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Holistic approach to the bacterial genetic regulation system

细菌遗传调控系统的整体方法

基本信息

批准号：
243154253
负责人：
Professor Dr. Georgi Muskhelishvili
金额：
--
依托单位：
Laboratoire de Microbiologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2013
资助国家：
德国
起止时间：
2012-12-31 至 2016-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/243154253?language=en
关键词：
Holistic approach bacterial genetic regulation

项目摘要

Exploration of the bacterial genetic regulation system is central for the advancement of both systems and synthetic biology and for establishing efficient knowledge-based approaches in biotechnology and biomedicine. Vigorous international research employing high-throughput technologies revealed the true complexity of the problem and a critical need for an appropriate methodological approach integrating different structural and organisational features of the genetic regulation system. At the bottom line, the major requirement is to understand the control of information flow in the genetic system. We have developed a new holistic methodology integrating the DNA sequence organization, DNA topology, gene order, gene function and the dynamics of interactions between the regulators and their targets in chromosomal macrodomains. Using this methodology we recently provided a first mechanistic insight into how the organization of a complete bacterial chromosome encodes a spatiotemporal program integrating DNA replication and global gene expression. Our work illuminated why the timing of the expression of a gene is linked to its position on the bacterial chromosome and provided a view of the nucleoid as a highly organized dynamic entity optimized for coordinating oxygen and nutrient availability with spatiotemporal gene expression during rapid growth and its cessation. The prediction is that during the bacterial growth cycle reorganization of transcription is driven by a spatiotemporal gradient of DNA superhelical density from the origin to terminus of chromosomal replication. This gradient is modulated by compositional changes of the abundant nucleoid-associated proteins (NAPs), which constrain DNA supercoils in variable chromosomal regions thus coordinately reorganizing the chromosomal shape and transcription. The observed regional effects on transcription in the bacterial chromosome suggest that strategic positioning of regulatory genes may provide new powerful means for controlling bacterial gene expression and adaptation. The work intended in this project aims to provide such novel tools crucial for implementing knowledge-based approaches in a range of related fields concerned with both fundamental and applied aspects of the bacterial gene regulation.

细菌遗传调控系统的探索对于系统和合成生物学的发展以及建立生物技术和生物医学中有效的基于知识的方法至关重要。采用高通量技术的国际研究显示了问题的真正复杂性，并迫切需要一种适当的方法，将遗传调控系统的不同结构和组织特征结合起来。归根结底，主要的要求是了解遗传系统中信息流的控制。我们已经开发了一种新的整体方法，整合了DNA序列组织，DNA拓扑结构，基因顺序，基因功能和染色体宏域中的调节剂和它们的目标之间的相互作用的动力学。使用这种方法，我们最近提供了一个完整的细菌染色体的组织如何编码整合DNA复制和全球基因表达的时空程序的第一个机制的见解。我们的工作阐明了为什么基因表达的时间与其在细菌染色体上的位置有关，并提供了一个观点，即类核是一个高度组织化的动态实体，在快速生长和停止过程中，它被优化用于协调氧气和营养物质的可用性与时空基因表达。预测是，在细菌生长周期中，转录的重组是由DNA超螺旋密度从染色体复制的起点到终点的时空梯度驱动的。这种梯度由丰富的核苷酸相关蛋白（NAP）的组成变化来调节，这些蛋白将DNA超螺旋限制在可变的染色体区域中，从而协调重组染色体形状和转录。观察到的区域效应在细菌染色体的转录表明，战略定位的调控基因可能提供新的强大的手段，控制细菌基因的表达和适应。本项目的工作旨在提供这些新的工具，这些工具对于在与细菌基因调控的基础和应用方面有关的一系列相关领域中实施基于知识的方法至关重要。