Gene expression regulation during the early ookinete development – maternal and paternal genome contribution.

New malaria control measures are urgently needed and their development requires a better understanding of the complex life cycle of the disease agent – a protozoan parasite from Plasmodium genus. The biggest bottleneck of this cycle takes place during the initial stages of obligatory mosquito transmission when Plasmodium gametocytes fertilise and create motile ookinete forms, able to penetrate the insect midgut. This transition requires major modification of the parasite’s transcriptome but the molecular mechanisms regulating this process are still very poorly understood. Their investigation is further complicated by the fact that Plasmodium zygote contains two parental genomes and both mono- and bi-allelic expression has been observed during the ookinete development.  Investigations were started on the parasite’s transcriptome during the ookinete formation and the role of key transcription factors and chromatin accessibility in this process. Now it is proposed to analyse the sex-specific allele expression at this stage, using both rodent and human malaria models, and the combination of genetic crosses, single-cell sequencing and conditional mutagenesis. This will add an additional dimension to the datasets already produced and generate a comprehensive model of the gene expression changes at the ookinete stage.

Enabling Technologies & Assays
Genetics and Genomics

Sep 2022 — Sep 2025

$711,254

United Kingdom