Analysis of the haemoglobin catabolism of Plasmodium falciparum proliferation in genetically modified erythrocytes

• Grant number: 12/12790-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: February 01, 2013
• End date: February 28, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Carsten Wrenger
• Grantee: Jasmin Lindner
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 09/54325-2 - Elucidation of vitamin B metabolism in the human malaria parasite Plasmodium falciparum and their validation as a target for chemotherapy, AP.JP

Abstract

Highly proliferating cells such as the malaria parasite Plasmodium falciparum necessitate an accelerated level of carbohydrates for energy supply for maintenance of intracellular processes. Besides sugars one of these sources are amino acids which are imported from the host cell plasma and by digestion of haemoglobin within the food vacuole. During haemoglobin digestion heme is going to be released which needs to be detoxified into hemozoin. Humans who harbours erythrocytic diseases related to the haemoglobin architecture such as sickle cell disease or alpha- or beta thalassaemia gain a protective advantage while infected with the malaria pathogen. Within this project it is intended to get insights into the mode of action of parasite growth within genetically different erythrocytes will be analysed by focussing on the plasmodial haemoglobin catabolic pathway using transgenic parasites. Furthermore, the respective localization of catabolic enzymes will be investigated by fluorescence microscopy using green-fluorescent-protein- chimeras and selective plasmodial haemoglobin catabolic enzymes will be recombinantly expressed in order to obtain structural details. The parasite´s nutrient metabolism shelters a high potential for the development of novel drug targets. Therefore a clear understanding of the occurring haemoglobin digestion and the protective nature of haemoglobin variants is essential. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

KRONENBERGER, THALES; LINDNER, JASMIN; MEISSNER, KAMILA A.; ZIMBRES, FLAVIA M.; CORONADO, MONIKA A.; SAUER, FRANK M.; SCHETTERT, ISOLMAR; WRENGER, CARSTEN. Vitamin B6-Dependent Enzymes in the Human Malaria Parasite Plasmodium falciparum: A Druggable Target?. BIOMED RESEARCH INTERNATIONAL, 2014. (11/19703-6, 12/12807-3, 11/13706-3, 09/54325-2, 10/20647-0, 13/10288-1, 12/12790-3)

MURAD, ALINE MELRO; BROGNARO, HEVILA; FALKE, SVEN; LINDNER, JASMIN; PERBANDT, MARKUS; MUDOGO, CELESTIN; SCHUBERT, ROBIN; WRENGER, CARSTEN; BETZEL, CHRISTIAN. Structure and activity of the DHNA Coenzyme-A Thioesterase from Staphylococcus aureus providing insights for innovative drug development. SCIENTIFIC REPORTS, v. 12, n. 1, p. 14-pg., 2022-03-12. (17/03966-4, 12/12790-3, 15/26722-8)

KRONENBERGER, THALES; LINDNER, JASMIN; MEISSNER, KAMILA A.; ZIMBRES, FLAVIA M.; CORONADO, MONIKA A.; SAUER, FRANK M.; SCHETTERT, ISOLMAR; WRENGER, CARSTEN. Vitamin B6-Dependent Enzymes in the Human Malaria Parasite Plasmodium falciparum: A Druggable Target?. BIOMED RESEARCH INTERNATIONAL, v. 2014, p. 11-pg., 2014-01-01. (13/10288-1, 10/20647-0, 12/12790-3, 09/54325-2, 11/13706-3, 12/12807-3, 11/19703-6)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

LINDNER, Jasmin. Analysis of the haemoglobin catabolism of Plasmodium falciparum.. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.