ADELINE GOULET’S GROUP

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.

Phages revenge: structural and functional analyses of anti-CRISPR-Cas9 proteins. 

The AcrIIA6 Binding Mode to St1Cas9 Surveillance Complex Revealed by Cryo-EM

The endless battle for survival between phages and their prey drives an evolutionary arms race with a co-adaptation of their attack and defense mechanisms. Phages have evolved anti-CRISPR proteins (Acrs) to neutralize bacterial CRISPR-Cas immune systems. The striking sequence diversity of Acrs and the lack of homology to proteins of known function raise intriguing questions, particularly relating to their modes of action and their roles on the evolution of CRISPR-Cas systems.

In order to understand how Acrs work, we seek to unravel the molecular mechanisms of Acrs inhibiting CRISPR-Cas9. This will not only broaden our fundamental knowledge of phage-bacteria interactions but also certainly provide crucial tools to regulate CRISPR-Cas9-based genome edition in biomedical fields and therapeutics.

Dissecting the infection mechanisms of siphophages infecting Gram-positive bacteria. 

Reconstruction of the p2 phage in the “resting” and “activated” forms

Siphophages, members of the Siphoviridae tailed phages family and the most abundant bacterial viruses on Earth, play important roles in controlling bacterial populations in every living ecosystem. Most of them use their non-contractile tail to bind to sugars at the surface of Gram-positive bacteria. Yet, several aspects of their biology remain remarkably elusive. Our aim is to unravel the molecular mechanisms used by such siphophages to 1) bind to their host, 2) overcome the host cell envelope barrier to deliver their genome, and 3) create a favorable environment for their proliferation inside the host. This will generate a deep understanding of the molecular details of phage infection, which is essential for decoding phage biology as well as for developing tools for therapeutic and biocontrol purposes.