Project description
You may have it and not know it but help is on its way
Trichomoniasis is an extremely common sexually transmitted disease caused by the parasite Trichomonas vaginalis (T. vaginalis). The majority of people infected do not develop any symptoms, yet they can still spread the infection to others. Further, although two antibiotics exist to treat it, antibiotic resistance is a growing concern. Given the large number of people infected and unknowingly spreading the disease combined with emerging antibiotic resistance, Trichomoniasis is poised to be a serious public health challenge. ProTeCT is exploring a new route to effective therapy, focusing on a T. vaginalis proteosome. This multi-subunit complex plays an essential role in protein turnover and parasite survival. Elucidating the structure and function of subunits could provide important sites for targeted drug treatments.
Objective
Trichomoniasis, caused by the protozoan parasite Trichomonas spp., is the most common, non-viral, sexually transmitted infection in the world. Only two closely related antibiotic drugs are approved for its treatment. The accelerating emergence of resistance to current antibiotics and no alternative treatment options pose an increasing threat to public health, resulting in an urgent need for novel effective anti-parasitic compounds.
This project focuses on Trichomonas proteasome that is an underexploited enzyme critical for parasite survival. In this proposal, the proteasome will be functionally and structurally characterized. The substrate specificity of each subunit will be determined and fluorescent substrates that can monitor activity of each subunit will be designed. Libraries of proteasome inhibitors will be screened and hit compounds will be analyzed in co-crystallization studies with Tv proteasome. Ultimately, biochemical and structural data will be used to rationally design inhibitors for treatment of trichomoniasis.
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Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
16610 Praha 6
Czechia