Descrizione del progetto
Nuovi farmaci antiparassitari
Un’importante esigenza medica non soddisfatta riguarda le terapie contro le infezioni parassitarie come la malattia di Chagas e le leishmaniosi, causate rispettivamente da specie di Trypanosoma cruzi e Leishmania. Questi parassiti eucarioti rientrano nell’ordine dei cinetoplastidi e possiedono un granulo contenente DNA noto come cinetoplasto. Gli scienziati del progetto FEN INHIBITORS, finanziato dall’UE, identificheranno gli inibitori dell’endonucleasi flap dei cinetoplastidi, la cui attività è fondamentale per la sopravvivenza di tutti gli organismi testati fino ad ora. Il progetto seguirà un approccio multidisciplinare basato sulla struttura per la progettazione di inibitori ed effettuerà studi di potenza e tossicità delle molecole candidate.
Obiettivo
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.
Campo scientifico
Parole chiave
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Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
S10 2TN Sheffield
Regno Unito