The health consequences of genetic variants that have been selected by malaria, with a particular focus on polymorphisms affecting the red blood cell

Almost half of the world's population lives under the threat of malaria and it killed more than 400,000 people in 2015. Efforts to develop a vaccine have been disappointing and new approaches to control and treat malaria are badly needed. The existence of human genetic variants that provide natural protection against malaria has been recognised for more than 60 years. By studying such genes we stand to learn more about malaria and perhaps discover new ways to treat it. 

I will focus on four genes for which we have strong evidence of natural protection against malaria. All affect the red blood cell, the natural target of human infections. I will document their impact on malaria and other diseases through population studies in Kenya and observe their effects on rates of disease progression in adult volunteers who will be inoculated experimentally with live malaria parasites. I  will also study how they affect red cell function and investigate parasite invasion in the laboratory. 

By pinpointing the precise mechanisms for malaria resistance afforded by these genes we may be able to use them as a basis for drug and vaccine development.