Project Title: Genomic and transcriptional analysis of malaria parasites from controlled human malaria infection of Kenyan adults with varying exposure to malaria
Host Organisation: Kenya Medical Research Institute (KEMRI), Kenya
Falciparum malaria remains a major life-threatening disease in children aged under 5 years in sub Saharan Africa. Naturally acquired immunity to malaria develops after repeated exposure to malaria and can both limit parasite growth and prevent parasites from causing disease. This has a major impact, reducing severe forms of the disease associated with high parasite counts and increasing asymptomatic infections associated with low parasite counts. While this process is well-known, the parasite molecules that are targeted to generate immunity in adults are not - identifying them is crucial to finding long-term solutions to combat malaria. I have previously conducted population-level comparisons of falciparum parasites sampled from human populations with high levels of immunity versus human populations with low levels of immunity and found variation in P. falciparum gene regulation. Here I propose to use a recently established human malaria infection model in Kenya to investigate how the parasite gene expression pattern varies in the face of differing levels of human immunity. This system gives a unique opportunity to study these questions in a much more controlled manner, and I will use genomics and microarrays to characterize the changes that occur to the parasites genome and transcriptome in the face of varying host genetic and immune pressure during in vivo development. This will determine mechanisms of parasite adaptation to host immunity and identify parasite molecules with potential for vaccine development.