Mechanisms of mRNA localisation and cytoskeletal transport
Molecular motors have critical roles in trafficking of organelles, vesicles and macromolecules within the cytoplasm, and aberrant motor function is associated with diseases such as neurodegeneration. Our goal is to understand how motor complexes recognise specific cargoes and deliver them to appropriate regions of the cell. We have a long-standing interest in cytoplasmic transport of messenger RNAs, a process widely used to control where specific proteins operate within cells, but have also become very intrigued by how motors sort other cargos in the nervous system. We use complementary techniques, including Drosophila genetics, in vivo imaging, biochemistry, structural biology and novel single molecule assays of cargo transport in vitro.
Future goals include:
- To understand how the microtubule-based motor dynein recognises specific cargoes and sorts them to their destinations in cells
- To gain insight into how the action of multiple motors bound to a single cargo is orchestrated.
- To elucidate the molecular mechanisms that underpin sorting of specific mRNAs into axons and dendrites in an intact nervous system.
- To understand how transport of cargoes in neurons is regulated by extrinsic cues and how this influences the function of the nervous system.
- Baumbach J., Murthy A.*, McClintock M.A.*, Dix, C.I., Zalyte, R., Hoang, HT., Bullock, SL. (2017)
Lissencephaly-1 is a context-dependent regulator of the human dynein complex.
Elife 6: [Epub ahead of print].
- Mofatteh M. and Bullock S.L. (2017)
SnapShot: Subcellular mRNA localization.
Cell 169: 178-178
- 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.
- Port F. and Bullock S.L. (2016)
Augmenting CRISPR applications in Drosophila with tRNA-flanked sgRNAs.
Nature Methods 13: 852-4 (FP and SB are corresponding authors).
- Schlager M.A*., Hoang H.-T.*, Urnavicius L., Bullock S.L. and Carter A.P. (2014)
In vitro reconstitution of a highly processive recombinant human dynein complex.
EMBO J 33: 1855-1868. (SB and AC are corresponding authors)
- Soundararajan H.C. and Bullock S.L. (2014)
The influence of dynein processivity control, MAPs and microtubule ends on directional movement of a localising mRNA.
eLife 3: e01596.
- Li Jin
- Janina Baumbach
- Mohammad Mofatteh
- Nadine Muschalik
- Mark McClintock
- Vanesa Madan
- David Salvador-Garcia