Neutrophil elastase significantly contributes to cystic fibrosis (CF) lung disease by causing lung damage and inflammation. The majority of adult patients with CF have Pseudomonas aeruginosa chronic lung infections and P. aeruginosa elastase further aggravates tissue destruction. The goal of this project is to generate nanomedicines able to inhibit the proteolytic activities of murine neutrophil elastase and P. aeruginosa elastase and to assess these inhibitors as a local treatment in murine lung infection models of P. aeruginosa. The project will include the production of long-acting anti-elastase nanomedicines, their physicochemical and biological characterization in vitro and their assessment in vivo for pharmacokinetics and therapeutic efficacy.
This competitive 48-month project is funded by the Fonds National de la Recherche Scientifique (www.fnrs.be ). The project will be co-supervised by Prof. Rita Vanbever (Louvain Drug Research Institute, UCLouvain) and Dr. Mireille Dumoulin (Center of Protein Engineering, University of Liège) and will be performed in collaboration with Prof. Frédéric Tewes of the University of Poitiers (Pharmacology of antimicrobial agents and resistances) in whose laboratory, the PhD student will perform in vivo efficacy studies over the last 6 months of the PhD. You will receive a 12-month doctoral fellowship with a net allocation of 2100€ per month. The fellowship can start between June and September 2022 and will be renewable thrice for a total of 48 months.
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