slauch jamesResearch in the Slauch is focused on understanding the molecular mechanisms of Salmonella pathogenesis. First, Dr. Slauch is studying the regulation of the Type III Secretion System (T3SS) encoded on Salmonella Pathogenicity Island 1 (SPI1). Production of this complex machine is controlled in response to a variety of environmental signals that presumably indicate that the bacterium is in the intestine of the host. He wishes to understand how the numerous environmental parameters and global regulatory systems are integrated into the complex regulatory circuit that directly controls transcription of the secretion system genes. Second, Dr. Slauch studying the ability of Salmonella to survive in macrophages, the hallmark of serious extraintestinal infections. Macrophages normally kill bacteria by producing a variety of antimicrobials, including superoxide, but the actual mechanism of this killing is unknown. He and his laboratory have generated extensive genetic data showing that phagocytic superoxide damages an extracytoplasmic target; cytoplasmic targets including DNA seem to be irrelevant. However, he does not know the nature of the target(s). Several projects are focused on determining the targets of superoxide and the overall mechanism of bacterial inhibition.