Project description
Novel anti-parasitic drugs
There is a great unmet medical need for therapeutics against parasite infections such as Chagas disease and leishmaniasis which are caused by Trypanosoma cruzi and Leishmania species, respectively. These eukaryotic parasites fall under the order of Kinetoplastida and possess a DNA-containing granule known as kinetoplast. Scientists of the EU-funded FEN INHIBITORS project will identify inhibitors of Kinetoplastida flap endonucleases, whose activity is crucial for the survival of all organisms tested so far. The project will undertake a multidisciplinary structure-based approach for the design of inhibitors and perform potency and toxicity studies of candidate molecules.
Objective
We are searching for Kinetoplastida flap endonuclease (FEN) inhibitors as a base for potential therapeutics for parasite infections, for which there is significant unmet clinical need. Kinetoplastida are flagellated protists responsible for 3 neglected human diseases. We will target the FEN enzymes from Trypanasoma cruzi and Leishmania species, the organisms causing Chagas disease and leishmaniaisis respectively. FEN activity is crucial for the survival of all organisms tested so far from mouse to bacteria, including Trypanosoma. We will identify specific inhibitors of Kinetoplastida FENs as the basis for future development of urgently needed new therapeutics. This multidisciplinary structure-based inhibitor design project will involve in vitro and in silico screening, protein crystallization, rounds of inhibitor design and finally in vivo potency and toxicity experiments.
The project will be overseen by Prof Sayers who has 30 years of experience with nucleases and who has founded two spin-out companies. His group is complemented through collaboration with a parasitologist Dr Helen Price (20 years research experience), who has been actively involved in developing antiparasitic agents. The experienced researcher, who has a strong protein biochemistry and crystallography background, is returning to academic research after almost 4 years outside science. Ultimately, the experienced researcher is aspiring to an academic career in translational medicine rooted in state-of-the-art basic research but with the skills and experience to synergise with the pharmaceutical sector.
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Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
S10 2TN Sheffield
United Kingdom