How the dynamics of DNA shape control bacterial gene expression

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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.