Characterization of the protein interactors of Plasmodium falciparum Hsp70 (PfHsp70-1): towards the development of small-molecule inhibitors of PfHsp70-1 chaperone function

• Applicant: Professor Dr. Klaus Lingelbach (†)
• Co-Applicants: Professor Dr. Gregory Lloyd Blatch; Professor Addmore Shonhai, Ph.D.
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2009 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 68955586

Plasmodium falciparum is the causative agent of malaria tropica which is responsible for most of the deaths caused by malaria. The pathology of the disease is the result of parasite growth and replication within human erythrocytes. Within its host, the parasite is very well adapted to stress conditions such as high febrile temperatures; in fact several studies suggest that acute temperature increases augment parasite development and infectivity. The subject of this project is the P. falciparum heat shock protein 70-1 (PfHsp70-1) which is expressed throughout all intra-erythrocytic stages. Hsp70 proteins form a ubiquitous and conserved family of molecular chaperones whose main function is to ensure the correct folding of other protein substrates, usually in cooperation with other heat shock proteins. Although PfHsp70-1 has properties that are similar to mammalian Hsp70 (chaperone functions, increased levels under stress conditions), work in the South African laboratory have also revealed biochemically distinct properties. According to our working hypothesis, these distinct properties represent evolutionary adaptations to an intracellular and parasitic life. Therefore we aim to identify the functional partner proteins and substrate proteins of PfHsp70-1 to precisely define the parasite-specific functions of this protein. The ultimate aim is to use this information for the development of specific inhibitors as lead compounds for novel anti-malarial drugs.

• DFG Programme: Research Grants
• International Connection: South Africa
• Participating Persons: Professor Dr. Jude Marek Przyborski; Professor Dr. Richard Zimmermann