Yvonne Adams

Associate prof and Group Leader, Dept. of Immunology and Microbiology

Title: The blood-brain barrier and beyond: Investigating the impact of cerebral malaria on blood-brain barrier dysfunction

Abstract: Malaria, a parasitic disease transmitted by the bite of infected mosquitoes remains one of the leading causes of morbidity and mortality of children under the age of 5 in sub-Saharan Africa. The disease presents with flu-like symptoms and periodic fevers linked to parasite expansion within the patient. The Plasmodium falciparum parasite invades human red blood cells (iRBC) and avoids splenic destruction by binding to the lining of blood vessels. It can present as uncomplicated, severe, or cerebral malaria (CM). CM is characterised by the sequestration of these iRBC to the lining of the capillaries within the human brain, triggering inflammation, resulting in changes in surface receptor expression such as an increase in ICAM-1. This increase lead to the recruitment of more iRBCs, culminating in vessel occlusion. In approximately 15-20% of cases, the disease is fatal. Death occurs due to compression of the brain stem via sudden, excessive swelling of the brain. In those surviving CM, many are left with life-long neurological sequalae.

The exact mechanisms which trigger this swelling are not fully understood, nor is the impact of the adhesion of specific subsets of parasites on the blood-brain-barrier (BBB). Our research is focused on understanding how parasites which can utilise ICAM-1 and EPCR simultaneously trigger BBB dysfunction. To answer these questions, we use BBB-organoids as a human derived model of malaria infection. Our BBB-organoid model recapitulates the interactions between the components of the BBB (endothelial cells, pericytes and astrocytes). These cells self-assemble into organoids (250-350 µm in diameter), forming an “inside-out” model of the BBB, that mimics the in vivo environment. By using this model, we can measure the ability of infected red blood cells to bind to and disrupt the normal functions of the BBB. A greater understanding of how the malaria parasites disrupt not only the tight junctions of the BBB, but active transport across the BBB, will allow for the identification and development of drug interventions to limit or abrogate the damage caused during CM and improve the quality of life for survivors. 

Location: Holst Auditorium