Core 2: Mammalian Artificial Chromosome (MAC)

核心 2：哺乳动物人工染色体 (MAC)

• 批准号: 10626286
• 负责人: Ben E. Black
• 金额: $ 36.48万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10626286
• 关键词: Address; Animals; Artificial Human Chromosomes; Artificial Mammalian Chromosomes; Award; Biology; Cancer Biology; Categories; Cell Cycle; Cell division; Cells; Centromere; Chemicals; Chromatin; Chromatin Modeling; Chromosome Segregation; Chromosomes; Cloning; Cytoplasm; DNA; DNA Damage; DNA Sequence; DNA cassette; DNA sequencing; Engineered Gene; Engineering; Epigenetic Process; Essential Genes; Event; Gene Dosage; Generations; Genes; Genetic; Genetic Recombination; Genome; Genomic Instability; Genomics; Housing; Human Genome; Individual; Inherited; Lead; Mitosis; Mitotic; Mitotic Chromosome; Molecular; Molecular Biology; Monitor; Mus; Nature; Organoids; Outcome; Process; Proteins; Regulatory Element; Reporter; Reporting; Saccharomycetales; Sister Chromatid; Site; System; Technology; Work; anti-tumor immune response; cell type; chemical genetics; chromosome missegregation; design; design and construction; embryonic stem cell; epigenomics; experimental study; falls; flexibility; genetic information; genetic payload; genomic locus; immunoregulation; improved; innovation; member; micronucleus; next generation; patient response; predictive marker; programs; response; segregation; synthetic biology; therapy resistant; tool; tumor

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.

哺乳动物人造染色体（MAC）核心将支持整个项目，该项目旨在解决该项目 DNA损伤细胞和动物的下游后果，原因和后果 细胞分裂的染色体错误分类，以及驱动这些过程中肿瘤过程的机制。会 充当Mac的铸造厂，将支持每个需要染色体的单个项目 操纵和工程：从位于定位和可诱导的DNA损害到染色体的记者 隔离误差，以容纳化学遗传学工具箱的遗传编码成分。 Mac可以 携带较大（即100-2000 kb）的遗传有效载荷，并存在细胞中，作为传播和 与天然染色体旁继承。他们的自主性是一个关键优势，因为他们交付 他们的基因有效载荷无插入或宿主基因组的其他破坏。核心将采用我们最近的 Mac技术的创新引起了新一代MAC模板，我们指导该模板 丝粒染色质的播种。这种方法允许在不同的DNA模板上有效地形成MAC。 核心将从其设计，创建，传递到细胞，表征， 通过他们实施计划的各个项目中提出的实验。具体来说， 核心将开发和使用属于以下类别的MAC：作为DNA的目标的核心 损坏，具有精心制作的基因有效载荷的损害，可以调节染色体隔离 具有复杂程度的程度，以及具有荧光记录的染色体错误分析的记者。 Mac 核心旨在灵活地帮助项目成员开发新的实验线 在整个程序的初始步骤中实现的发现。