How the dynamics of DNA shape control bacterial gene expression

DNA包含的基因是所有生物的蓝图。不太为人所知的是，DNA不仅仅是存储信息：它还在决定何时表达其携带的信息方面发挥着积极作用。这种对基因表达的控制是通过DNA的三维塑造和弯曲实现的。我们的实验室研究细菌如何利用DNA的动态塑造来应对环境的变化。换句话说，我们研究允许细菌感知、解释并随后对环境做出反应的分子机制。了解这些机制对于确定为什么一些“好”细菌突然变得“坏”并导致感染，抗生素耐药性和致病基因在不同物种中如何发挥作用，以及如何在细菌中构建基因网络以用于生物修复和工业应用至关重要。*在这项授权中，我们将研究蛋白质识别和结合DNA靶标的分子机制，DNA形状如何影响这些相互作用，以及反过来，蛋白质结合如何改变DNA形状。我们将研究模式细菌流感嗜血杆菌、大肠杆菌和肠沙门氏菌，因为在实验室中可以使用强大的遗传工具来操纵这些生物。这项工作将使用尖端基因组学技术在全基因组范围内可视化蛋白质和DNA功能，以及使用分子生物学技术来表征蛋白质与DNA的相互作用。这项研究具有深远的意义，因为我们研究的基本分子机制适用于所有生物体。

DNA contains the genes that are the blueprints for all living things. Less well known is that DNA does more than store information: it also plays an active role in deciding when to express the information it carries. This control of gene expression occurs through the 3-dimensional shaping and bending of DNA. Our lab studies how bacteria use the dynamic shaping of DNA to respond to changes in their environment. In other words, we research the molecular mechanisms that allow bacteria to perceive, interpret, and then respond to their surroundings. Understanding these mechanisms is critical for determining why some "good" bacteria suddenly turn "bad" and cause infection, how antibiotic resistance and pathogenicity genes function in different species, and how gene networks can be engineered in bacteria for bioremediation and industrial applications.****In this grant we will study the molecular mechanisms by which proteins recognize and bind their DNA targets, how DNA shape influences these interactions, and, conversely, how protein binding modifies DNA shape. We will study the model bacteria Haemophilus influenzae, Escherichia coli, and Salmonella enterica because of the powerful genetic tools available for manipulating these organisms in the lab. This work will employ cutting-edge genomics techniques for visualizing protein and DNA function on a genome-wide scale, as well as molecular biology techniques for characterizing protein-DNA interactions. This research has far-reaching implications because the fundamental molecular mechanisms we study operate in all organisms.******