Case Study

Geoffrey Masuyer , PhD

Structure and function of bacterial toxins

Research in the Masuyer lab focuses on the structure and function of bacterial toxins, particularly the mechanisms by which they interact with their host receptors, and the development of toxin-based therapeutics. Previous projects include the study of botulinum neurotoxins interaction with their human receptors using a biophysical approach, including X-ray crystallography. This led to the design of new molecules with improved receptor-recognition and enhanced clinical properties for the treatment of neuromuscular disorders.

Current projects centre on ADP-ribosyltransferase exotoxins, a group of potent bacterial virulence factors that include Pseudomonas exotoxin A and Cholix. They target essential intracellular pathways of their eukaryotic host by modifying key proteins through addition of ADP-ribose, leading to protein synthesis inhibition and cell death. These toxins are able to cross epithelial barriers of the lung or intestine, to reach their target cells. Their modular architecture makes them ideal molecules for protein engineering to retarget specific toxin functions into beneficial uses, such as immunotoxins or biological drug transporters. Our structural studies help us understand the molecular mechanisms underpinning the natural functions of this family of bacterial toxins in order to develop a new generation of toxin-based therapeutics, and design more efficient and safer molecules that will address current clinical concerns.