Host-Pathogen Interaction

The studies we conduct focus on one hand on factors of pathogenicity of bacteria and on the other hand on means of response of host organisms. Our projects can be grouped in 2 scientific disciplines which are immunology and microbiology. 

At the methodological level, X-ray crystallography will remain the basis of all our studies but we are aware of the current developments in the field of structural biology. In particular, the rise of electron microscopy is opening up new avenues. We are also running a camelid antibody generation platform (also called VHH or Nanobody). This tool gives us a significant competitive advantage in tackling most of our projects.

Bacteriophages (phages) are the most abundant biological entities on Earth. Yet, these sophisticated bacteria-killing nanomachines remain poorly understood. What has made them so successful?

Our main research interest is, in a pan-phage approach, to unravel the molecular mechanisms deployed by phages upon infection to recognize, puncture, and hijack their host. We use a multi-disciplinary approach including cryo-electron microscopy, X-ray crystallography, and biochemical/biophysical characterization of macromolecular interactions. With these combined investigations we aim to obtain multi-scale information on phage infection modus operandi. This provides us with a comprehensive understanding of phage-bacteria interactions, but not only that, as this knowledge will pave the way towards rational development of phage-based applications for therapeutic, diagnostic and biocontrol purposes.

Type IX Secretion System (T9SS)

The T9SS is responsible for Porphyromonas gingivalis pathogenesis through secretion of virulence factors, and for Flavobacterium johnsoniae motility through secretion of adhesins. Among the 18 identified proteins that are involved in T9SS function, the K-L-M-N proteins are supposed to form the core complex. We propose that the outer membrane ring-shaped K-N complex serves as an interaction platform to recruit the inner membrane L-M complex, and that the L-M complex is a novel rotary motor driven by proton motive force. Our objective is to solve the structures of the isolated soluble domains of L and N proteins, and of the L-M and K-L-M-N membrane complexes from the two bacterial models, by X-ray crystallography and cryo-EM (in collaboration with Olivier Lambert, ICBMN, Bordeaux). The function of the L-M complex, and notably its role as a rotary motor, will be addressed by in vivo approaches (in collaboration with Eric Cascales, LISM, Marseille).