Matthias Vanheede

CV

Matthias Vanheede obtained his Master of Science in Chemistry summa cum laude in 2023, for which he was awarded the Dow Benelux Excellence in Science Award 2023. He did his master dissertation in the OBCR group (under supervision of Prof. Dr. Annemieke Madder and Prof. Dr. José C. Martins), dedicated to the design and synthesis of imaging probes for cellular localization of cyclic lipodepsipeptides (CLiPs).

After graduating, he returned to the OBCR group to start his PhD. His research is focussed on a combined structure-activity and biophysical investigation of the cyclic lipopeptide tolaasin, the virulence factor causing brown blotch disease on mushrooms. Key areas of the work include building block synthesis, peptide synthesis and bioactivity assays.

Research Project

A combined structure-activity and biophysical investigation of the cyclic lipopeptide tolaasin, the virulence factor causing brown blotch disease

Tolaasin, an 18 residue cyclic lipopeptide, is the main virulence factor of Pseudomonas tolaasii, and causes brown blotch disease in edible mushrooms. In addition to this antifungal activity, this secondary metabolite also displays activity against Gram-positive, Gram-negative bacteria and cytotoxicity against MDA-MB-231 cancer cells. This broad cell targeting activity is attributed to its membranolytic properties.

While experimental data supports direct interaction with cellular membranes, molecular level understanding of the features and underlying mechanisms of tolaasin activity, ultimately leading to cell lysis, are not well understood.

In this PhD, a total synthesis route for tolaasin will be developed, followed by combined and comparative biological and biophysical evaluation of a series of specifically designed analogues. Of note, monitoring of leakage events and kinetics using ps-time-resolved fluorescence spectroscopy will provide unprecedented insight in the nature of tolaasin-induced membrane perturbation, thus providing fundamental, molecular level understanding of the underlying mode of action.