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Dissecting the mechanism of the regulation of γTuRC-mediated microtubule nucleation

Project description

Mechanistic insight into cytoskeleton regulation

The microtubule cytoskeleton plays an important role in cell architecture and function. Microtubule nucleation is a regulated process governed by the γ-tubulin ring complex (γTuRC). The scope of the EU-funded TuRCreg project is to dissect the molecular mechanism of γTuRC-mediated nucleation using recent technological advancements in biochemistry, microscopy, and structural biology. The project's results will provide fundamental information on the cytoskeletal organisation and dynamics in cells and help scientists understand how the microtubule cytoskeleton is implicated in certain diseases. Long-term project results will pave the way for the identification of novel therapeutic targets.

Objective

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.

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Coordinator

FUNDACIO CENTRE DE REGULACIO GENOMICA
Net EU contribution
€ 160 932,48
Address
Carrer doctor aiguader 88
08003 Barcelona
Spain

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
Links
Other funding
€ 0,00