Nuclear Architecture and Disease

核结构与疾病

• 批准号: 7965241
• 负责人: thomas a misteli
• 金额: $ 222.52万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7965241
• 关键词: Affect; Age; Aging-Related Process; Architecture; Area; Behavior; Cell Nucleus; Cells; Chromosomal translocation; DNA; Defect; Development; Disease; Genome; Goals; Health; Interphase Cell; Laboratories; Life; Malignant Neoplasms; Methods; Molecular; Nuclear; Patients; Positioning Attribute; Premature aging syndrome; Process; Progeria; Role; Software Tools; Syndrome; System; Time; Work; base; cancer cell; cancer diagnosis; imaging modality; in vivo; normal aging; novel; tumor

The aim of our laboratory is to understand how genomes are organized in vivo and how this organization contributes to genome function in health and disease. We have made significant progress in several areas: We have extended our earlier efforts to develop imaging methods to visualize genome function in living cells. In particular, we have developed an experimental system which allows us for the first time to visualize the behavior of broken DNA regions in living cells. We have used this system to probe the mechanism by which cancer chromosome translocations occur in intact cells. We have also continued our ongoing work on exploring the spatial organization of the genome in the interphase cell nucleus. We have developed novel software tools to analyze spatial genome positioning and we have applied it to the analysis of genome organization differences in normal and cancer cells. We are applying these methods to the development of novel cancer diagnosis strategies. Finally, we are exploring the molecular mechanisms of the premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS), in particular as a means to uncover the process of aging-related tumor formation. We are exploring the mechanism by which higher order genome organization is lost in HGPS patient cells and we are investigating the molecular basis for the organismal defects in HGPS patients and during normal aging. We are also using HGPS to explore the molecular mechanisms of aging-associated cancer formation.

我们实验室的目的是了解基因组在体内是如何组织的， 该组织为基因组在健康和疾病方面的功能做出了贡献。我们取得了 在几个领域取得了重大进展：我们已经扩大了我们早期的努力， 活细胞中基因组功能可视化的方法。特别是，我们开发了一个 这是一个实验系统，它使我们能够第一次可视化断裂DNA的行为， 活细胞中的区域。我们用这个系统来探测癌症 染色体易位发生在完整的细胞中。我们还继续开展工作， 探索间期细胞核中基因组的空间组织。我们有 开发了新的软件工具来分析空间基因组定位，我们已经将其应用于 分析正常细胞和癌细胞的基因组结构差异。我们正在申请 这些方法有助于开发新的癌症诊断策略。最后，我们 探索过早衰老疾病Hutchinson-Gilford早衰症的分子机制 综合征（HGPS），特别是作为一种手段，以揭示与衰老相关的肿瘤的过程 阵我们正在探索高级基因组组织丢失的机制， HGPS患者细胞，我们正在研究HGPS患者细胞中生物缺陷的分子基础。 HGPS患者和正常衰老期间。我们也在使用HGPS来探索 与衰老相关的癌症形成机制。