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

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)