Developing novel inhibitors of unconventional secretion based on Botulinum based therapeutics

Unconventional secretion is a fundamental cellular process which not only underpins normal physiology but is a key driver in chronic inflammation and cancer. At present we have a limited molecular and mechanistic understanding of this process. The aim of this project is to use Botulinum based molecules to elucidate the role of SNARE proteins in unconventional secretion. The knowledge generated from this project in the longer term will provide a platform for the development of novel inhibitors of this pathway.

Clostridial neurotoxins are produced by anaerobic bacteria such as Clostridium botulinum. Each toxin molecule has a highly conserved zinc-dependent protease domain that specifically cleaves SNARE proteins, a family of molecules required for intracellular trafficking and vesicle fusion. This project will make use of a library of novel toxin molecules to identify and characterise the role of SNARE proteins in the biogenesis and fusion of unconventional secretory carriers with the cell surface.