Unravelling the host response to malaria infectionGAÉTAN BURGIO (ANU) in partnership with Frank Mockenhaupt (Charité) and Emanuel Heitlinger (HUB)Resistance of the parasite to antimalarial drugs is a growing concern and affects millions of patients worldwide every year. There is an urgent need to find novel treatment to improve the care of people as the parasite is becoming resistant to all existing antimalarials. In the general population, there are individual differences between humans that give some people an advantage in their ability to resist severe disease caused by the malaria infections [1]. This project aims to understand why these people are resistant to pathogens using mouse as a model. Cutting-edge genetic technologies (next-generation sequencing, CRISPR/Cas9) will be used combined with advanced mouse crosses to study the biology of the interactions between the host and the parasite.The Burgio lab has undertaken a large-scale ENU mutagenesis screen in mice. Mice carrying protective mutations survived a malarial challenge whereas all other mice succumbed. To date the lab has screened 15,000 G1 animals for both erythrocytic abnormalities and the ability to survive to the rodent parasite challenges. The group has identified and established 90 lines that are resistant to malaria and/or show erythrocyte abnormalities [2]. They have identified 42 causative sequence variants. They have developed a pipeline of biological assays to study the host response to infection. Using these assays, the group has described novel mechanisms of malaria susceptibility in mice [3]. The group also translates these finding in human malaria infection using blood from patients carrying hereditary haematological disorders.

 

Interlinkages: Florian Kurth (Charité), Alyssa Ingmundson (HUB)

 

References:(1) Lelliott, P.M. et al. (2015) Malaria J. 14: 289(2) Bauer, D.C. et al. (2015) BMC Genom. 16: 866(3) Greth, A. et al. (2012) PLoS One 7:e38999