Last Updated: 27/05/2025
Single Cell Genomics for Malaria Parasites
Objectives
This study applies novel approaches which generate whole genome sequence from single parasite-infected cells. The research team will apply these to human infections to refine our understanding of the complexity of malaria infections.
These new methods will be exploited: (1) to dissect the composition of P. falciparum infections in a region of intense transmission. These data will be used to determine how many independent genotypes are present, the relationships between the component haplotypes and their relative abundance within infections, and to critically evaluate the performance of indirect methods currently employed.
Multiple genotype and multi-species infections of malaria (and other pathogens) are extremely common. For example >80% of human P. falciparum infections in sub-Saharan Africa contain multiple parasite genotypes. Most malaria species cannot be cultured in the laboratory, precluding culture based isolation of individual clones. Currently, genetic analysis of such complex infections involves either characterization of hypervariable genome regions or more recently, deep sequencing of infections. Both methods are inadequate because parasite haplotypes cannot be constructed and statistical methods for resolving complex haplotype mixtures are not yet available.
To resolve this problem, robust methods for single-cell genomics of Plasmodium have been developed, utilizing FACs to isolates single infected cells, followed by whole genome amplification, and genetic characterization and/or deep sequencing. These methods open up new opportunities for understanding the composition of complex malaria infections, for validating statistical methods that seek to reconstruct haplotypes from deep sequence data, and to examine the within host-dynamics of non-culturable malaria infections.
Dec 2014 — Nov 2019
$1.83M
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