Metabolic investigation in trypanosomatids using steady-state free precession (SSFP) nuclear magnetic resonance

• Grant number: 12/04281-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2012
• End date: January 31, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Otavio Henrique Thiemann
• Grantee: Matheus Pereira Postigo
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 08/57910-0 - National Institute of Structural Biotechnology and Medicinal Chemistry in Infectious Diseases, AP.TEM
• Associated scholarship(s): 14/19182-4 - Metabolic profile identification of Trypanosoma Cruzi in cooperation with Leiden University, the Netherlands, BE.EP.PD

Abstract

Tripanossomiasis and leishmaniasis are widely distributed in Brazil, and the control of these diseases consists mainly of chemotherapy treatments. Despite the proven efficacy of some compounds currently in use, some failure cases are often reported. Furthermore, the drugs currently available are administered for a long period and show severe toxicity. Two important aspects are being investigated: 1) the effect of gene depletions on the metabolism of the parasite target, identifying new molecular targets for drug development and 2) tests for screening biochemical targets for new drugs or compounds on the parasites. The key point of this study is the use of NMR techniques metabolomics/metabonomics investigation of Kinetoplastidae subject to gene depletion by RNA interference and identification of molecular targets and pathways affected by several drugs (e.g. Benznidazole) and drug candidates (e.g. Auranofin). These studies will allow the use of this technique in different laboratories by different experimental approaches, resulting in a significant contribution to the investigation of these organisms. (AU)