My group concentrates on elucidating the biosynthesis and function of specific carbohydrates in eukaryotic pathogens to identify new drug targets. Attractive targets are then analysed in collaboration with specialists for the development of lead compounds.
Pathogens are surrounded either by a cell wall or a dense glycocalix extremely rich in carbohydrates. This cell coat protects the pathogen from its environment and enables interaction with its host. Therefore its integrity is often crucial for the organism survival or for the establishment of infection and many of the medicines currently in use act by interfering with the cell coat assembly.
The parasites Leishmania, responsible for human diseases collectively called leishmaniases and the opportunistic fungus Aspergillus fumigatus, the agent of invasive aspergillosis (a leading cause of infectious death in modern hospitals), are our principal model organisms. The existing drugs against these organisms often pose problems of toxicity and the occurrence of therapeutic failures is frequent. The development of new drugs is needed and would clearly benefit from a deeper knowledge of the glycosylation pathways of these pathogens.
Unique proteins involved in glycan biosynthesis in parasites and fungal pathogens are the primary focus of our researches. These include proteins involved in the biosynthesis and transport of nucleotide sugars as well as enzymes responsible for glycan assembly. Our projects aim at:
- Identifying and characterising new glycosylation pathways (ideally absent in human)
- Analysing their importance for the pathogen survival, growth or virulence (in mice models) to identify potential drug targets
- Analysing attractive targets and exploiting this information for development of lead compounds (in collaboration with specialist).
Methods commonly used include genetic manipulation of pathogens (e.g. gene disruption, conditional regulation of gene expression, protein destabilisation), analysis of glycans (e.g. N-glycans, glycolipids, polysaccharides), protein expression and purification and in vitro enzymatic assays.