Grant: Discovery Grants Program - Individual

In all life-forms, an enzyme complex called RNA polymerase is responsible for the expression of genes in cells. In bacteria, this complex itself cannot bind to DNA and it requires another enzyme subunit called sigma factor. Sigma factors bind RNA polymerase forming what is called holoenzyme and holoenzyme is capable of binding the promoter region of each gene and activating gene expression. Each bacterial species encodes one or more sigma factors that together ensure the coordinated expression of all genes in the cell. Our lab studies the molecular function of sigma factors including unusual forms of this protein found in some species. Recently, we discovered an unusual form of sigma factor in the model bacterium Bacillus subtilis. This sigma factor is composed of two individual proteins called YvrI and YvrHa and these enzymes work together to catalyze what is usually accomplished by a single protein sigma factor in holoenyzme. Our research plan proposes a series of projects that will help explain how this unusual two-subunit sigma factor interacts with RNA polymerase, and how the resulting holoenzyme recognizes and binds DNA to activate gene expression. We are also examining the DNA-binding site for YvrI-YvrHa based holoenzyme. Understanding how genes are expressed in bacteria is important for understanding the molecular nature of life and for many pursuits in industry and medicine including the discovery of new antibiotics.