|X-Ray Crystallography Laboratory|
The project entitled:
"Characterization of Trypanosoma cruzi PEX5 as a promising target in Chagas disease."
funded by National Centre of Science, Poland between 2018 and 2021.
Parasitic diseases are amongst the foremost threats to human health and welfare around the world. Chagas disease, the infection caused by Trypanosoma cruzi, is devastating both in terms of human morbidity and mortality in central Americas and spreads continuously to new regions owned to human population movements. The currently available drugs are limited, often ineffective, and require long treatment regimens resulting in significant side effects. Moreover, resistance is becoming a burning problem. To overcome these limitations, the identification of new macromolecular drug targets and small-molecule modulators is of utmost importance, which is addressed in this project.
Unlike mammalian cells, glycolysis in Trypanosoma is compartmentalized in unique organelles (glycosomes) which are essential for parasite survival. Glycosomes lack protein production abilities and import needed enzymes using peroxin (PEX) system. Cytosolic receptor (PEX5) recognizes peroxisomal targeting signal 1 (PTS1) harboring proteins. Cargo loaded PEX5 docks at PEX14 at the glycosomal membrane. With the help of other PEX proteins the cargo is delivered into the glycosome. It has been demonstrated by our Partner in the project that pharmacological disruption of PEX14/PEX5 interaction is lethal for the parasites, making it a potential drug target against trypanosomiasis. However, the most suitable point of intervention in the PEX pathway remains to be determined. The primary aim of this project is to validate protein-protein interactions (PPI) within the PEX pathway as suitable targets for generation of new antiparasitic drugs in Chagas disease.
If you are interested in obtaining further detailed information on the project please contact me by mail.