Dr Alfred Ngwa
My research team applies in vitro cell assays and analysis of genomic variation to determine response of the major malaria parasite Plasmodium falciparum to changes in its environment including response to drugs and transmission. We explore genetic variation in parasite, human and vector populations across Africa that may determine variance in outcome of exposure and infection with Plasmodium species.
I teach a practical module with Prof David Conway in the MSc in Pathogen Genomics
My main interest is to understand how malaria parasite populations adapt to changes in the environment brought about by various interventions targeting parasite and the vector populations as well as natural processes in the host such as immunity. I work within the malaria research programme at MRC, The Gambia to employ targeted and whole genome sequencing of selected malaria endemic populations. Some more specific interests are in the following areas;
• Determining the relationship between invasion, virulence and drug susceptibility phenotypes and specific mutations in the genome of Plasmodium falciparum.
o We seek to understand the co-evolution of parasite and host genes as a step towards the selection of the immunogenic candidate genes for vaccine development. We have so far focused on genes showing signatures of balancing selection assumed to be a consequence of immune selection. However, several surface genes of both immune cells and erythrocytes show signs of balancing selection. Hence balancing selection in the pathogen could be a co-evolutionary process needing further studies. I will like to apply this thesis to other pathogens such as helminths that are co-endemic with malaria in developing countries.
o We track the accumulation of mutations that confer adaptation to drug intervention pressure from whole genome and targeted sequencing of retrospective samples collected over the quarter of a century. We hypothesise that drug resistance becomes more effective following successive accumulation of mutations contributing to the development of the phenotype.
o We believe variance in transmission can be determined from the micro-ecology of parasite in endemic populations. This natural variance can be perturbed by interventions that disrupt natural population structure and allow for selection of fit ‘strains’. With intensive cover of intervention such selection allows for the expansion of such strains creating hotspots of transmission in generally low endemic areas. We use genetic tools to determine and tract dynamics in such hotspots. We map the flow of isolates across The Gambia and Africa using identity-by-decent and other pairwise genetic similarity matrices.
• In am interested in developing technical alternatives and methods to locally analyse both SNP and structural variations on the Plasmodium genome. For example employing various alignment algorithms to optimise the calling of microsatellite and indel variants from next generation sequencing short reads. We believe that the more rapid evolution of STR variants will enable early determination of regions in the genome that may be under directional selection from new chemotherapeutic interventions.
• We wish to develop non-expert tools for analysis of population genetic data to uncover patterns in rarely accessed populations. The exploration of genetic data especially those generated from NGS analysis has been limited by the need for computer programming and quantitative skills that are mostly deficient in pathogen endemic communities. Development of a combination of low-spec computers and softwares for easy manipulation of genetic variables will broaden our understanding of many more parasite populations as it will rapidly integrate local researchers into population genetic research.