Simon Bullock

Shedding light on microtubule-based cargo transport in vitro and in vivo
Group Leader page

Microtubule-based transport plays critical roles in the distribution and sorting of cellular components and pathogens. The importance of this process is underlined by the discovery that mutations in microtubule motor proteins and their co-factors cause neurodevelopmental and neurodegenerative diseases.

The primary goal of the group is to elucidate how microtubule-based cargo transport is controlled in time and space. We have a long-standing interest in how mRNAs are sorted to specific locations by molecular motors but have also become fascinated by the transport of other cargoes.

We use a range of techniques, including biochemistry, single molecule imaging of in vitro reconstituted transport complexes, and visualisation of transport in a living organism (using Drosophila as a tractable model). We have developed highly efficient CRISPR genome engineering tools for Drosophila and are applying these to several projects.

The PhD project is likely to focus on one of the following questions: (1) how are dynein and kinesin motors linked to specific cargoes and how is this process regulated in the cell; (2) how do multiple motor complexes co-operate on a single cargo; (3) how are large RNP granules, containing multiple mRNA molecules, assembled and how are they trafficked in the cytoplasm? The precise project will be decided together with the successful applicant based on their interests.

We are seeking a student who is enthusiastic and enjoys working in an interactive environment.

Please see our website for further information.


References

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. e36312.

Vagnoni A. and Bullock S.L. (2018)
A cAMP/PKA/kinesin-1 axis promotes the axonal transport of mitochondria in aging Drosophilaneurons.
Curr Biol., 28: 1265-1272.

Baumbach J., Murthy A., McClintock M.A., Dix, C.I., Zalyte R., Hoang H.T., Bullock S.L. (2017)
Lissencephaly-1 is a context-dependent regulator of the human dynein complex.
eLife, 6: e21768.

Hoang H.T., Schlager M.A., Carter A.P. and Bullock S.L. (2017)
DYNC1H1 mutations associated with neurological diseases compromise processivity of dynein-dynactin-cargo adaptor complexes.
PNAS, 114: E1597-E1606.

Mofatteh, M. and Bullock S.L. (2017)
Snapshot: Subcellular mRNA localization.
Cell, 169:178.

Port, F. and Bullock, S.L.  (2016)
Augmenting CRISPR applications in Drosophila with tRNA-flanked sgRNAs.
Nature Methods, 13:852-854.