Transfection technologies for investigating the role and antimalarial potential of GPCR-like proteins in Plasmodium (360G-Wellcome-202094_Z_16_Z)

Malaria causes more than 650 000 deaths annually, and new antimalarial therapies are urgently needed. Signalling pathways acting through GPCRs are the targets of > 50% of drugs currently in therapeutic use, so have high potential as antimalarial drug targets. This project is aimed, therefore, at exploring the function and therapeutic potential of Plasmodium members of an evolutionary-ancient family of proteins, GPR89, that are classified as divergent G-Protein Coupled Receptors and have been implicated in environmental sensing in a diverse range of eukaryotes. We aim to investigate the role of Plasmodium GPR89 in the regulation of parasite growth, differentiation, virulence and immunogenicity, and gain insights into signaling pathways operating through GPR89 by identifying binding partners within the infected-erythrocyte. Our approach will take advantage of our unique expertise in transfection technologies for Plasmodium chabaudi; a particularly useful and relevant mouse model for studying acute and chronic malaria infection and for investigating host-parasite interactions that regulate cell-cycle progression, differentiation and immune evasion during blood-stage infection. These studies will advance our understanding of GPCR-like proteins in Plasmodium and will bring technological advances to the P.chabaudi model; so providing an experimental framework for the investigation and validation of a new class of therapeutic targets.