John Manion, PhD

Many pathogenic bacteria secrete large proteins that target cells, enter them, and deliver enzymes that damage or rewire cells. These are known as bacterial toxins. Bacterial toxins are one of nature's most potent weapons. Our lab seeks to understand the mechanisms by which these toxins cause disease, through discovery of their cellular and molecular targets. Naturally, the purpose of these toxins is to help the bacteria through manipulation of the host, so we seek to understand how these toxins play a beneficial role for the bacteria in processes such as competition and colonization. Finally, we use these bacteria and toxins as tools to understand fundamental physiology. Due to the demands of these toxins, they target sites critical to physiological function to achieve their goals. One example is TcdB, a large toxin produced by C. difficile (a major cause of serious diarrhea after antibiotics). TcdB selectively targets sensory neurons and pericytes within the intestine through cellular receptors. Thus, toxins are a lens to understand the physiological roles that interactions between these cells play in normal and disease functions within the intestine. For example, neurons and pericytes interact at neurovascular junctions to regulate immune functions. Through the study of toxins, we can explore many aspects of physiology and build tools that allow us to hijack cellular physiology.