Subcellular mRNA localisation is a prevalent mechanism for controlling where proteins operate within cells and underpins many crucial biological functions, from embryonic patterning to synaptic plasticity. Disruption of mRNA trafficking has been linked to neurodevelopmental and neurodegenerative disorders, as well as cancer metastasis. Thus, studies of mRNA localisation not only deepen our understanding of fundamental cell biology but also offer potential routes to novel therapeutic strategies.
The goal of this PhD project is to uncover new molecular mechanisms that govern mRNA localisation and to elucidate how they contribute to specialised cellular functions. Our group has established tractable systems for studying mRNA trafficking in Drosophila and human cells, leading to the discovery of novel factors that either recruit mRNAs to molecular motors or modulate motor dynamics along cytoskeletal tracks. The next major step – and the focus of this project – is to understand how these factors function at the molecular level, both individually and in co-ordination with each other and the ribosome, to affect local translation across different cell types. This will involve dissecting molecular interactions through a combination of in vitro reconstitution and cell-based approaches, alongside functional studies in polarised cells such as oocytes, epithelia, and neurons.
The project is expected to combine biochemistry, single-molecule imaging of mRNA transport (in cells and in vitro motility assays), transcriptomics, and stem-cell derived neuronal and organoid models. There is also an option to collaborate with Andrew Carter’s group at LMB to develop a structural understanding of the mRNA transport machinery. Please see our website for further information.
The exact project will be defined in collaboration with the successful applicant, based on their interests. The position would suit a student who is excited by multi-disciplinary research and keen to contribute to a dynamic and supportive research environment.
References
Cryo-EM structures of Egl–BicD–RNA complexes reveal how diverse mRNAs are selected for subcellular localization
bioRxiv: (2025) preprint
Tropomyosin 1-I/C coordinates kinesin-1 and dynein motors during oskar mRNA transport
Nature Structural & Molecular Biology 31(3): 476-488 (2024)
Intracellular mRNA transport and localized translation.
Nat Rev Mol Cell Biol 22(7): 483-504 (2021)
SnapShot: Subcellular mRNA Localization
Cell 169(1): 178-178.e1 (2017)