Microtubule motors organise cells by powering the movement of organelles, vesicles and macromolecules through the cytoplasm. Elucidating how motor complexes operate is not just valuable for understanding fundamental cell biology – there is also clear disease relevance. Impaired cargo transport is increasingly implicated in neurodegenerative disorders, and infection by many pathogenic viruses depends on their translocation by microtubule motors.
Our goal is to understand how motors recognise their diverse cargoes, how movement of motor complexes is orchestrated in cells, and the links between defective transport processes and neurological diseases. We have a long-standing interest in mRNA targeting within the cytoplasm, a process that plays critical roles in the spatial control of protein function in many cell types.
We combine single-molecule analysis of reconstituted transport complexes in vitro with mechanistic dissection in human cells (including iPS cell-derived neurons) and Drosophila using genetics and advanced imaging. We also collaborate with Andrew Carter’s group at LMB to develop a structural understanding of transport processes. Please see our website for further information.
Potential PhD projects include:
(i) Mechanistic analysis of novel interactors and regulators of the dynein motor, which we recently identified in large-scale biochemical and CRISPR screens
(ii) Elucidating how dynein and kinesin motors orchestrate subcellular localisation of specific mRNAs in human cells or Drosophila oocytes.
The project will be decided together with the successful applicant based on their interests. The position would suit a student who is excited about multi-disciplinary research and would enjoy working in a highly supportive and dynamic group.
References
Wong C.H., Wingett S.W., Qian C., Taliaferro J.M., Ross-Thriepland D.* and Bullock S.L.* (2023) Genome-scale requirements for dynein-based trafficking revealed by a high-content arrayed CRISPR screen. bioRxiv2023.03.01.530592 (* joint senior authors)
Madan V., Albacete Albacete L., Jin L., Scaturro P., Watson J.L., Muschalik N., Begum F., Boulanger J., Bauer K., Kiebler M.A., Derivery E. and Bullock S.L. (2023) HEATR5B associates with dynein-dynactin and selectively promotes motility of endosomal membranes. EMBO Journal, e114473.
McClintock M.A., Dix C.I., Johnson C.M., McLaughlin S.H., Maizels R.J., Hoang, H.-T. and Bullock S.L. (2018) RNA-directed activation of cytoplasmic dynein-1 in reconstituted transport RNPs. eLIFE 7: doi: 10.7554/eLife.36312
Reck-Peterson S.L., Redwine W.B., Vale R.D., Carter A.P. (2018) The cytoplasmic dynein transport machinery and its many cargoes. Nat Rev Mol Cell Biol, 19: 382-398.
Mofatteh M. and Bullock S.L. (2017) Snapshot: Subcellular mRNA localization. Cell, 169:178.