Quantitative Analysis of Meiotic Chromosome Motion and Pairing

减数分裂染色体运动和配对的定量分析

• 批准号: 10378113
• 负责人: JENNIFER C FUNG
• 金额: $ 36.34万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-03 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10378113
• 关键词: Articular Range of Motion; Automobile Driving; Biological; Biological Phenomena; Biological Process; Biology; Cell Nucleus; Cells; Centromere; Chromatin; Chromosome Pairing; Chromosome Segregation; Chromosomes; Computer Analysis; Computer Models; Computer Simulation; Crowding; Cytoskeleton; DNA Sequence; Data; Development; Developmental Disabilities; Diagnostic tests; Elements; Ensure; Entropy; Environment; Future; Genes; Genetic; Genetic Recombination; Genetic study; Goals; Homologous Gene; Human; Image Analysis; Infertility; Lead; Length; Measurement; Measures; Medical; Meiosis; Mental Retardation; Mitotic; Modeling; Molecular; Motion; Movement; Nuclear Envelope; Operative Surgical Procedures; Play; Polymers; Process; Research; Role; Saccharomycetales; Sequence Homology; Series; Testing; Work; X Inactivation; chromosome missegregation; chromosome movement; design; driving force; homologous recombination; improved; infertility treatment; live cell imaging; mechanical force; melting; physical process; prevent; quantitative imaging; simulation; telomere; theories; yeast genetics

Project Summary Homologous chromosome pairing is a central process underlying Mendelian inheritance, but while many genetic studies have revealed genes involved in homology recognition and recombination, the physical process by which the chromosomes come together inside the densely packed nucleus remains poorly understood. Telomeres of meiotic chromosomes are anchored on the nuclear envelope and attached to the cytoskeleton, which exerts randomly directed pulling forces. A key question is how randomly directed forces can facilitate the homology search process. Using a series of computational models, we have shown that randomly directed telomere forces can in theory promote search in several ways: driving superdiffusive motion of chromatin, overcoming entanglement, unpairing incorrectly paired regions to improve fidelity, and opposing entropic de-mixing of chromosomes. We propose to test these distinct predicted functions using live cell imaging and quantitative image analysis, combined with yeast genetics to alter the forces applied to the chromosomes. Our results should impact not only the understanding of meiotic homolog pairing as a physical process, but also the physical biology of chromosome motion in general as well as the broad concept of active random motion in biology.

项目摘要 同源染色体配对是孟德尔遗传的核心过程， 许多遗传学研究揭示了参与同源识别和重组的基因， 染色体在密集的细胞核内聚集的过程仍然很差， 明白减数分裂染色体的端粒锚定在核膜上，并附着在细胞核上。 细胞骨架，其施加随机定向的拉力。一个关键问题是随机定向的力 可以促进同源性搜索过程。使用一系列计算模型，我们已经表明， 随机定向的端粒力在理论上可以通过几种方式促进搜索：驱动超扩散运动 染色质，克服纠缠，取消配对不正确的配对区域，以提高保真度， 染色体的熵解混。我们建议使用活细胞来测试这些不同的预测功能 成像和定量图像分析，结合酵母遗传学，以改变施加在细胞上的力。 染色体我们的结果不仅会影响对减数分裂同源配对的理解， 过程，而且也是染色体运动的物理生物学一般以及广泛的概念，积极的 生物学中的随机运动