Projektbeschreibung
Mechanistische Einblicke in die Zytoskelettregulierung
Das aus Mikrotubuli bestehende Zytoskelett spielt eine wichtige Rolle für die Architektur der Zelle und ihre Funktion. Die Nukleation der Mikrotubuli ist ein regulierter Prozess, der durch den γ-Tubulin-Ringkomplex (γTuRC) gesteuert wird. Das EU-finanzierte Projekt TuRCreg bezweckt, den molekularen Mechanismus der γTuRC-vermittelten Nukleation mithilfe der neuesten technologischen Fortschritte der Biochemie, Mikroskopie und Strukturbiologie zu analysieren. Die Projektergebnisse werden grundlegende Informationen über Organisation und Dynamik des Zytoskeletts in den Zellen liefern. Anhand derer wird die Wissenschaft die Rolle des Mikrotubulus-Zytoskelett bei bestimmten Krankheiten besser verstehen. Langfristig werden die Projektergebnisse neuartige therapeutische Zielstrukturen erkennen lassen.
Ziel
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.
Wissenschaftliches Gebiet
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MSCA-IF-EF-ST - Standard EFKoordinator
08003 Barcelona
Spanien