architecture of IFT trains that enter cilia. However, the molecular basis by which ciliary dyneins, particularly the force generating outer dynein arms (ODAs), attach to IFT trains remains poorly resolved.
ODA transport requires packaging and inhibition by DNAAF9 (Shulin). Our most recent study suggests that Shulin not only inhibits ODAs but may also aid their attachment to the IFT system. This PhD project aims to build on our ongoing studies to elucidate the molecular mechanism of ODA motor attachment to IFT trains. The project will use an integrative cellular and structural biology approach combining biochemical reconstitutions, single-particle EM, protein structure modeling using AlphaFold and ultrastructure expansion microscopy (U-ExM).
Funding Notes
4 Year PhD Prize Studentships cover full University fees, a tax free enhanced stipend of ~£24,305 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
Housseini, K. et al., DNAAF9 (Shulin) and ARL3 regulate the transport and activation of ciliary Outer Dynein Arms (ODAs). BioRxiv preprint 2024.08.15.608058 (2024). DOI:10.1101/2024.08.15.608058.
Lacey, S. E., Foster, H. E. & Pigino, G. The molecular structure of IFT-A and IFT-B in anterograde intraflagellar transport trains. Nat. Struct. Mol. Biol. 2023 305 30, 584–593 1025 (2023). DOI: 10.1038/s41594-022-00905-5
Hesketh, S. J., Mukhopadhyay, A. G. et al., IFT-A structure reveals carriages for membrane protein transport into cilia. Cell. 2022 Dec 22;185(26):4971-4985.e16. DOI: 10.1016/j.cell.2022.11.010
Mali, G. R., Lau, C. L., Abid Ali, F et al., Shulin packages axonemal outer dynein arms for ciliary targeting. Science. 2021 Feb 371 (6532), 910–916. DOI: 10.1126/science.abe0526
