Identification of genomic components that predict transmission of the malaria parasite in different vector species (360G-Wellcome-220185_Z_20_Z)

The malaria parasite (Plasmodium falciparum) has a complex life cycle in which it must transit through multiple environments in a vertebrate host and mosquito vector. Transmission begins with ingestion of an infectious blood meal by one of 40 potential Anopheles mosquito species capable of transmitting the disease. This initiates the most extreme population bottleneck in the life cycle in which the parasite must rapidly undergo fertilisation, develop into an invasive form and transit through the midgut epithelium. The overarching goal of this proposal is to understand how this transmission through the mosquito vector drives selection on the parasite. I hypothesise that parasites have adapted to their local vector community composition, and this shapes their ability to infect sympatric and allopatric vector species. Using large- scale transmissibility assays and single-cell RNA-sequencing, I will identify genomic and transcriptomic vector-dependent signatures of transmission. I will then generate allelic-replacement parasites to unambiguously attribute phenotypic variation in species-specific transmission to specific loci in the parasite. Comprehensively understanding how vector communities shape parasite populations will guide future interventions and vector control programs by providing information that will allow for strategies to be locally tailored based on parasite genomic-surveillance and entomological surveys.