Identification of proteins regulated by melatonin signal transduction that are involved in the celular cycle of Plasmodium falciparum

• Grant number: 14/26067-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: April 01, 2015
• End date: March 31, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal Investigator: Célia Regina da Silva Garcia
• Grantee: Giulliana Tessarin e Almeida
• Supervisor: Jude Przyborski
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Philipps-Universität Marburg, Germany
• Associated to the scholarship: 13/13361-1 - Deep Sequencing (RNA-seq) to detect differentially expressed genes involved in the modulation of cell cycle of Plasmodium falciparum, BP.PD

Abstract

Malaria remains a major infectious disease in the developing world. Over the last decade, the world has made much progress in the fight against malaria(WHO 2013), however, the emergence of resistance to conventional antimalarial drugs and insecticides is still a major problem which needs to be addressed. Thus, new chemotherapeutic 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 pathogenic asexual intraerythrocytic forms through ring, trophozoite and schizont stages of Plasmodium falciparum remain essentially uncharacterized. Our group has shown that asexual blood stage P. falciparum parasites respond to melatonin (and its derivatives, tryptamine, serotonin N-acetyl serotonin and N1-acetyl- N2-formyl-5-metoxykynuramine) by modulating their proliferation cycle in vitro (Hotta, Gazarini et al. 2000, Budu, Peres et al. 2007). Moreover Plasmodium parasites are able to sense host signals to modulate its function through a complex cellular machinery and membrane receptors (Garcia, Markus et al. 2001, Madeira, Galante et al.2008, Koyama, Chakrabarti et al. 2009, Budu and Garcia 2012). The present proposal intends to identify the role of two of proteins regulated by melatonin signal transduction, which could be involved in the activation of genes from the ubiquitin proteosome system (UPS). To achieve our goal we aim to generate parasites with endogenous genes tagged with GFP to allow us to follow activation upon stimulus in a live-cell setting and furthermore generate parasites with adjustable levels of the proteins of interest to allow us to study how removal of these proteins alters/ablates response to stimuli. These experiments will give information on both the signals and mechanisms directing expression of these proteins, and also mediating their correct subcellular localization within the parasite and infected host cell. (AU)