Nanoscale dissection of the Ephrin-Eph Receptor signalling axis in cellular invasion

Prof. Richard Grose (primary)
Centre for Tumour Biology, Barts Cancer Institute
Queen Mary University of London
Dr Sabrina Simoncelli (secondary)
Chemistry and London Centre for Nanotechnology
University College London

Abstract

Juxtacrine cellular cross-talk is critical during development, allowing leader and follower cells to communicate during angiogenesis and neuronal migration. One key axis mediating this process is Ephrin-Eph receptor signalling. Ephrin ligands induce forward signalling in neighbouring cells expressing Eph receptor tyrosine kinases, but also exhibit reverse signalling within the Ephrin-expressing cell. As with many developmental pathways, this signalling is recapitulated in disease, for example in pancreatic cancer invasion. We will use genetic engineering and super-resolution microscopy, in 2D/3D cell-based models to interrogate the dynamics of this reverse signalling, providing crucial insights into the regulation and function of this signalling axis.


References

1. Adams SD, Csere J, D’angelo G, Carter EP, Romao M, Arnandis T, Dodel M, Kocher HM, Grose R, Raposo G, Mardakheh F, Godinho SA. Centrosome amplification mediates small extracellular vesicle secretion via lysosome disruption. Current Biology. S0960-9822(21)00061-0. 2021.

2. Coleman SJ, Chioni A-M, Ghallab M, Anderson RK, Lemoine NR, Kocher HM, Grose R. Pancreatic cancer cell invasion is mediated by nuclear translocation of FGFR1 and FGF2 in stellate cells. EMBO Molecular Medicine. 6:467-481. 2014.

3. Simoncelli S, Griffié J, Williamson DJ, Bibby J, Bray C, Zamoyska R, Cope AP, Owen DM. Multi-colour DNA qPAINT reveals how Csk nano-clusters regulate T-cell receptor signalling. Cell Reports, 33, 108523, 2020.

4. Williamson DJ, Burn GL, Simoncelli S, Griffié J, Peters R, Davis DM, Owen DM. Machine learning for cluster analysis of localization microscopy data. Nature Communications, 11, 1493, 2020.

5. Dravis C & Henkemeyer M*. Ephrin-B reverse signaling controls septation events at the embryonic midline through separate tyrosine phosphorylation-independent signaling avenues. Developmental Biology. 355, 138–151. 2011. (*Prof Henkemeyer is collaborating on this project, supplying Ephrin constructs and novel agents, but will not be part of the supervisory team)


BBSRC Area
Molecules, cells and industrial biotechnology
Area of Biology
Cell BiologyDevelopment
Techniques & Approaches
BiochemistryChemistryImage ProcessingMicroscopy / ElectrophysiologyMolecular BiologySimulation / Modelling