I will investigate what mediates an effective human immune response to infection with Plasmodium falciparum malaria.

I will approach this through studying the Fulani ethnic group of West Africa, who are relatively resistant to malaria infection. The basis of the Fulani protection from malaria has never been established. However, we have performed a pilot study which suggests that reduced levels of adenosine-to-inosine (A-to-I) editing of RNA by ADAR1 following P. falciparum infection can drive a more effective innate immune response in the Fulani.

We have an established collaboration with the Malaria Research and Training Centre at University of Sciences Technique and Technology in Mali, who have strong ties to the Fulani community. At Stockholm University, I have had the opportunity to develop a strong background in immunology research techniques, specifically utilizing in vitro models of malaria infection in human monocytes, in the research group of Eva Sverremark-Ekström. As the role of RNA modifications is an emerging field, I plan to move to CEITEC, Czech Republic, to work with Mary O’Connell, who has pioneered the role of A-to-I RNA modification in the innate immune response to RNA.

Specifically, we will test the hypothesis that reduced rates of A-to-I editing of RNA in the Fulani following infection enables them to mount a more effective innate immune response to P. falciparum malaria, and contributes to their relative protection from the disease. Further, targeting of ADAR1 and/or reduction in levels of A-to-I RNA levels may present a novel strategy to boost effective immune response to malaria.

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