IDENTIFYING HOST-PATHOGEN INTERACTIONS WHICH CAUSE SEVERE MALARIA

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Infectious diseases continuously challenge the body's defenses. Perhaps surprisingly, we know rather little about how many infections actually cause serious illness. Often we can't explain why the same infection causes mild illness in one person but kills another. Finding out why this happens is key to finding better treatments.Malaria is one infection we need to understand better. It is a disease caused by tiny parasites within red blood cells which are spread from person to person by the bite of mosquitoes. Malaria infects more than 200 million people every year around the world and kills almost 1 million of them. Some features linked to severe infections have been identified, but we don't really know how these lead to severe illness and death.This research aims to explain how interactions between the body's defenses and the malaria parasite result in differences in the severity of illness. We aim to use a new technique to do this. We will look at all the genes that are simultaneously active in the malaria parasite and the human cells in the blood, to find patterns associated with severe illness. Malaria is an ideal disease to assess with our new technique because all of the parasites live in the blood. This research will help to identify new approaches to the treatment of severe malaria. This could save many lives in the future. If we are successful, we think the approach could also be applied to many other infectious diseases. This research will be carried out by collaborating scientists at Imperial College London, The London School of Hygiene and Tropical Medicine, University of Queensland (Australia), National Institutes of Health (USA) and MRC Laboratories, The Gambia. It draws together world leaders in malaria research, genetics, computing methods and statistics. The research will use stored samples collected from Gambian children with malaria. Some of these children had a mild illness, and some had life-threatening complications. The activity of all the human and parasite genes will be measured with a technique called "RNA Sequencing". A series of advanced computer techniques will be used to find the patterns of gene activity associated with severity of malaria. Once we have identified the patterns associated with severe malaria we will test them in the laboratory to see if we can target them to prevent severe malaria. We do this by deliberately altering genes, or by adding or blocking molecules that are important in generating the patterns we identify. This allows us to be sure our findings are causal, rather than just chance associations. The raw data and all our findings will be made publically available, so that other scientists can use the data to answer other important questions about malaria.