Probing Plasmodium Falciparum Glycosylation and Related Metabolic Pathways to Devise New Tools against Malaria (GlycoTools)

Glycosylation represents one of the most common and heterogeneous post-translational modifications of proteins, and complex glycoconjugates are involved in almost every biological process. Because of this glycoconjugates play major roles in nearly every human disease. P. falciparum conserves and expresses an active and distinct glycosylation machinery that only in last few years has begun to be unraveled. Thus, it was recently demonstrated that Plasmodium parasites express α-galactose-terminated glycans, not present in the human glycome, at their surface, and that anti-α-gal antibody responses in humans are protective against malaria. The nature and the exact structure of parasite α-galactose glycans remains uncharacterized, but preliminary works clearly reveal the presence of these glycoconjugates in specific form of the asexual blood stages of the parasite.

The glucosamine-phosphate N-acetyltransferase enzyme belongs to a gene family with a single and independent evolutive origin in the Apicomplexa phylum, more than 800 million years ago. Its significance for glycoconjugate metabolism in the malaria parasite, together with the unique sequence features of this gene family, highlights its importance as a potential selective drug target.

Project Details

Basic Science
Drug-based Strategies

Jun 2020 — Dec 2023

$214,919

Spain