Description du projet
Aperçu mécanistique de la régulation du cytosquelette
Le cytosquelette des microtubules joue un rôle important dans l’architecture et la fonction des cellules. La nucléation des microtubules est un processus régulé par le complexe annulaire de la γ-tubuline (γTuRC). Le projet TuRCreg, financé par l’UE, entend disséquer le mécanisme moléculaire de la nucléation induite par le γTuRC en utilisant les récentes avancées technologiques en biochimie, en microscopie et en biologie structurale. Les résultats du projet fourniront des informations fondamentales sur l’organisation et la dynamique du cytosquelette dans les cellules et aideront les scientifiques à comprendre comment le cytosquelette des microtubules est impliqué dans certaines maladies. Les résultats du projet à long terme ouvriront la voie à l’identification de nouvelles cibles thérapeutiques.
Objectif
Cells regulate the nucleation of microtubule polymerization locally and temporally, which is translated into accurate organization of the microtubule cytoskeleton, crucial for proper cell function. It is well established that the major microtubule nucleator in animal cells, the γ-tubulin ring complex (γTuRC), is central for such regulation and its implication in disease is clear. However, for more than 20 years, nobody was able to dissect the molecular mechanism of microtubule nucleation by γTuRC, a current big question in the microtubule area of research. Now, this project will make this challenge achievable by taking advantage of very recent technological advancements in the microtubule field. Aiming to dissect the molecular mechanism of γTuRC-mediated nucleation, the work here proposed will pioneer the reconstitution of physiological microtubule nucleation by γTuRC, using an original combination of biochemistry, single molecule microscopy and structural biology approaches. This will contribute to the progress in understanding microtubule organization and dynamics in cells, and will open new perspectives to explore further the molecular mechanisms behind the diseases associated to γTuRC and γTuRC-associated proteins (e.g. neurological conditions and cancer). This proposal will not just accomplish the current challenges in the cytoskeletal field as will serve as the basis to understand and possibly treat such diseases, which are included on the European Union research priorities regarding the Horizon 2020 program. The creative and innovative nature of this project will also place myself, the host lab and the Institute where the project will be developed, and the EU in the forefront of research in the microtubule cytoskeletal field, contributing to my main goal in becoming a leader in molecular and cell biology of the cytoskeleton, in Europe.
Champ scientifique
Programme(s)
Régime de financement
MSCA-IF-EF-ST - Standard EFCoordinateur
08003 Barcelona
Espagne