Project description DEENESFRITPL Investigating the antibiotic potential of lipid droplets Lipid droplets (LDs) are not simply a source of nutrients for invading microorganisms. Recent research has shown that they can also possess antibiotic activity. The EU-funded DRIMMS project will investigate the role of LDs in the innate immune response of eukaryotic cells. Using high-throughput proteomics and lipidomics, 3D electron tomography, confocal microscopy and biochemical methods, the project will characterise how LDs coordinate and execute immune responses. It will also study the response to Mycobacterium tuberculosis to understand how it resists LD-mediated defences. The project’s findings will be useful for the development of new anti-infective therapies, especially in the face of growing antimicrobial resistance and viral pandemics. Show the project objective Hide the project objective Objective Successful defence against invaders is critical for survival of eukaryotic cells. Microbes have developed many strategies to subvert host organisms which, in turn, evolved several innate immune responses to counterattack. As major lipid storage organelles of eukaryotes, lipid droplets (LDs) are an attractive source of nutrients for invaders. Pathogens induce and physically interact with LDs and the current view is that they ‘hijack’ LDs to draw on substrates for host colonisation. We recently challenged this dogma by demonstrating that LDs are endowed with a regulated protein-mediated antibiotic activity. Our work intro-duced the new concept that dependence on host nutrients is a generic ‘Achilles’ heel’ of intracellular pathogens and LDs a chokepoint harnessed by innate immunity to organise a front-line defence.Here, we have formed a multidisciplinary group combining complementary knowledge and transdiscipli-nary expertise to investigate the hypothesis that LDs are innate immunity hubs sensing infection and di-rectly confronting invaders. We will characterise, in cells and animals, how LDs efficiently coordinate and precisely execute a plethora of immune responses such as killing, signalling and inflammation. High-throughput proteomics and lipidomics will identify defensive players. 3D electron tomography and confo-cal microscopy will be combined with proximity labelling strategies and biochemical methods to get un-precedented understanding of host LD-pathogen dynamics. The successful pathogen Mycobacterium tuber-culosis will be used to test the medical significance of our findings and unravel bacterial mechanisms of resistance to LD-mediated defences.Characterisation of these novel innate immune systems will be paradigm-shifting in immunology, physiol-ogy and cell biology. In the age of antimicrobial resistance and viral pandemics, unravelling how eukaryot-ic LDs fight and defeat dangerous microorganisms will inspire new anti-infective therapies. Fields of science medical and health scienceshealth sciencespublic healthepidemiologypandemicsmedical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesclinical medicinepneumologytuberculosismedical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance Keywords Lipid droplets bacteria tuberculosis lipids mitochondria cell biology electron microscopy proteomics Programme(s) HORIZON.1.1 - European Research Council (ERC) Main Programme Topic(s) ERC-2022-SyG - ERC Synergy Grants Call for proposal ERC-2022-SYG See other projects for this call Funding Scheme ERC-SYG - ERC-SYG Coordinator FUNDACIO DE RECERCA CLINIC BARCELONA-INSTITUT D INVESTIGACIONS BIOMEDIQUES AUGUST PI I SUNYER Net EU contribution € 3 141 849,00 Address Carrer rossello 149 08036 Barcelona Spain See on map Region Este Cataluña Barcelona Activity type Research Organisations 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 Other funding € 0,00 Participants (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all THE UNIVERSITY OF QUEENSLAND Australia Net EU contribution € 3 367 309,00 Address St lucia 4072 Brisbane See on map 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 Other funding € 0,00 INSTITUT PASTEUR France Net EU contribution € 2 284 421,00 Address Rue du docteur roux 25-28 75724 Paris See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations 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 Other funding € 0,00
