A vacuolar lipocalin as a candidate regulator of hemoglobin catabolism and hemozoin formation in the malaria parasite

• Applicant: Dr. Joachim Michael Matz
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens ; Cell Biology
• Term: from 2019 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 419345764

Malaria is a significant burden on the public health and fragile economies of developing countries. The distinct pathology of malaria is caused by the propagation of Plasmodium parasites in the human bloodstream. Here, this unicellular pathogen invades erythrocytes and digests vast amounts of hemoglobin inside a specialized organelle, called the digestive vacuole. During hemoglobin degradation, large quantities of the prosthetic group heme are released, which causes a variety of cytotoxic effects in its unbound form. Thus, the parasite sequesters heme into an inert crystal, the so-called malaria pigment or hemozoin. The factors regulating hemoglobin digestion and heme biomineralization are only poorly understood. I have identified a candidate regulator of these processes, called PV5. Sequence analysis suggests, that PV5 is a lipocalin. Proteins of this family bind diverse ligands in their barrel-like binding pockets and function in a variety of molecular processes. PV5 localizes to the digestive vacuole, where it participates in a soluble protein complex. I bring forward the hypothesis that PV5 is a heme-dependent regulator of the hemoglobin digestion machinery, controlling the rate of hemoglobin catabolism and intracellular heme concentrations. I propose a complementary strategy that approaches PV5 function in the human malaria parasite P. falciparum by reverse genetics and protein interaction studies. The proposed investigations aim to identify the interaction partners of PV5 and analyze the consequences of PV5 ablation.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Dr. Mike Blackman