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Last Updated: 06/03/2025
An investigation into the mechanisms of Plasmodium vivax chloroquine resistance (PvCQR): a transcriptome/transgenic approach
Objectives
*Original title in Dutch: Een onderzoek naar de mechanismen van Plasmodium vivax chloroquine-resistentie (PvCQR): een transcriptoom/transgene benadering
This project will capitalize on a large collection of existing P. vivax clinical samples (also with CQR) at the Malariology Unit to pioneer in the application of cutting-edge RNA sequencing technologies, including single-cell transcriptomics which will help unravel the transcriptional network of genes underlying PvCQR, and the impact of infection complexity (parasite life-stages and mixed clones present in natural infections) in treatment outcome.
Plasmodium vivax is the most predominant species outside Africa, and many countries aiming towards malaria elimination by 2030 are seeing an increase in resistance against chloroquine. The markers and mechanism of chloroquine resistance (CQR) remain unknown; hampering molecular surveillance and accurate diagnosis of CQR. The hypothesis, based on results from a clinical study in Vietnam and recent published data obtained from parasites adapted to a non-human primate model, suggest that altered gene expression of transporter genes plays a major role in PvCQR. P. knowlesi transgenic lines, differentially expressing P. vivax genes, are generated using advanced CRISPR-Cas9 genome editing strategies, in order to determine underlying drug resistance mechanism. Outcomes of the study will directly benefit P. vivax patients and drug resistance surveillance, while advancing research with new protocols, tools, datasets and transgenic lines to investigate P. vivax biology.
Nov 2021 — Dec 2026
$733,600
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