoded components of a chemical genetics toolbox. MACs can
carry large (i.e. 100-2000 kb) genetic payloads, and exist in cells as molecules that are propagated and
inherited alongside the natural chromosomes. Their autonomous nature is a key advantage, since they deliver
their genetic payloads without insertion or other disruption of the host genome. The Core will employ our recent
innovations in MAC technology that gave rise to a new generation of MAC templates in which we direct the
seeding of centromeric chromatin. This approach permits efficient MAC formation on diverse DNA templates.
The Core will undertake MAC approaches from their design, creation, delivery into cells, characterization,
through to their implementation for experiments proposed in the individual Projects of the program. Specifically,
the Core will develop and use MACs that fall into the following categories: ones that serve as targets for DNA
damage, ones that harbor elaborate genetic payloads that will modulate chromosome segregation with a high
degree of sophistication, and ones that carry fluorescent reporters of chromosome missegregation. The MAC
Core is designed to be flexible to help Project members develop new lines of experimentation that arise from
the findings achieved during the initial steps in the overall program.
哺乳动物人工染色体(MAC)核心将支持整个项目,该项目旨在解决
DNA损伤的细胞和动物的下游后果,
细胞分裂时的染色体错误分离,以及在肿瘤中驱动这些过程的机制。它将
作为MAC的铸造厂,将支持每个需要染色体的单独项目
操作和工程:从定点和诱导型DNA损伤,到染色体报告基因
分离错误,以容纳化学遗传学工具箱的遗传编码组件。MAC可以
携带大的(即100-2000 kb)遗传有效载荷,并作为增殖和
与自然染色体一起遗传。他们的自主性是一个关键的优势,因为他们提供
它们的遗传有效载荷而不插入或破坏宿主基因组。核心会雇佣我们最近的
MAC技术的创新,产生了新一代MAC模板,我们在其中指导
着丝粒染色质的接种。这种方法允许在不同的DNA模板上有效地形成MAC。
核心将承担MAC方法,从他们的设计,创造,交付到细胞,表征,
通过他们的实施,在该计划的个别项目提出的实验。具体地说,
“核心”将开发和使用可分为以下几类的MAC:作为DNA靶点的MAC
损害,那些窝藏精心设计的遗传有效载荷,将调节染色体分离与高
复杂程度,和那些携带染色体错误分离的荧光报告。的MAC
核心是设计灵活,以帮助项目成员开发新的实验线,产生于
在整个方案的最初阶段取得的成果。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Ben E. Black其他文献
A high-resolution look at fresh human brain vitrified directly from autopsy using cryo-electron tomography with cryo-plasma focused ion beam milling
- DOI:
10.1016/j.bpj.2023.11.1192 - 发表时间:
2024-02-08 - 期刊:
- 影响因子:
- 作者:
Benjamin C. Creekmore;Kathryn Kixmoeller;Ben E. Black;Edward B. Lee;Yi-Wei Chang - 通讯作者:
Yi-Wei Chang
A PARP2 active site helix melts to permit DNA damage-induced enzymatic activation
PARP2 活性位点螺旋熔化以允许 DNA 损伤诱导的酶促激活
- DOI:
10.1016/j.molcel.2025.01.004 - 发表时间:
2025-03-06 - 期刊:
- 影响因子:16.600
- 作者:
Emily S. Smith-Pillet;Ramya Billur;Marie-France Langelier;Tanaji T. Talele;John M. Pascal;Ben E. Black - 通讯作者:
Ben E. Black
Remodeling of inner kinetochore components at mitotic onset is required for chromosome segregation
- DOI:
10.1016/j.bpj.2023.11.2240 - 发表时间:
2024-02-08 - 期刊:
- 影响因子:
- 作者:
Praveen Kumar Allu;Lucie Y. Guo;Rachel M. Lackner;David M. Chenoweth;Ben E. Black - 通讯作者:
Ben E. Black
Satellite DNA shapes dictate pericentromere packaging in female meiosis
卫星 DNA 形状决定着女性减数分裂中着丝粒周围区域的包装
- DOI:
10.1038/s41586-024-08374-0 - 发表时间:
2025-01-08 - 期刊:
- 影响因子:48.500
- 作者:
Damian Dudka;Jennine M. Dawicki-McKenna;Xueqi Sun;Keagan Beeravolu;Takashi Akera;Michael A. Lampson;Ben E. Black - 通讯作者:
Ben E. Black
Centromeric chromatin clearings demarcate the site of kinetochore formation
着丝粒染色质间隙划定了动粒形成的位点。
- DOI:
10.1016/j.cell.2024.12.025 - 发表时间:
2025-03-06 - 期刊:
- 影响因子:42.500
- 作者:
Kathryn Kixmoeller;Ekaterina V. Tarasovetc;Elie Mer;Yi-Wei Chang;Ben E. Black - 通讯作者:
Ben E. Black
Ben E. Black的其他文献
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{{ truncateString('Ben E. Black', 18)}}的其他基金
Tuning PARP-1 retention and release on DNA breaks
调节 DNA 断裂时 PARP-1 的保留和释放
- 批准号:
10363534 - 财政年份:2022
- 资助金额:
$ 36.48万 - 项目类别:
Tuning PARP-1 retention and release on DNA breaks
调节 DNA 断裂时 PARP-1 的保留和释放
- 批准号:
10581522 - 财政年份:2022
- 资助金额:
$ 36.48万 - 项目类别:
Structural biology and molecular biophysics training program
结构生物学和分子生物物理学培训计划
- 批准号:
10630348 - 财政年份:2019
- 资助金额:
$ 36.48万 - 项目类别:
Structural biology and molecular biophysics training program
结构生物学和分子生物物理学培训计划
- 批准号:
10192759 - 财政年份:2019
- 资助金额:
$ 36.48万 - 项目类别:
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