Structural characterization of the bacterial flagellum basal body

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Many bacteria utilize a long, rotating filament on their surface, called the flagellum, to swim in their surrounding environment, and for adherence to solid surfaces. In particular, these features are essential for many pathogenic bacteria such as E.coli, Salmonella, Shigella etc.. to cause disease. This is because the flagellum allows them to spread in the host's body, and to adhere to their cells, as well as to medical devices such as catheters. As a consequence, understanding the bacterial flagellum at the molecular level could have numerous medical implication, and disrupting its rotation and adherence properties would largely reduce infection in a clinical setting. However, the flagellum is a very sophisticated nano-machine, and studying its mechanism of action at the molecular level is particularly challenging. A central region of the flagellum, called the "basal body", serves as an anchoring point around which the complete machinery forms. Despite the importance of this region, we know very little about its molecular details, and about how its constituting components come together to form a stable platform around which the flagellum assembles. The objective of the proposed research is to use advanced biophysics methods, including the most cutting-edge electron microscopy techniques, to generate a molecular "map" of the flagellum basal body. We will then exploit this map to determine how its constituting components come together to form such a sophisticated structure. These results could be exploited to generate new therapies that block the formation or function of the flagellum. This would be of particular interest because the flagellum is widespread amongst bacteria, and therefore such therapy could target infections from a wide range of bacteria. In addition, a molecular map of the basal body will provide clues of how bacteria were able to "evolve" structures such as the flagellum, by comparison to other known nano-machines. Finally, understanding how the flagellum forms could be used to develop motile drug delivery systems, which could be exploited for a wide range of medication such as anticancer treatment or gene therapies.