Descrizione del progetto
Migliorare la comprensione dell’elaborazione dei segnali biologici
L’elaborazione dei segnali biologici svolge un ruolo fondamentale nel funzionamento di vari organismi viventi, in particolare in processi cruciali come la divisione cellulare e la lotta alle malattie che colpiscono l’organismo. Pertanto, una comprensione più approfondita e un migliore controllo di questo fenomeno rivestono un’immensa importanza per il futuro dei settori e delle industrie interessate. Il progetto Phosphoprocessors, finanziato dal CER, intende basarsi sugli studi precedenti dei membri del gruppo di ricerca sulla fosforilazione multisito e approfondire l’intricato funzionamento delle chinasi ciclina-dipendenti. Conducendo test rigorosi, l’obiettivo finale è quello di ottenere una comprensione più completa e argomentabile della sequenzialità degli eventi del ciclo cellulare.
Obiettivo
Multisite phosphorylation of proteins is a powerful signal processing mechanism playing crucial roles in cell division and differentiation as well as in disease. Our goal in this application is to elucidate the molecular basis of this important mechanism. We recently demonstrated a novel phenomenon of multisite phosphorylation in cell cycle regulation. We showed that cyclin-dependent kinase (CDK)-dependent multisite phosphorylation of a crucial substrate is performed semiprocessively in the N-to-C terminal direction along the disordered protein. The process is controlled by key parameters including the distance between phosphorylation sites, the distribution of serines and threonines in sites, and the position of docking motifs. According to our model, linear patterns of phosphorylation networks along the disordered protein segments determine the net phosphorylation rate of the protein. This concept provides a new interpretation of CDK signal processing, and it can explain how the temporal order of cell cycle events is achieved. The goals of this study are: 1) We will seek proof of the model by rewiring the patterns of budding yeast Cdk1 multisite networks according to the rules we have identified, so to change the order of cell cycle events. Next, we will restore the order by alternative wiring of the same switches; 2) To apply the proposed model in the context of different kinases and complex substrate arrangements, we will study the Cdk1-dependent multisite phosphorylation of kinetochore components, to understand the phospho-regulation of kinetochore formation, microtubule attachment and error correction; 3) We will apply multisite phosphorylation to design circuits for synthetic biology. A toolbox of synthetic parts based on multisite phosphorylation would revolutionize the field since the fast time scales and wide combinatorial possibilities.
Campo scientifico
- natural sciencesbiological sciencessynthetic biology
- engineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsignal processing
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesphysical sciencesopticsmicroscopy
- natural scienceschemical sciencesorganic chemistryamines
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-COG - Consolidator GrantIstituzione ospitante
51005 Tartu
Estonia