Transcriptomic profiling in an in vitro model and post-mortem tissue samples to investigate sequestration driven pathology in cerebral malaria

Cytoadherence of Plasmodium falciparum parasitised red blood cells (pRBC) to endothelium is a hallmark of human cerebral malaria (CM) but is absent in rodents. We have developed an in vitro model whereby pRBC are cultured with primary brain endothelial cells – pRBC cytoadhere – leading to endothelial and coagulation activation. A variety of manipulations are possible. We aim to validate the biological relevance of this in vitro model by comparing findings from archival post-mortem tissue from people with CM. Transcriptomics provides a means to profile and compare key cellular activities in the endothelium from post-mortem brain tissue and the in vitro model, providing an indication of the similarities and differences between these distinct but potentially complementary sources. We want to identify differentially regulated pathways induced specifically by pRBC in both post-mortem and in vitro samples.

If feasible this would enable mechanistic examination and screening of candidate drugs in vitro to targets identified to be relevant to disease in patients.