TuRCreg · Dissecting the mechanism of the regulation of γTuRC-mediated microtubule nucleation
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2022-09-01 → 2024-08-31
- EU contribution
- €160,932
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Dissecting the mechanism of the regulation of γTuRC-mediated microtubule nucleation
Cells depend on a network of structures called microtubules for division, transport, and shape maintenance. Proper microtubule organization requires tight regulation of their assembly, known as microtubule nucleation, which is driven by the γ-tubulin ring complex (γTuRC). Disruptions in γTuRC activity can contribute to diseases like cancer or neurodegenerative disorders. Our research aimed to uncover how γTuRC activates microtubule formation. Using advanced biochemistry, microscopy, and structural studies, we explored how regulatory factors enhance γTuRC activity and change its shape to promote microtubule growth. The findings revealed that γTuRC undergoes structural changes to form a precise template for microtubule assembly, challenging traditional views. This insight could guide new treatments targeting γTuRC to control cell division in cancer or stabilize microtubules in neurodegenerative diseases, laying a foundation for future research on health issues related to microtubule regulation.
Data: CORDIS, © European Union
Project 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.
Original text from CORDIS.
Participants
- FUNDACIO CENTRE DE REGULACIO GENOMICA · BarcelonaCoordinatorSpain
Links
Data: CORDIS, © European Union