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Investigating host-pathogen genetic interactions in malaria cases around Lake Victoria, Kenya - NU/LSHTM Project

Title of PhD project / theme

Investigating host-pathogen genetic interactions in malaria cases around Lake Victoria, Kenya

Supervisory team

Dr. Susana Campino (LSHTM, Lead, Susana.Campino@lshtm.ac.uk),

Professor Kiyoshi Kita (NU, kitak@nagasaki-u.ac.jp

Professor Taane Clark (LSHTM, Taane.Clark@LSHTM.ac.uk),

Professor Akira Kaneko (Inst. for Tropical Medicine)

Brief description of project / theme

Malaria, a mosquito-borne disease caused by Plasmodium parasites, is an important public health problem causing an estimated >200 million cases and >400,000 deaths annually. The majority of malaria cases and deaths occur in sub-Saharan Africa, including in Kenya. To assist the task of malaria elimination, it is crucial to improve our understanding of the host and parasite genetic factors associated with severe and asymptomatic malaria. Significant selection pressure has been exerted on the genomes of human populations exposed to Plasmodium falciparum infection, resulting in the acquisition of mechanisms of resistance against severe malarial disease. Many host genetic factors, including sickle cell trait and glucose-6-phosphate dehydrogenase (G6PD) deficiency, have been associated with reduced risk of developing severe malaria, but do not account for all of the observed phenotypic variation [1]. In this project we will collect blood samples from severe and asymptomatic individuals around Lake Victoria, and characterise the host genomes using genome-wide SNP chips, as well as the parasite genomes using whole genome sequencing. We will assess the genetic diversity in known malaria host susceptibility genes (e.g. G6PD), as well as identify alleles associated with clinical phenotypes, including through the application of GWAS and population genetic selection approaches [1]. The population structure of both host and parasites will be inferred [1,2], and a genome-to-genome analysis performed to identify host-pathogen genetic interactions. This work could provide insights into the biology underlying malaria disease; such insights could inform the process of drug discovery, inform the development of tools for rapid diagnosis, surveillance and evaluation of malaria control interventions. The outputs of this work will inform disease control measures and policy.

[1] Ravenhall M, Campino S, …, Clark TG. Novel genetic polymorphisms associated with severe malaria and under selective pressure in North-eastern Tanzania. PLoS Genet. 2018 Jan 30;14(1):e1007172.

[2] Ravenhall M, …, Campino S, Clark TG. An analysis of large structural variation in global Plasmodium falciparum isolates identifies a novel duplication of the chloroquine resistance associated gene. Sci Rep. 2019 Jun 4;9(1):8287.

The role of LSHTM and NU in this collaborative project

NU runs field studies around Lake Victoria, and routinely collects samples for genomic characterisation. The LSHTM has expertise in high throughput DNA genotyping and sequencing, and data analysis (e.g. GWAS). NU has expertise in functional studies to follow-up any interesting biological insights.

Particular prior educational requirements for a student undertaking this project

A background in molecular biology, parasitology or another related area; an interest in genomics and sequence data analysis.

Skills we expect a student to develop/acquire whilst pursuing this project

Bioinformatics, population genetics, whole genome sequencing, advanced molecular biology skills, and genomic epidemiology, GWAS