Role of L-glutamine in the protection of Trypanosoma cruzi and Trypanosoma brucei against programmed cell death

• Grant number: 15/09039-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: November 01, 2015
• End date: October 31, 2016
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Ariel Mariano Silber
• Grantee: Flávia Silva Damasceno
• Supervisor: Michael Duszenko
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Eberhard Karls Universität Tübingen, Germany
• Associated to the scholarship: 13/09851-3 - Role of glutamine synthetase in the biology of Trypanosoma cruzi, and perspectives as a possible therapeutic target, BP.DR

Abstract

Trypanosoma cruzi and Trypanosoma brucei are the etiological agents of Chagas' disease and sleep sickness, respectively. Both are able to catabolize amino acids, which are involved in important metabolic processes. During the life cycle, the parasites adapt their metabolism to the availability of substrates in the different environments they go through along their life cycles. It was already described that the amino acids are involved in different biological processes, such as, osmoregulation, resistance to metabolic, thermal and oxidative stress; differentiation and proliferation. In my PhD project we showed that glutamine participates in important biological processes such as differentiation, infectivity, intracellular cycle, proliferation and energetic metabolism. We are interested in evaluate if glutamine has the same roles in T. brucei, and its possible participation in preventing programmed cell death in both organisms. During the life cycle of parasites occurs nutritional stress, and starvation is a potent inducer of autophagy and organelle recycling in diversity of cells. Autophagy was shown to be important for T. cruzi survival during starvation and differentiation. Only if starvation continues or if strong cell death signals are triggered with a simultaneous block of apoptosis, autophagy continues and finally results in an organized cell death. In this project the main goal is to unveil the participation of glutamine as well as the enzyme that catalyzes its biosynthesis from glutamate, glutamine synthetase, in the programmed cell death mechanisms associated to metabolic stress in both, Trypanosoma cruzi and Trypanosoma brucei. More speciffically, we aim to investigate the importance of the glutamine in Trypanosoma brucei by using RNAi against glutamine synthettase. We expect that these results will contribute to understand the role of glutamine in the biology of trypanosomes. Moreover, we expect that our results will shed a light on new druggable targets for the fight against sleeping sickness, and Chagas' disease. (AU)