We will develop a set of tools that will render bacteria deep inside the body visible to ultrasound. Bacteria play an important role in human health: The natural community of microbes in the gut contributes to metabolism and immunity, and infectious bacteria that invade the intestines can precipitate a range of conditions, from acute food poisoning to irritable bowel disease (IBD). But these bacteria are difficult to see: Detection generally involves culturing the microbes outside the body, a procedure that doesn't reveal where they are or how they interact with each other. This work is enabled by our recent discovery that a unique class of proteins can scatter sound waves in a way that makes them visible with ultrasound. These proteins evolved in certain species of bacteria and archaea as a means to regulate buoyancy. We will transfer the genes encoding these proteins into bacteria that target the gut, such as E. coli and Salmonella, and then visually monitor the engineered microbes as they colonize the intestines of mice. Being able to observe such microbes—and how the body reacts to them—could provide a new approach to diagnosing conditions such as IBD that currently require invasive colonoscopies to identify areas of inflammation.