Malaria immunity targets team (TARGETS)
Research in the TARGETS team is focused on a family of "sticky" proteins known as the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). P. falciparum is the most pathogenic malaria parasite and a major cause of morbidity and mortality among children in sub-Saharan Africa.
Our current research projects include in vitro molecular and immunological characterization of PfEMP1 proteins associated with cerebral malaria in young children.
The pathogenesis of P. falciparum malaria is closely associated with the ability of PfEMP1 to adhere to host endothelial cells (Immunol Rev).
We have identified PfEMP1 molecules linked to severe malaria in children infected by P. falciparum (J Exp Med; J Immunol; Infect Immun). A particular subset of such PfEMP1 molecules bind both ICAM-1 and EPCR, and is associated with increased risk of developing cerebral malaria (Cell Host Microbe).
Using a 3D spheroid model of the blood-brain barrier (Top figure, right and video), we recently showed (J Exp Med) that dual-receptor binding IEs (in red) are taken up by brain endothelial cells (Figure). Ex vivo analysis confirmed the presence of parasites within brain endothelial cells of postmortem tissue samples from CM patients (Figure insert).
This unexpected discovery points to parasite ingress into the brain endothelium as a contributing factor to the pathology of human CM. Read more about this discovery at the Advanced Science web site.
Current research projects include in vitro molecular and immunological characterization of PfEMP1 proteins associated with cerebral malaria in young children and brain endothelial cell responses to these proteins.
The members of the TARGETS team cover a wide range of skills within malariology, immunology, molecular, structural and cell biology. The team is involved in a number of national and international research collaborations, e.g. MAVARECA-II.
Techniques used include 3D cell culture (BBB spheroids), genetic engineering, DNA sequencing, protein expression and purification, biosensor assays, Luminex assays, flow cytometry, hybridoma techniques, real-time quantitative PCR, flow based cellular adhesion assays, manipulation and culturing of P. falciparum malaria parasites.
We welcome graduate and undergraduate students with a background in Health & Medical Sciences and Natural Sciences to do their project with the TARGETS team. If you are interested, please contact the team leader, Professor Anja Jensen.
Our research is supported by several major grants with Lundbeckfonden being the current main sponsor.