Regulatory networks controlling persistent lamellipodial protrusion and cancer cell migration.

Matthias Krause (primary)
Randall Centre for Cell and Molecular Biophysics
King's College London
Attila Csikász-Nagy (secondary)
Institute for Mathematical and Molecular Biomedicine and Randall Centre for Cell and Molecular Biophysics
King’s College London

Abstract

Cell migration is essential during development. However, aberrant cell migration causes cancer metastasis. A big question in cell migration research is how persistence of lamellipodia protrusion and cell migration is controlled.
Mesenchymal cells migrate by forming Rac and Arp2/3 controlled lamellipodia, membrane protrusions at the cell front, which protrude and retract.
You will develop mathematical models and use advanced microscopy and CRISPR-Cas9 knockout to study the positive and negative feedback circuits that control Rac and Arp2/3 activity at lamellipodia. You will quantify how these control speed and persistence of lamellipodia and cell migration and use these to refine your model.


References

Cardelli L, Hernansaiz-Ballesteros RD, Dalchau N, Csikász-Nagy A. (2017) Efficient Switches in Biology and Computer Science. PLoS Comput Biol 13(1):e1005100.

Carmona, G., Perera U., Gillett C., Naba A., Law A., Sharma V.P., Wang J., Wyckoff J., Balsamo M., Mosis F., De Piano, M., Monypenny, J., Woodman, N., McConnell, R.E., Mouneimne, G., Van Hemelrijck, M., Cao, Y., Condeelis, J., Hynes, R.O., Gertler, F.B., and Krause M. (2016) Lamellipodin promotes invasive 3D cancer cell migration via regulated interactions with Ena/VASP and SCAR/WAVE, Oncogene, 35(39), 5155-69.

Krause, M. and Gautreau, A. (2014) Steering cell migration: lamellipodium dynamics and the regulation of directional persistence. Nature Reviews Molecular Cell Biology, 15, 577-90.

Law, A., Vehlow, A., Kotini, M., Dodgson, L., Soong, D., Theveneau, E., Bodo, C., Taylor, E., Navarro, C., Perera, U., Michael, M., Dunn, G.A., Bennett, D., Mayor, R., and Krause M. (2013) Lamellipodin and the Scar/WAVE complex cooperate to regulate cell migration in vivo. Journal of Cell Biology, 203(4), 673-689.

Hart, Y. & Alon, U. (2013) The utility of paradoxical components in biological circuits. Mol. Cell 49, 213–21.

Novák, B. & Tyson, J. J. (2008) Design principles of biochemical oscillators. Nat. Rev. Mol. Cell Biol. 9, 981–991.


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
Cell Biology
Techniques & Approaches
BiochemistryImage ProcessingMicroscopy / ElectrophysiologySimulation / Modelling