Research Fellows Directory
Dr Hussein Abkallo
University of Edinburgh
Genetic validation of the function of PfEMP1 in Plasmodium falciparum rosette formation
The most severe pathological outcome of Plasmodium falciparum infection, cerebral malaria, is primarily caused by the sequestration of infected erythrocytes in the microvasculature of the brain. Cytoadherence is known to be mediated through P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1), an infected erythrocyte surface protein that adheres to a variety of host cell receptors. On-going attempts at devising therapeutic or preventive interventions to prevent and/or alleviate rosetting are hindered by the fact that PfEMP1 is extremely polymorphic both between parasite strains and, due to the multi-copy nature of the genes encoding it, within single parasite strains. PfEMP1 is encoded by var genes and each var gene is mutually exclusively expressed and encodes a unique PfEMP1 protein. Previous studies have shown the expression of certain var genes is associated with cerebral malaria, and with the infected erythrocytes’ rosette-forming ability. The alignments of a functional erythrocyte binding domain of rosette-mediating PfEMP1 variants from assorted rosetting and non-rosetting PfEMP1 variants have revealed several predicted surface loops that may be involved in rosetting. Using CRISPR-Cas9 genome editing technology, this study will test the role of specific PfEMP1 regions and variants in rosette formation in P. falciparum. Ascertaining the role of PfEMP1 in rosette formation may aid in the development of new therapies for preventing and treating severe malaria.
Interests and expertise (Subject groups)