The relationship between spatial nuclear organization and stochastic gene expression

空间核组织与随机基因表达之间的关系

• 批准号: 0548484
• 负责人: Alexander Van Oudenaarden
• 金额: $ 150万
• 依托单位: Massachusetts Institute of Technology
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-15 至 2011-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0548484&HistoricalAwards=false
• 关键词: relationship; between; spatial; nuclear; organization

A NSF CAREER award that started in the Summer of 2001 was used to initiate a research program on stochastic gene expression in both prokaryotic and eukaryotic organisms. One result of the work on yeast supported through this effort pointed to the importance of chromosomal positioning for regulating stochastic gene expression, thereby providing the first clue that spatial organization might play an important role for determining the stochastic properties of gene expression. This spatial aspect had generally been ignored in the earlier studies on stochastic gene expression in which the cell was considered as a well-stirred system. The general objective of the continuation of this effort is to determine the relationship between spatial nuclear organization and stochastic gene expression using the budding yeast Saccharomyces cerevisiae as a model system. The project is focused on the following specific Aims:1. Measure the correlation between expression fluctuations of two genes on the same chromosome as a function of the genomic distance between the genes.2. Measure how the correlation between expression fluctuations of two genes on the same chromosome change as one locus or several loci on this chromosome are recruited to the nuclear periphery.3. Measure the temporal correlation between the three-dimensional position of a gene locus and the corresponding expression of this gene in single cells in real time. These three projects involve both a significant mathematical and biological ingredient reflecting the interdisciplinary nature of modern biology. For example; the concept of stochastic fluctuations originates from engineering disciplines; mathematical methods are needed to implement the procedures; concepts from physics, such as diffusion, provide insight; and often codes from computer sciences enable large scale calculations. As part of the educational effort, the students trained through this project will be provided with interdisciplinary courses developed by the principal investigator that bridge the gaps between the isolated disciplines. These courses will be offered widely through the university.

2001年夏天开始的美国国家科学基金会职业奖被用来启动原核生物和真核生物中随机基因表达的研究计划。通过这项工作支持的关于酵母的工作的一个结果指出，染色体定位对于调控随机基因表达的重要性，从而提供了第一条线索，即空间组织可能在确定基因表达的随机性质方面发挥重要作用。在早期的随机基因表达研究中，细胞被认为是一个良好搅拌的系统，通常忽略了这一空间因素。继续这项工作的总体目标是以发芽酵母为模型系统，确定空间核组织和随机基因表达之间的关系。该项目主要集中在以下具体目标上：1.测量同一染色体上两个基因的表达波动之间的相关性，作为基因组之间距离的函数。当同一染色体上的一个或多个基因被招募到核外周时，测量同一染色体上两个基因表达波动之间的相关性是如何变化的。实时测量基因座的三维位置与该基因在单细胞中相应表达之间的时间相关性。这三个项目都涉及重要的数学和生物学成分，反映了现代生物学的跨学科性质。例如，随机波动的概念起源于工程学科；需要数学方法来实施这些程序；来自物理学的概念，如扩散，提供了洞察力；来自计算机科学的代码通常使大规模计算成为可能。作为教育工作的一部分，将向通过该项目培训的学生提供由首席调查员开发的跨学科课程，以弥合孤立学科之间的差距。这些课程将通过大学广泛提供。