Project description DEENESFRITPL Novel light-activated antimicrobials Antimicrobial resistance is emerging as a significant medical issue, with many pathogens that used to be amenable to antibiotic treatment suddenly becoming resistant. This clearly indicates the need for new drugs. To combat antimicrobial resistance, the EU-funded PhotoLiB project proposes to develop lipid-based drugs that can be activated using light. Exploitation of light to modulate the chemical properties of drugs is known as photopharmacology, and it is an attractive approach considering that light is non-toxic and can be delivered with high precision at specific sites. The PhotoLiB drugs will have the capacity to penetrate and disrupt bacterial membranes, offering safe alternatives to existing antimicrobials. Show the project objective Hide the project objective Objective Antimicrobials have saved millions of lives since they were first discovered. Unfortunately, today the world is facing up a global antibiotic resistance health emergency. In fact, bacterial infections which have been susceptible to standard antibiotic regimes for decades are now becoming resistant to all major antimicrobial treatments, making their efficacy undermined. Within this context, this proposal aims to develop a new and original strategy to combat antimicrobial resistance. Photopharmacology is a novel and emerging medical approach which exploits light to modulate the activity of drugs. The energy of light, which is not toxic to humans and easily delivered with high precision, can be used to change, at will, the conformation and chemical properties of drugs, making them more selective and efficient. This project wants to apply the photopharmacology concept to amphiphilic lipid drugs, namely those molecules bearing a polar head and a lipid tail acting as antimicrobials through disruption of bacterial membranes. Since, unlike other proteins and enzymes, membranes cannot mutate, they are ideal targets to combat antimicrobial resistance. New Photoswitchable Amphiphilic Lipis (PALs), able to intercalate the bacterial membranes, will be developed and synthesised by inserting a photoactivable probe into a amphiphilic lipid. Upon light irradiation, these PALs will change conformation leading, selectively, to membrane damage and consequent cell death. A set of 20 PALs will be synthesised and the compounds will be evaluated against a panel of bacteria, alone or in synergistic combination with other antibiotics. Preliminary in-vivo studies on Galleria models will be carried out as well as NMR-metabolomic studies to elucidate the key interactions of PALs with living systems and the response of bacteria to the action of these new drugs. The data generated through this project will create new means and opportunities in the fight against bacterial resistance. Fields of science natural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsmedical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistancenatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Keywords Photopharmacology antimicrobial resistance antibacterials drug discovery NMRmetabolomic 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 - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator UNIVERSITY COLLEGE LONDON Net EU contribution € 151 686,91 Address GOWER STREET WC1E 6BT London United Kingdom See on map Region London Inner London — West Camden and City of London 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 € 151 686,91 Participants (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all KING'S COLLEGE LONDON Participation ended United Kingdom Net EU contribution € 61 246,85 Address STRAND WC2R 2LS London See on map Region London Inner London — West Westminster 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 € 61 246,85
