Project description DEENESFRITPL Drug repurposing for the disruption of bacterial biofilms Bacterial biofilms (BB) are clusters of bacteria embedded in their own matrix, associated with chronic infections with higher tolerance to antibiotics. Secondary messenger cyclic di-GMP (cdGMP) promotes biofilm formation and is a potential target in the BB disruption strategies. The EU-funded DRIPBEAT project aims to repurpose drugs for targeting the cdGMP pathway and biofilms, increasing the antibiotic susceptibility of clinically important Pseudomonas aeruginosa strains. The interdisciplinary study will combine next-generation sequencing technology and protein structural modelling in a murine model of lung epithelial cell infection. The results will provide new insights into the cdGMP pathway and the selection of appropriate compounds for BB treatment. Show the project objective Hide the project objective Objective Bacterial biofilms are closely associated with chronic infections, leading to much higher tolerance to antibiotics and treatment failures. New strategies for biofilm disruption are thus urgently required. Cyclic-di-GMP, a secondary messenger promoting biofilm formation, is a promising drug target. Only few compounds that reduce c-di-GMP levels and inhibit biofilms were identified so far, and most studies were conducted in vitro using standard medium and reference strains. In this project drugs will be repurposed for targeting c-di-GMP and biofilms to increase the antibiotic susceptibility of clinical Pseudomonas aeruginosa strains. Interdisciplinary approaches will be applied, combining next generation sequencing, gene expression pattern in synthetic sputum, protein structural modelling and computational drug docking, lung epithelial cell infection and murine model. This project will increase the accuracy of drug discovery based on c-di-GMP and significantly expand the skillset of an early career researcher with a strong background in the molecular mechanism of c-di-GMP pathway. The new knowledge in human cell culture and murine model obtained in this fellowship will be crucial for the researcher with a long-term interest in infection treatment. The host laboratory at Ghent University (UGent), a leading group in Europe investigating combination therapy against biofilms, offers an excellent atmosphere fostering both technical and transferable skills. The researcher will also benefit from the supervisor’s extensive research network and the numerous training programs provided by UGent to enhance the future career prospects. The research outputs will provide fresh insights into how genetic and environmental conditions influence c-di-GMP pathway (basic science) and how to select more appropriate compounds for biofilm treatment (applied science), and may also be subjected to clinical trials and attract industrial partners for wider applications. Fields of science natural sciencesbiological sciencesmicrobiologybacteriology Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2020 - Individual Fellowships Call for proposal H2020-MSCA-IF-2020 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator UNIVERSITEIT GENT Net EU contribution € 166 320,00 Address SINT PIETERSNIEUWSTRAAT 25 9000 Gent Belgium See on map Region Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 166 320,00
