Descrizione del progetto
Monitoraggio del monossido di carbonio e della viscosità nelle cellule viventi
Il monossido di carbonio è un gasotrasmettitore endogeno, associato alla citoprotezione e all’omeostasi cellulare. La maggiore produzione enzimatica del monossido di carbonio svolge un ruolo fondamentale nella risoluzione dei processi infiammatori e nell’attenuazione delle malattie cardiovascolari. Le variazioni della viscosità cellulare sono state collegate all’infiammazione, anche nell’ambito delle malattie cardiovascolari. Il movimento controllato dalla diffusione del monossido di carbonio cellulare risente delle variazioni di viscosità. Il progetto COVISENSE, finanziato dall’UE, si propone di effettuare la misurazione simultanea di monossido di carbonio e viscosità cellulare, in relazione allo stato dell’infiammazione e della malattia. I ricercatori introdurranno innovative sonde molecolari bimetalliche al rutenio, che saranno in grado di monitorare sia il monossido di carbonio endogeno che la viscosità dell’ambiente cellulare.
Obiettivo
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.
Campo scientifico
- natural scienceschemical sciencesinorganic chemistryinorganic compounds
- natural scienceschemical sciencesinorganic chemistrytransition metals
- natural sciencesphysical sciencesopticsmicroscopyfluorescence lifetime imaging
- medical and health sciencesclinical medicinecardiologycardiovascular diseases
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
SW7 2AZ LONDON
Regno Unito