Last Updated: 29/09/2025
Functional proteome landscape of malaria parasite during the life cycle in host and vector
Objectives
The main aim of this study is to characterize functional proteome states during malaria parasite sexual development in the host and the vector by leveraging two recently developed, powerful proteomic approaches, Thermal Proteome Profiling (TPP) and Limited Proteolysis Mass Spectrometry (Lip-MS).
Walter and Eliza Hall Institute of Medical Research (WEHI), Australia
To achieve the ultimate goal of malaria elimination, a new generation of antimalarial therapeutics is required that have both transmission-blocking and chemoprotective properties. However, to facilitate the rational design of multi-stage targeting antimalarial drugs, it is first necessary to bridge knowledge gaps in the understanding of malaria parasite transmission to mosquitoes and its development at the host-vector interface. TPP and Lip-MS allow proteome-wide readout of protein stability, which is influenced by protein interactions with diverse physiological ligands, metabolites, cofactors, DNA/RNA, posttranslational modifications, and protein complex formation. Consequently, protein stability serves as a proxy for its functional state in a living cell. Monitoring stability dynamics can inform on the functional states of transcription factors, protein-protein interactions, and enzyme activity. Datasets generated by this study will answer fundamental biological questions on proteome regulation during parasite development and the molecular events governing transmission. To characterise essential molecular processes, the study will monitor the effect of transmission-blocking agents on proteome stability, identifying their targets and the pathways they disrupt. This project will not only develop a new understanding of malaria biology but will also identify novel avenues for the rational design of antimalarial interventions.
May 2022 — Apr 2025
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