Structural analysis of the Legionella pneumophila type IV secretion system by single particle cryo-electron microscopy.

Legionella pneumophila, (the causative agent of Legionnaires' disease) developed a specialized type IV secretion system (T4SS), to transport >300 toxins, into host cells (Costa et al, Nat Rev Micro, 2015). Some of the characterized translocated toxins play a critical role in hijacking host cellular pathways to establish the intracellular niche where the bacteria survive, replicate and ultimately cause disease.
The goal of the project is to investigate the atomic structure of the L. pneumophila T4SS using cutting-edge single particle cryo-electron microscopy (cryo-EM) (Costa et al, Methods in Molecular Biology, 2017). The near-atomic details obtained from the 3D structure will provide unique insights into how toxins are recruited by the secretion system, how is the secretion system gated, and which is the toxins route within the secretion system. The project will pave the way for rational design of drugs that will abolish toxin secretion preventing bacterial survival and disease.
The project will provide training in the biochemical isolation and characterization of large membrane protein complexes, cutting-edge single particle cryo-EM data collection and processing (Costa et al, Cell, 2016). This work will take advantage of the state-of-the-art electron microscopy infrastructures located at the Francis Crick Institute and Diamond Light Source.