Nuclear Architecture and Disease

核结构与疾病

• 批准号: 10262065
• 负责人: thomas a misteli
• 金额: $ 265.96万
• 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/10262065
• 关键词: Affect; Aging; Architecture; Biochemical; Biological; Biological Models; Cell Nucleus; Cells; Development; Disease; Genome; Goals; Health; Human; Laboratories; Malignant Neoplasms; Maps; Methods; Molecular; Normal Cell; Nuclear; Positioning Attribute; Premature aging syndrome; Process; Progeria; Role; Sampling; Software Tools; Syndrome; Tissues; cancer cell; genome analysis; imaging approach; imaging modality; in vivo; novel; screening

The aim of the Misteli laboratory is to understand how genomes are organized in vivo and how the architectural organization of the genome contributes to its function in health and disease. To this end, we are employing cell biological and biochemical methods and we are developing advanced imaging methods to probe genome organization in living cells and tissues. In particular, we are taking advantage of high-throughput imaging approaches to map genome regions with high precision in a large number of samples allowing for systematic spatial mapping and implementation of screening approaches for discovery. We have also 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. Finally, we are exploring the molecular mechanisms of human aging and the relationship between aging and cancer. We use the rare premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS) as a model system in these studies.

Misteli实验室的目的是了解基因组在体内是如何组织的，以及基因组的结构组织如何有助于其在健康和疾病中的功能。为此，我们正在采用细胞生物学和生物化学方法，并正在开发先进的成像方法来探测活细胞和组织中的基因组组织。特别是，我们正在利用高通量成像方法在大量样本中高精度地绘制基因组区域，以便进行系统的空间绘制和实施发现的筛选方法。我们还开发了新的软件工具来分析空间基因组定位，并将其应用于正常细胞和癌细胞基因组组织差异的分析。最后，我们正在探索人类衰老的分子机制以及衰老与癌症之间的关系。在这些研究中，我们使用罕见的过早衰老疾病Hutchinson-Gilford早衰综合征（HGPS）作为模型系统。