Description du projet
Monoxyde de carbone et surveillance de la viscosité dans les cellules vivantes
Le monoxyde de carbone (CO) est un gazotransmetteur endogène, associé à la cytoprotection et à l’homéostasie cellulaire. La production enzymatique accrue de CO joue un rôle crucial dans la résolution des processus inflammatoires et l’atténuation des troubles cardiovasculaires. Les changements au niveau de la viscosité cellulaire ont été liés à l’inflammation, notamment dans les maladies cardiovasculaires. Le mouvement contrôlé par diffusion des cellules de monoxyde de carbone est influencé par ces changements de viscosité. Le projet COVISENSE, financé par l’UE, entend effectuer des mesures simultanées du monoxyde de carbone et de la viscosité cellulaire en lien avec l’état d’inflammation et de la maladie. Les chercheurs dévoileront des sondes moléculaires de ruthénium bimétalliques innovantes capables de surveiller à la fois le monoxyde de carbone endogène et la viscosité dans l’environnement cellulaire.
Objectif
Despite its toxic reputation, carbon monoxide (CO) is also an important biological messenger molecule that regulates many vital cell processes, including the response to disease. Increased enzymatic generation of carbon monoxide plays a critical role in the resolution of inflammatory processes and alleviation of cardiovascular disorders. At the same time, altered viscosity levels have been associated with inflammation, including in cardiovascular disease. Since the diffusion-controlled movement of carbon monoxide is also affected by changes in the viscosity of the cellular environment, the two aspects are intimately connected. Therefore, the simultaneous measurement of both carbon monoxide and cellular viscosity would provide unprecedented information on the functioning of the cell and the state of inflammation and disease. We propose to achieve this through a new family of bimetallic ruthenium(II) molecular probes capable of monitoring both endogenous carbon monoxide (using fluorescence intensity) and the viscosity in the cellular environment (through fluorescence lifetime). These highly selective probes would show very low detection limits for CO and operate within the ‘biological window’ above 650 nm. At the same time, internal rotation of the BODIPY fluorophore would allow fluorescence lifetime imaging microscopy (FLIM) to be used to monitor the local viscosity. Through a collaboration with immune-oncologists, the probes will be used to expand the understanding of the role played by the enzyme, haem oxygenase (HO-1), that produces CO. This could help illuminate the association between HO-1 expression and poor prognosis in cancer patients. The project will combine ligand design, organometallic synthesis, fluorescence imaging and cell work, providing the opportunity to gain experience in a range of areas related to sensing in biological environments.
Champ scientifique
- natural scienceschemical sciencesinorganic chemistryinorganic compounds
- natural scienceschemical sciencesinorganic chemistrytransition metals
- natural sciencesphysical sciencesopticsmicroscopyfluorescence lifetime imaging
- medical and health sciencesclinical medicinecardiologycardiovascular diseases
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Mots‑clés
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
SW7 2AZ LONDON
Royaume-Uni