Dissect the molecular mechanism for Plasmodium falciparum serpentine receptor 12 activation in mammalian systems

Unlike what has been described in the literature by bioinformatics experiments that showed PfSR12 as a purinergic receptor, Ca2+ release was not observed in HEK297T system after purine treatments, but a statistically significant response was indeed observed in Ca2+ release after thrombin addition to cell culture. The indications that PfSR12 would be a thrombin receptor are of great importance, since parasite proteins capable of interacting with molecules of the host’s coagulation system are still unknown and the presence of receptors activated by proteases is extremely rare. After identifying thrombin as a PfSR12 ligand, the action of this protein was verified in an in vitro culture of P. falciparum. Supplementation of the culture medium with thrombin did not change the duration of the parasite cycle, the total time of each stage of the cycle, or the morphology of the parasite. However, an increase in parasitemia was observed in cultures incubated with thrombin when compared to unsupplemented cultures. There is a reason to believe that thrombin interacts directly with the parasite, influencing the exit/invasion process of new cells. The action of thrombin may be mediated by PfSR12, which induces a signaling cascade that culminates in greater efficiency in the invasion/exit process, or even in the formation of new cells. The experiments described in this project will allow us to define molecular aspects of the thrombin and SR12 signaling pathway.

Project Details

Basic Science

Sep 2018 — Jul 2019

Brazil