Towards understanding of cell death induced by Pseudomonas cyclic lipopeptides in cancer cells

Rosseel Eline , 2022
The research in this thesis is conducted as part of the MEMCLIP consortium at Ghent University, which consists of chemists and biologists. The overall goal of this project is to lay an experimental foundation for understanding the mode of action by which natural products: Pseudomonas cyclic lipopeptides (CLiPs), or derived synthetic variants act on cancer cells. These CLiPs show different interesting properties of potential use in medicine, such as activities against bacteria, fungi, viruses and, what we are interested in, possible anticancer effects. In the first section of this thesis we probed the capacity of various CLiPs to kill cancer cells using model cancer cell lines. For the second part, we exploited three chemically synthesized fluorescent variants of viscosin (a Pseudomonas CLiP). These modified CLiPs had comparable biological activity in an assay measuring cell death. For the first time, we were able to visualize the CLiP-membrane interaction with confocal microscopy. These fluo-CLiPs are promising tools to further unravel the mechanism of action of CLiPs on mammalian cancer cells. The long term goal of this research on Pseudomonas CLiPs is to investigate their potential as anticancer drugs. The high number of cancer cases worldwide and the limitations bound to existing therapies suggest an urge to explore new cancer strategies.

Promotor Christophe Ampe
Opleiding Biomedische Wetenschappen