Dissecting changes in Plasmodium berghei gene expression at the initial stages of mosquito midgut transmission


K L Bloomer2; R Morton2; B M Mugambi3; D Beraldi1; K K Modrzynska1
1 Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, UK;  2 Institute of Infection, Immunity & Inflammation, University of Glasgow, UK;  3 Centre for Biotechnology and Bioinformatics, University of Nairobi, Kenya


Malaria is a devastating disease caused by unicellular protozoan parasites of the genus Plasmodium. These parasites have a complex lifecycle with >10 stages, transitioning between asexual replication within the mammalian host and sexual development within the midgut of a female Anopheles mosquito.  Passage from the mammal to mosquito as well as the hostile conditions within the insect midgut significantly reduce parasite numbers making targeting transmission at this stage appealing.  However, there is limited data on the temporal mechanics of gene regulation during parasite midgut development which hampers the advancement of control strategies against these stages.  To rectify this gap in the literature we have performed an RNA-seq time course of Plasmodium berghei (a rodent malaria model) during this transition. Samples from 8 time points were analysed to investigate how gene regulation varies temporally.  We show that changes in gene expression are already observed at the very initial stages of development and have identified clusters of co-regulated genes with unique expression patterns as well as enrichment for GO terms and sequence motifs.  Integration of these datasets with the existing genomic accessibility data and occupancy profiles of the key transcription factors involved will provide further insight into the gene regulatory networks during the initial mosquito midgut transmission stages.  Additionally, an understanding of the developmental transition within the mosquito midgut will potentially improve current culturing methods of ookinetes from Plasmodium species. 

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