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National Repository of Grey Literature 2 records found  Search took 0.00 seconds. 
Selected proteolytic aspects as targets to combat ticks and tick borne pathogens
 HARTMANN, David
Ticks and tick-borne diseases (TBD) represent a growing global burden for both human and animal health. Tick-host-pathogen interactions have evolved through dynamic processes that accommodated the genetic traits of the hosts, pathogens transmitted, and the vector tick species that mediate their development and survival. As in other parasites, proteases and proteolysis have been found as one of the key factors in this interaction triangle. This thesis is focused on selected proteolytic aspects of tick and tick-borne diseases: (i) processing of host blood as a source of nutrients and energy (hematophagy) as a continuum of the long-term goal of the Laboratory of Vector Immunology, that established the currently accepted model of multienzyme degradation of host blood proteins by ticks (ii) proteases in innate immunity (iii) validation of Babesia proteasome as a potential therapeutic target against the tick transmitted apicomplexan parasites.
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Kultivace klíšťaty přenášených babesií a charakterizace jejich proteasomu jako nového terapeutického cíle
 REICHENSDÖRFEROVÁ, Dominika
Tick-transmitted parasites of the genus Babesia represent an important worldwide veterinary threat and an emerging risk to humans. In comparison to their malaria-causative relatives, these erythrocyte infecting Apicomplexa have been widely neglected and no specific treatment has been developed. Thus, this thesis is focused on the optimised cultivation of the two species: B. divergens in bovine erythrocyte cultures (in vitro) and B. microti in BALB/c mice (in vivo). Since the Babesia 26S proteasome has been recently validated by our laboratory for drug development we applied different strategies used to isolate the P. falciparum 26S proteasome to optimize its isolation from the two babesia species - ultrasonication, mechanical homogenization and ultracentrifugation. In addition, we used ion exchange chromatography to purify the 26S proteasome from B. microti lysates. Future steps will involve optimised protocols using either ion exchange, immunoprecipitation and/or ubiquitin affinity to purify volumes of B. microti proteasome suitable for substrate specifity profiling of the proteolytic subunits as well as for 3D protein studies involving Cryo-EM or conventional protein crystalography. The overal goal of the long term laboratory project is to produce and validate novel Babesia selective proteasome inhibitors that could be developed into yet missing specific treatment for babesiosis.
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