Last Updated: 13/03/2025
Determining how P. falciparum survives fever with an aggregation-prone proteome
Objectives
This project will explore whether asparagine-repeats in P. falciparum proteins are functional during fever by studying two proteins with such repeats: GCN5 and CAF1. This project will attempt to rescue GCN5/CAF1 knockdown/knockout lines with different constructs lacking asparagine-repeats. Some of these constructs will involve orthologs from other Plasmodium species to circumvent potential pitfalls that come with truncated proteins.
Plasmodium falciparum is the causative agent of malaria in humans, a devastating blood infection that remains a leading cause of morbidity and mortality. Although complications can result in endothelial leakage and perturbation of the blood brain barrier, the hallmark of this disease is recurrent fever episodes. Almost 25% of the P. falciparum proteome contains asparagine repeats of 37 consecutive residues on average. Given that proteins with asparagine-rich domains are well known to aggregate particularly during heat stress, it has been a long-standing question in the field how P. falciparum survives fever. Interestingly, similar domains have been found to increase survival of the cell by targeting proteins to specific organelles for protection during stress. Rubiano Cardona will also determine the interacting partners and follow the fate of these proteins during heat stress and will observe how constructs lacking asparagine-repeats affect these dynamics. She is confident that the proposed work will elucidate the molecular mechanisms that protect the parasite during fever and will help us to develop new antimalarial strategies against this parasite.
Jul 2023 — Jun 2025
$65,106
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