Identification of melatonin-regulated proteins that are involved in the cell cycle of Plasmodium falciparum

Malaria remains one of the leading infectious diseases in the developing world. During the last decade, the world has made great progress in the fight against malaria (WHO 2013), but the emergence of resistance to antimalarials and insecticides has become a major problem to be considered. Therefore, new chemotherapy approaches with alternative targets are needed (Doerig, Baker et al., 2009). Although some progress has been made, many of the signaling pathways that control the development of the asexual intraerythrocytic forms of the pathogen (ring to trophozoite and schizont stages of Plasmodium falciparum) remain essentially uncharacterized. It was shown that the asexual phase of P. falciparum responds to melatonin (and its derivatives, tryptamine, serotonin N-acetyl serotonin and N1-acetyl-N2-formyl-5-methoxykinuramine) by modulating the proliferation cycle in vitro (Hotta , Gazarini et al., 2000, Budu, Peres et al., 2007). Furthermore, Plasmodium parasites are capable of sensing host signaling and modulating its function through a complex cellular machinery of membrane receptors (Garcia, Mark et al., 2001, da Madeira, Ga et al. 2008 Koyama, Chakrabarti et al., 2009 Budu and Garcia, 2012). To achieve our goal, the intention is to generate parasites with endogenous genes marked with GFP, which will allow us to follow the activation stimulus in living cells, as well as generate parasites with adjustable levels of these proteins of interest to allow us to study how their removal alters/removes the response to stimuli. These experiments will provide information about the signaling and direct mechanisms of expression of these proteins, as well as mediating the correct subcellular localization within the parasite cell and the infected host.

Project Details

Basic Science

Apr 2015 — Mar 2016

Brazil