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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要同源染色体配对是孟德尔遗传的核心过程，但同时许多遗传学研究揭示了参与同源识别和重组的基因、物理染色体在密集的细胞核内聚集在一起的过程仍然很糟糕明白了。减数分裂染色体的端粒锚定在核膜上并附着在细胞骨架，施加随机定向的拉力。一个关键问题是如何随机定向力可以促进同源性搜索过程。使用一系列计算模型，我们证明了理论上，随机定向的端粒力可以通过多种方式促进搜索：驱动超扩散运动染色质，克服缠结，取消配对不正确的区域以提高保真度，并反对染色体的熵分离。我们建议使用活细胞测试这些不同的预测功能成像和定量图像分析，结合酵母遗传学来改变施加在染色体。我们的结果不仅应该影响减数分裂同源配对作为物理方法的理解过程，而且还包括一般染色体运动的物理生物学以及主动的广泛概念生物学中的随机运动。