Signaling pathways and function of Plasmodium falciparum serpentine receptors SR1 and SR10

Abstract

Parasites of the genus Plasmodium are the causative agents of malaria, a disease that affects millions of people around the world annually. The emergence of parasites resistant to classic antimalarials used in the treatment of the disease points to the importance of understanding the biology of the parasite and looking for new targets for the development of new antimalarials. The synchronous and coordinated development of the malaria parasite presents a way for the parasite to evade the host's immune system and ensure the progression of the infection, thus elucidating the signaling pathways and the cellular machinery involved in the synchronization of the parasites is of great significance to search for new targets. Previous studies have shown that melatonin, a hormone produced bythe host's pineal gland, plays an important role in parasite synchronization and triggers a signaling pathway involving different kinases, including PfeIK1, involved in protein translation. However, the melatonin receptor in Plasmodium has not yet been identified. In previous studies, four serpentine receptors were identified in the genome of the P. falciparum parasite, namely SR1, SR10, SR12 and SR25. In this postdoctoral project we propose to use nanoluciferase complementation techniques in a heterologous expression system and techniques such as nanoBRET to investigate the role of Plasmodium receptors SR10 and SR1. In addition, we will investigate the phenotypic characteristics of these receptors using transgenic parasites. (AU)