Bacteria are unicellular free living organisms.  Most of them recycle the organic matter but a small proportion of them can cause infectious diseases.  These pathogenic bacteria have evolved a variety of mechanisms which allow them to escape the immune defenses of the host.  Probably the most sophisticated of these mechanisms consists in injecting proteins straight into the cells of the immune system. These proteins are "effectors" which disarm or reprogram the host target cells by sabotaging or hijacking the cellular signalling network. Their injection into host cells, involves a kind of nanoseringe built at the surface of the pathogenic bacterium.  Such a nanomachine, called an "injectisome" is found in a wide variety of pathogenic bacteria, including Yersinia pestis, the agent of plague but also Salmonella a common agent of gastroenteritis and Pseudomonas aeruginosa an opportunistic pathogen affecting burned, immuno compromized and cystic fibrosis patients. The injectisome is one of the most complex bacterial nanomachines known. It consists of a transmembrane basal body and a ca 60-nm long needle protruding from the surface.  Injectisomes are potential targets for drugs designed to treat infections by antibiotic-resistant bacteria and parts of injectisomes have been shown to be good vaccines to prevent infections.

In addition, they represent a remarkable model of bio nanomachines and their understanding represents a challenge for molecular biologists.  This project focuses on the injectisome of Yersinia and the goal is to decipher its structure at atomic level, a pre-requisite for the understanding of the molecular mode of action. This structure determination is a challenge at the forefront of the technology. It requires the combined expertise of molecular biologists, electron microscopists, crystallographers and computational biologists, each of them developing new tools and algorithms.  The project thus addresses a complex molecular biology problem with medical implications but it is also expected to lead to innovative technology developments.