2020 Fiscal Year Research-status Report
Identifying malaria vaccine candidate antigens using genetic linkage analyses
Project/Area Number |
19K07526
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Research Institution | Ehime University |
Principal Investigator |
カレトン リチャード 愛媛大学, プロテオサイエンスセンター, 教授 (10503782)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | Plasmodium vinckei |
Outline of Annual Research Achievements |
We have generated a comprehensive genetic resource for P. vinckei comprising of five reference-quality genomes, one for each of its subspecies, blood-stage RNA sequencing data for five P. vinckei isolates, and genotypes and growth phenotypes for ten isolates. Additionally, we sequenced seven isolates of the RMP species Plasmodium chabaudi and Plasmodium yoelii, thus extending genotypic information for four additional subspecies enabling a re-evaluation of the genotypic diversity and evolutionary history of RMPs.
The five subspecies of P. vinckei have diverged widely from their common ancestor and have undergone large-scale genome rearrangements. Comparing P. vinckei genotypes reveals region-specific selection pressures particularly on genes involved in mosquito transmission. Using phylogenetic analyses, we show that RMP multigene families have evolved differently across the vinckei and berghei groups of RMPs and that family-specific expansions in P. chabaudi and P. vinckei occurred in the common vinckei group ancestor prior to speciation. The erythrocyte membrane antigen 1 and fam-c families in particular show considerable expansions among the lowland forest-dwelling P. vinckei parasites. The subspecies from the highland forests of Katanga, P. v. vinckei, has a uniquely smaller genome, a reduced multigene family repertoire and is also amenable to transfection making it an ideal parasite for reverse genetics. We also show that P. vinckei parasites are amenable to genetic crosses
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Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
I have now completed the genomic, phenotypic and transcriptomic characterisation of many new strains of P. vinckei, used them to compile a new and definitive rodent malaria phylogeny, and made these available to the malaria research community. I have published this work in the prestigious BMC Biology journal
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Strategy for Future Research Activity |
I now intend to characterise further strains of P. vinckei and optimise their transmission to mosquitoes in order to conduct genetic crosses.
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Causes of Carryover |
Next year's budget will be spent on publication fees, plastic consumables, insectary maintenance, molecular biological reagents, and mice.
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