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Motor proteins: from structural biology to human disease


   Sir William Dunn School of Pathology

  Dr Anthony Roberts  Friday, December 09, 2022  Competition Funded PhD Project (Students Worldwide)

About the Project

Dynein and kinesin are families of motor proteins that use ATP hydrolysis to transport cellular components and signalling molecules along the microtubule cytoskeleton. Dynein and kinesin also have critical roles in assembling larger cellular structures, such as the mitotic spindle, cilia and flagella. Our current goals are to understand how dynein and kinesin work together to form bidirectional transport systems [1,2] and how the motors selectively attach to cargoes [3]. We are studying these questions using transport within cilia and flagella as a biomedically important model [4]. Defective transport in cilia causes a variety of human disorders associated with vision impairment, skeletal abnormalities, cystic kidneys, and infertility, among other conditions. In this project, you will learn cryo-electron microscopy (cryo-EM), purification of multi-protein complexes, and cell biology techniques to advance understanding of motor proteins in health and disease.


Funding Notes

4 Year DPhil Prize Studentships cover University fees, a tax free stipend of ~£20,168 pa, and up to £5,300 pa for research costs and travel. The competition is open to applicants from all countries. See View Website for full details and to apply.

References

1] Toropova K, Zalyte R, Mukhopadhyay AG, Mladenov M, Carter AP, Roberts AJ (2019) Structure of the Dynein-2 Complex and its Assembly with Intraflagellar Transport Trains. Nature Structural & Molecular Biology.
[2] Toropova K, Zalyte R, Mukhopadhyay AG, Mladenov M, Carter AP, Roberts AJ (2017) Intraflagellar Transport Dynein is Autoinhibited by Trapping of its Mechanical and Track-binding Elements. Nature Structural & Molecular Biology.
[3] IFT-A Structure Reveals Carriages for Membrane Protein Transport into Cilia (2022) Hesketh SJ, Mukhopadhyay AG, Nakamura D, Toropova K, Roberts AJ. bioRxiv https://doi.org/10.1101/2022.08.09.503213
[4] Webb S, Mukhopadhyay AG, Roberts AJ (2020) Intraflagellar Transport Trains and Motors: Insights from Structure. Seminars in Cell & Developmental Biology.

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