Principal Investigator: Nahla Galal Metwally 🇪🇬
Funding (Leibniz center of infection , Jürgen Manschot Stiftung)
PhD scholarship applications are welcomed (DAAD, Jürgen Manschot, etc..), for this please, drop me an email (email@example.com).
Establishing the causal role of any single mechanism in severe malaria in humans is difficult. The pathogenesis of severe malaria is hotly debated; some suggest that cytoadhesion is the overriding pathogenic mechanism, whilst others believe that inflammatory processes are more important. An accumulating body of evidence indicates that vascular endothelial dysfunction is also important and could be the interface between cytoadhesion and inflammation.
Several cellular signaling pathways, including immune signaling pathways, need to be fine-tuned during infection, and some of these are regulated by miRNAs. miRNAs are non-coding RNAs of ~20 nucleotides in length that occur in mammals, plants and viruses. The human genome is estimated to contain 2300 true human mature miRNAs, of which 1115 are currently annotated, according to miRBase version 22
Our proposed theory
Our hypothesis is that the dysfunction of ECs is a trigger for severe malaria complications. This disrupts the balance between vasoconstriction and vasodilatation and predisposes to cytoadhesion of iRBCs, endothelial proliferation and leakage of the BBB. By regulating gene expression within ECs, certain miRNA candidates may be involved in controlling these events. These miRNAs may sense the presence of IEs through cell-cell communication between iRBCs and ECs.
In this project, we scan the human miRNA profiles in the different cells that are involved during the major events of severe P. falciparum infection and cerebral malaria. The experiments are designed to monitor the first steps and role of parasite or host factors in triggering complications.