Career: Live Cell Imaging Of Salmonella Effector Proteins

<p>Intellectual merit: This project will develop a powerful, novel approach to illuminate how disease-causing (pathogenic) bacteria invade host organisms. A wide range of bacterial pathogens use a set of proteins, called effectors, to invade and infect host cells. Upon entry, these effector proteins work cooperatively to hijack cellular signaling and to reprogram the host cell to enable bacterial survival. Over 60 effector proteins have been identified that are injected into the host cell through a complex macromolecular machine known as the Type Three Secretion System (T3SS). Although these effector proteins are essential for mediating invasion and manipulating host cell biology, it is not fully understood how they work because there are no methods to visualize their movements in real-time during cellular invasion. This project will develop a new method that will directly tag the broad spectrum of effector proteins with fluorescent molecules in order to visualize their movements during infection of a host cell. The focus of this project is Salmonella enterica, but the method that will be developed could potentially transform the understanding of the mechanism of infection for a wide variety of other pathogens that utilize a T3SS to infect host organisms and will further contribute to the scientific understanding of protein secretion by bacteria.
<br>Broader impacts: This project will contribute to a campus-wide effort to reform undergraduate science education by strengthening interdisciplinary, hands-on tutorials that will promote student engagement and transform student learning. These materials will have a direct and powerful impact on the way physical and biophysical chemistry are taught. Biological applications (such as visualization of bacterial invasion) will be used as case studies to inspire students to appreciate the diversity of physical chemistry applications. One of the greatest impacts will be to train, mentor, and motivate the next generation of scientists. The scientific and educational research will be performed entirely by graduate and undergraduate students and will provide fertile ground for training students to see fundamental connections between different scientific disciplines and to create novel tools that help address fundamental biological/educational questions. Moreover, this project aims to transform undergraduate biology and physical chemistry curricula, which will affect hundreds of students at the University of Colorado, Boulder, and many more across the country since the materials developed will be made widely available online for the educational community.</p>