Horizontal transfer of genes from one species to another is thought to be an important cause of rapid genetic change, as it can afford the recipient a new but functional gene in a single step. While the processes of gene exchange between species are often obscure, in rare naturally transformable bacteria, an efficient mechanism of horizontal gene transfer is directly accessible to experimental analysis. This project studies such a horizontal gene transfer process, found in Streptococcus pneumoniae. This inhabitant of the human nasopharynx can enter a temporary special physiological state, competence, in which DNA is efficiently taken into the cell, and many of its genes may be replaced by related genes from such donor DNA molecules. The project will determine how this natural analog of gene therapy is coordinated so that all cells of a bacterial culture simultaneously develop competence. S. pneumoniae employs a peptide pheromone signal for cell-to-cell communication to count the bacterial population size and coordinate the activities of cells in a culture. This research seeks to learn how the population density signal is transmitted to the cell interior. It studies a global regulator of gene expression that carries the population signal to over 100 individual genes. Using genetic strategies to identify key regulatory proteins, and biochemical methods to study them, it will reveal new information about the role of regulated protein degradation in control of RNA polymerase specificity. Beyond fundamental science, the project has broader impacts on several levels. It will, for example, help to define the minimum gene set needed for DNA transport and gene exchange, key elements of genetic engineering. As this project increases the understanding of horizontal gene transfer, it also provides important genetic tools for use in applied studies of S. pneumoniae, with possible impacts on the understanding, treating, and preventing disease. Finally, it intimately integrates research and education: every experiment in this project is done by a student at some level of training, mainly undergraduates and doctoral candidates in Molecular Biology.
