Descripción del proyecto
Ampliar los conocimientos sobre el procesamiento de señales biológicas
El procesamiento de señales biológicas desempeña un papel vital en el funcionamiento de diversos organismos vivos, sobre todo en procesos cruciales como la división celular y la lucha contra enfermedades que afectan al organismo. Por lo tanto, comprender y controlar mejor este fenómeno reviste una enorme importancia para el futuro de los sectores e industrias pertinentes. En el proyecto Phosphoprocessors, financiado por el Consejo Europeo de Investigación, se pretende aprovechar las investigaciones previas de los miembros de su equipo sobre la fosforilación multisitio y profundizar en el intrincado funcionamiento de las cinasas dependientes de ciclinas. Mediante la realización de pruebas rigurosas, su objetivo principal es ampliar y justificar la aparición secuencial de los acontecimientos del ciclo celular.
Objetivo
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.
Ámbito científico
- natural sciencesbiological sciencessynthetic biology
- engineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsignal processing
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesphysical sciencesopticsmicroscopy
- natural scienceschemical sciencesorganic chemistryamines
Programa(s)
Régimen de financiación
ERC-COG - Consolidator GrantInstitución de acogida
51005 Tartu
Estonia