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Seeing the centre of the cytoskeleton network


Faculty of Biological Sciences

About the Project

This project uses super-resolution and cryo-electron microscopy to address how the cell organises multiple intra-cellular activities.

Inside the cell, the specific action of proteins is regulated in time and space, enabling the cell to work as one tiny machine. The cytoskeleton, comprising microtubules, actin filaments and intermediate filaments, is key for spatial and temporal organisation of proteins and is the essential framework of the cell. The centrosome is an important organelle that functions as the central hub of the filament network. It is well known as the main microtubule-organising centre in animal cells, is mainly comprised of microtubules and associated proteins and it nucleates and organises microtubules in interphase and dividing cells, as well as in primary cilia. It was recently discovered that the centrosome can also nucleate actin filaments. However we do not know how actin filaments interact with centrosomes, and how this interaction affects cellular activities.

To answer these questions, the student will use cellular and structural biology techniques to visualise how actin filaments interact with centrosomes, which proteins are important for this, and how this organisation varies with the cell cycle, and in primary cilia, and test their hypotheses by manipulating this interaction.

Funding Notes

White Rose BBSRC Doctoral Training Partnership in Mechanistic Biology
4 year fully-funded integrated research and skills training programme, starting October 2021:
• Research Council Stipend (estimated £15,600 per year)
• Tuition fees at the UK fee rate (£4,473 per year)
• Research training and support grant

Please note: international tuition fees for 2021 entry are £23,750

Not all projects will be funded; the DTP will appoint a limited number of candidates via a competitive process.

Requirements:
At least a 2:1 honours degree or equivalent. We welcome students with biological, chemical or physical sciences, or
mathematical backgrounds interested in biological questions.

References

Ochi, T., Quarantotti, V., Lin, H., Jullien, J., Boselli F., Barnabas, D., Silve, I. R. Johnson, C., McLaughlin, S., Feund, S., Blackford, A., Kimata, Goldstein, R. E., Y., Jackson, S. P., Blundell, T. L., Dutcher, S. K., Gergely, F., and Breugel, M. V. (2020). CCDC61/VFL3 is a paralog of SAS6 and promotes ciliary functions. Structure, 28, 674-689.

Burgess SG, Mukherjee M, Sabir S, Joseph N, Gutiérrez-Caballero C, Richards MW, Huguenin-Dezot N, Chin JW, Kennedy EJ, Pfuhl M, Royle SJ, Gergely F, Bayliss R (2018) Mitotic spindle association of TACC3 requires Aurora-A-dependent stabilization of a cryptic α-helix. EMBO J. 37: e97902

Lopata, A., Hughes, R., Tiede, C., Heissler, S. M., Sellers, J. R., Knight, P. J., Tomlinson, D., and Peckham, M. (2018) Affimer proteins for F-actin: novel affinity reagents that label F-actin in live and fixed cells. Sci Rep 8, 6572

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