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Project

Investigation of the structure-function relationship of sporozoite 6Cys proteins from the malaria parasite Plasmodium vivax.

Malaria, caused by Plasmodium parasites, is one of the 'Big Three' infectious diseases, together with HIV and TB. Each year more than 200 million cases of the disease are documented, including more than half a million deaths (>65% of the deceased are children under the age of five). P. falciparum and P. vivax are the most widespread and notorious members infective to humans. Although P. vivax induces a milder form of the disease, severe cases are increasingly reported. In addition, P. vivax has a much larger geographic range compared to P. falciparum; while falciparum malaria predominantly burdens Sub-Saharan Africa, vivax malaria affects the lives of millions across Latin America and South-East Asia. Despite having a severe socio-economic impact on large parts of the world, the progress in battling P. vivax is slow. Problems are worsened due to low-efficacy vaccines, drug-resistant parasites and the (re-)emergence of the disease around the globe. This calls for active research into the biology of the malaria parasite. Productive invasion of a host liver cell by a form of the parasite called the sporozoite (SPZ) represents an essential event in the parasite's life cycle. Infectious SPZs express several 6Cys proteins on their surface (P36, P52, B9, P38 and P12p) and P36, P52 and B9 have been shown to be essential for productive SPZ invasion. Many aspects of the structure-function relationship of SPZ 6Cys proteins are unknown: i) studies on P. vivax P36, P52, and B9 are very limited, ii) the existence of a P. vivax P36-P52-B9 complex remains to be validated, iii) the molecular determinants and affinities of interactions within this complex are yet to be revealed, and iv) the molecular basis for SR-BI receptor recognition is enigmatic.This research project will aim to shed light on these relevant questions through an interdisciplinary research approach combining biophysical, structural, and functional assays. Given the knowledge gap in P. vivax biology and the general importance of SPZ 6Cys proteins in SPZ biology, tackling the above-mentioned questions is expected to generate many novel, relevant findings that may be used in the battle against malaria.
Date:1 Oct 2022 →  Today
Keywords:MALARIA, PROTEIN-LIGAND INTERACTIONS, HOST-PARASITE INTERACTIONS
Disciplines:Parasitology, Molecular biophysics, Adaptive immunology, Structural biology