基因转录爆发的产生机制及其生物学功能研究

项目名称： 基因转录爆发的产生机制及其生物学功能研究

项目编号： No.11475273

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 数理科学和化学

项目作者： 张家军

作者单位： 中山大学

项目金额： 80万元

中文摘要： 揭示基因表达机制既是朝着理解细胞过程的重要一步，也对理解细胞功能是本质性的。传统的群体测量技术与分析方法掩盖了个体细胞之间的差异性，而单细胞测量技术为研究个体细胞内的基因表达过程提供了丰富的数据支撑。本项目针对单细胞测量技术所揭示的精细分子机制，从生物物理学的角度对基因表达动力学以及由转录爆发造成的细胞非遗传异质性的生物学功能开展深入研究，聚焦于转录爆发的产生机制，转录爆发在细胞命运决策过程中的作用，以及转录爆发对细胞分化的影响。具体来说，我们将研究启动子调控序列如何决定转录过程中的随机特性以及如何导致mRNA和蛋白质水平的随机涨落；以细菌细胞中KatG作用模型为例，研究转录爆发在细菌抗药过程中是如何抉择细胞命运的；以骨肉瘤干细胞为例，研究转录爆发是如何决定基因显性的。通过细致研究，我们试图阐明细胞的非遗传异质性的产生源，以及揭示出非遗传异质性的本质生物学功能。

中文关键词： 生物物理；随机基因表达；基因转录；数学建模；统计物理学

英文摘要： Revealing the mechanism of how genes are expressed is not only essential for understanding cellular functions but also an important step forward understanding intracellular processes.Traditional population measurement technolgies and analysis methods mask differences between individual cells whereas single-cell measurement technologies provide rich data support for studying gene expression processes in single cells. Aiming to elaborate molecular mechanisms revealed by single-cell measurement technologies, this project conducts, from viewpoints of biophysics,deep studies on dynamics of gene expression as well as biological functions of non-genetic heterogeneity resulting from transcriptional burst, focusing on the generation mechanism of transcription burst, role of transcriptional burst in decision-making of cell fates and influence of transcriptional burst on cell differentiation. More specifically, we will study how the regulatory sequences of promoters determine stochastic characteristics of transcription processes as well as how these sequences result in stochastic fluctuations in mRNA or protein content; how transcriptional burst strategizes cell fates in baterical resistance to antimicrobialas using a KatG model of bacterial cells; and how transcriptional burst decides epigenesis of genes in Osteosarcoma stem cells. Through detailed studies, we try to elucidate the source of generating non-genetic heterogeneity in single cells and reavel the essential biological functions of non-genetic heterogeneity.

英文关键词： biophysics;stochastic gene expression;transcription;mathematical modelling;statistical physics