Living cells can be thought of as extremely sophisticated machines that only function if all of the parts are in the right place. Imagine a car in which the steering wheel is in the trunk and the wheels are on the roof. Such a vehicle wouldn’t be very useful!
All protein molecules are manufactured inside the cell, but many of them must be transported across one or more membrane barriers in order to reach the location where they perform their jobs. We are currently studying a large class of bacterial proteins called autotransporters that are transported across the outer cell membrane. Once autotransporters are exposed on the cell surface, they enhance the ability of certain bacteria to cause disease. We have found that autotransporter export is a complex, multistep process involving the participation of several molecular machines that are dedicated to preparing client proteins for export, or that facilitate their physical movement across the outer cell membrane. We hope that our work will lead to the development of new strategies to block autotransporter export and thereby prevent or treat bacterial disease.
In a separate project we are trying to understand how bacteria that are benign, naturally occurring inhabitants of the human colon transport proteins into the environment. We hope that the knowledge we gain will ultimately enable us to produce modified bacteria that export specific proteins into the colon to fight diseases such as inflammatory bowel disease.