MRC Human Immunology Unit
MRC Weatherall Institute of Molecular Medicine
Emeritus Professor of Tropical Medicine
Infection by Plasmodium falciparum causes 1-2 million childhood deaths per annum in Sub-Saharan Africa alone. This virulence is due to a high rate of multiplication and the alteration of the host erythrocyte membrane.
Some parasite proteins, encoded by large variant multigene families, are inserted into the membrane and are accessible from the exterior. Parasitised red cells then concentrate in various organs and cause damage by binding to endothelial cells, to other red cells forming rosettes which may reduce blood flow, or to dendritic cells inhibiting their activation. Switching between different members of the multi-gene families allows the parasite to evade the protective antibody response.
Our group seeks to study the molecular basis for adherence related pathogenesis, antigenic variation and immunity through:
- Identification of host receptors involved and the role of binding to individual receptors in severe disease.
- Understanding these interactions at the molecular level.
- Understanding the role of different parasite multi-gene families in adhesion and identifying binding sites.
- Determining how antigenic variation is controlled at the molecular level.
- Determining how the natural immune response evolves to these variant proteins and understanding the role of epitope specific antibody responses in protection.
- Understanding how parasites proteins become exported through the cytoplasm of a cell that has no protein trafficking machinery.
We have taken a multidisciplinary approach involving biochemical, immunochemical, genetic, cell biological and population based studies. We were one of the initiators and significant contributors to the malaria genome project that is now nearing completion.
Individual-level variations in malaria susceptibility and acquisition of clinical protection
Valletta JJ. et al, (2021)
Author Correction: Genomes of all known members of a Plasmodium subgenus reveal paths to virulent human malaria.
Otto TD. et al, (2020), Nat Microbiol, 5
Genomic and transcriptomic evidence for descent from Plasmodium and loss of blood schizogony in Hepatocystis parasites from naturally infected red colobus monkeys.
Aunin E. et al, (2020), PLoS Pathog, 16
Genomic and transcriptomic evidence for descent from Plasmodium and loss of blood schizogony in Hepatocystis parasites from naturally infected red colobus monkeys
Aunin E. et al, (2019)
Evolutionary analysis of the most polymorphic gene family in falciparum malaria
Otto T. et al, (2019)