powered by multiNETT - Internet-Systementwicklung
HEIDELBERG UNIVERSITY

Schirmer 
Protein networks that maintain redox homeostasis in malaria parasites and their hosts. Pathophysiology and drug therapy.

Groupleader: Heiner Schirmer
Informationen

Epidemiological and experimental evidence suggest that malaria parasites are more susceptible to reactive oxygen species than their human host cells. Antioxidative defense and redox homeostasis of the parasite are based on the glutathione and the thioredoxin systems. These systems form a network which involves dithiol proteins like glutathione reductase, glutaredoxins, thioredoxin reductase, and thioredoxin. The key enzymes of this antioxidative network are sufficiently different when comparing the malarial parasite Plasmodium falciparum, the insect vector Anopheles gambiae, and the human patient so that the design of specific inhibitors is warranted. These inhibitors might become of interest as antimalarial and/or as insecticidal agents (collaboration with PD H. M. Müller, EMBL).

Future projects will concentrate on glutathione-dependant processes in P. falciparum-parasitized erythrocytes (collaboration with Professor Katja Becker in Giessen). As members of the Research Focus SFB 544 Control of infectious diseases, we shall further work on the introduction of BlueCQ, an affordable combination of chloroquine and methylene blue, as an antimalarial drug. Methylene blue is a specific inhibitor of P. falciparum glutathione reductase but has a number of desired and unwanted side effects which are related to its redox properties. This project – a collaborative effort with the Centre de Recherche en Santé de Nouna (CRNS in Burkina Faso) and Drs. Schiek and Zich (DSM, Linz) is supported by the DSM Dream Action Award 2002.

Thioredoxin system and selenium metabolism. Another research focus of our group are Dr. Gromer´s studies on the interactions between thioredoxin system and selenium metabolism in infectious diseases and malignancies.