Bacteria were long thought to be "bags of enzymes", lacking the organisation and complexity of Eukaryotic cells. However, in the past few decades, it has become apparent that they in fact possess a very intricate network of macromolecular assemblies, that regulate their metabolism, cellular replication, and interaction with their surrounding environment. We use cryo-electron microscopy (Cryo-EM), combined with other structural, biophysical and protein engineering methods, to decipher the structure of such bacterial assemblies, to determine their mechanism of action, and the molecular basis for their assembly, towards therapeutic and/or biotechnology applications. I will present some of our recent results on two such bacterial macromolecular assemblies: the MLA system, involved in lipid trafficking across membranes in gram-negative bacteria, and responsible for broad-range antibiotic resistance; and the bacterial cytoskeleton, a network of filament-forming proteins involved in localising proteins and DNA within the bacterial cell. Notably, I will show how our use of cryo-EM, combined with AI-driven approaches, allows us to exploit these structures to develop new antibacterial drugs, and to engineer new biomaterials for therapeutic applications.
I was born and raised in Paris, France. I moved to London for my University studies, leading to a degree in Molecular Biology, followed by a Masters in Structural Biology, from Imperial College London. I then did my PhD in biophysics at King’s College London, where I used Nuclear Magnetic Resonance to elucidate the molecular mechanism of proteasome hijacking by the HIV protein VIF. Following this, I took a post-doc position at the University of British Columbia (Vancouver, Canada), where I used X-ray crystallography to decipher the structure of the type III secretion system, a syringe-shaped macromolecular assembly responsible for the injection of toxins into host cells found in many bacterial pathogens. Then in 2015, as it became apparent that cryo-EM was fast-becoming the leading method in structural biology, I joined the group of Justin Kollman at the University of Washington (Seattle, US), where I employed this technique to elucidate the structure of bacterial cytoskeleton proteins. In 2017, I moved back to the UK, specifically to the university of Sheffield, to start my group. We relocated to King’s College London in February 2020, at the cusp of the COVID pandemic. I am also the co-founder and CEO of PROSEMBLE LTD, a biotech company aiming at exploiting bacterial complexes to design nanoparticles towards the targeted delivery of anticancer drugs.