Investigate the molecular mechanism controlling FEME (Fast Endophilin Mediated Endocytosis) in cancer cell migration using CRISPR, biochemistry, and advanced microscopy methods.

About the Project

Cancer is a devastating disease: more than one in three people in the UK will develop cancer in their lifetime. Metastasis is the primary cause of cancer related deaths. Metastasis is caused by aberrant cell migration of cancer cells. Endocytosis is an essential process during development and tissue homeostasis ensuring diverse functions including modulation of growth factor signalling. Growth factor-receptor signalling such as the epidermal growth factor receptor (EGFR) controls proliferation as well as directed migration including cancer cell migration. We have shown that the protein Lamellipodin (Lpd) cooperates with the protein endophilin to promote clathrin-mediated EGFR endocytosis (Vehlow et al., EMBO J. 2013) and cancer cell migration through the actin regulatory Ena/VASP proteins and the Scar/WAVE complex (Law et al., Journal of Cell Biology, 2013; Carmona et al., Oncogene, 2016). In addition, Lpd recruits endophilin to the leading edge of cells thereby inducing clathrin-independent endocytosis (Fast, Endophilin-Mediated Endocytosis (FEME)) and some regulations of FEME have been explored (Boucrot et al., Nature, 2015; Wah-Hak et al., Nature cell Biology, 2018; Casamento and Boucrot, Biochem. J., 2020). However, we still do not understand the fundamental mechanism of FEME. Actin polymerisation is essential for FEME and may provide the force for invagination and scission, but we do not how actin polymerisation is controlled to mediate FEME and its integration with membrane bending BAR domain containing proteins.

In this project, which will start in October 2026, you will investigate the molecular mechanisms of how actin polymerisation contributes to FEME. Our hypothesis is that this is mediated by Lpd, Ena/VASP proteins, the Scar/WAVE complex, and additional actin regulators. In addition to Lpd, we already identified another key protein, NHSL1 mediating FEME which links to actin regulators.

You will generate CRISPR-knockout cell lines and rescue them with cDNA mutated in the binding sites. You will characterize resultant cell lines by super-resolution live cell microscopy methods for defects/efficiency in FEME. You will also generate mStaygold/mScarlet knock-in cell lines for evaluating timing of FEME using TIRF and/or super-resolution live cell imaging. You will use biochemical ELISA-based endocytosis assays to quantify EGFR uptake.

Taken together, your PhD work will unravel a novel and general control mechanism of FEME endocytosis in migrating cancer cells.

You will join a friendly, interactive lab, which is part of the Cellular Biophysics Section of the Randall Centre at King’s College London: 11 laboratories with shared interest in the regulation of the cytoskeleton in cell division, adhesion, migration, and intracellular trafficking with joint meetings. Furthermore, our lab is part of the UK wide UK Cell Motility Club which I am organising.

Funding Notes

Funding for entry in October 2026: Only self-funded students are eligible. Candidates must possess or be expected to achieve a 1st or upper 2nd class degree in a relevant subject of the biosciences. All applicants should indicate how they intend to fund their studies. We prefer candidates who have secured or wish to secure competitive funding from overseas government agencies.

If you are interested in this project, please e-mail me (Matthias.Krause at KCL.AC.UK) with your CV and transcripts indicating how you plan to fund your studies.

References

Selected relevant publications:
1. Sheng-yuan Wu, Marcela M. Moreno, Anna Noble, Amirul Haziq Azwan, Matthew Guille, Karen J. Liu, Matthias Krause (2025) The Actin regulator Mena promotes Wnt signalosome endocytosis and Wnt signalling. https://www.biorxiv.org/content/10.1101/2025.11.24.690281v1
2. Cope, J.F.W., Law, A.-L., Juma, S., Sharpe, H.J., and Krause M. (2025) Nance-Horan Syndrome-like 1 interacts with endophilin and Ena/VASP proteins to promote fast endophilin-mediated endocytosis. BioRxiv, https://www.biorxiv.org/content/10.1101/2024.10.23.619882v3
3. Narayan, K.B., James, H.P., Cope, J., Mondal, S., Baeyens, L., Milano, F., Zheng, J., Krause, M., and Baumgart, T. (2025) VASP phase separation with priming proteins of fast endophilin mediated endocytosis modulates actin polymerization. Journal of Biological Chemistry, DOI: 10.1016/j.jbc.2025.110834
4. Casamento, A., and Boucrot, E., (2020) Molecular mechanism of Fast Endophilin-Mediated Endocytosis. Biochemical Journal, 477, 2327-2345.
5. Wah Hak, L.C., Khan, S., Di Meglio, I., Law, A.-L., Häsler, S.L.A., Quintaneiro, L., Ferreira, A., Krause, M., McMahon, H., and Boucrot, E. (2018). FBP17 and CIP4 recruit SHIP2 and Lamellipodin to prime the plasma membrane for Fast Endophilin-Mediated Endocytosis. Nature Cell Biology, 20, 1023-1031.
6. Carmona G, Perera U, Gillett C, Naba A, Law AL, Sharma VP, Wang J, Wyckoff J, Balsamo M, Mosis F, De Piano M, Monypenny J, Woodman N, McConnell RE, Mouneimne G, Van Hemelrijck M, Cao Y, Condeelis J, Hynes RO, Gertler FB, Krause M. (2016) Lamellipodin promotes invasive 3D cancer cell migration via regulated interactions with Ena/VASP and SCAR/WAVE. Oncogene. 2016 Sep 29;35(39):5155-69.
7. Boucrot, E., Ferreira, A.P.A., Almeida-Souza, L., Debard, S., Vallis, Y., Howard, G., Bertot, L., Sauvonnet, N., and McMahon, H.T. (2015) Endophilin marks and controls a clathrin-independent endocytic pathway. Nature, 517, 7535, 460-465.
8. 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 (2014).
9. Vehlow, A., Soong, D., Vizcay-Barrena, G., Bodo, C., Law, A., Perera, U., and Krause, M. (2013) Endophilin, Lamellipodin, and Mena Cooperate to Regulate F-actin-dependent Endocytosis of the EGF-receptor. EMBO J. 32, 2722-2734.
10. 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.
11. Law, A.-L., Jalal, S., Pallett, T., Mosis, M., Guni, A., Brayford, S., Yolland, L., Marcotti, S., Levitt. J.A., Poland, S.P., Rowe-Sampson, M., Jandke, A., Köchl, R., Pula, G., Ameer-Beg, S.M., Stramer, B.M., and Krause, M. (2021) Nance-Horan Syndrome-like 1 protein negatively regulates Scar/WAVE-Arp2/3 activity and inhibits lamellipodia stability and cell migration. Nature Communications, 12(1): 5687.
12. Dobson, L., Barrell, W.B., Seraj, Z., Lynham, S., Wu, S., Krause, M.*, Liu, K.J.*, (2023) GSK3 and Lamellipodin balance lamellipodial protrusions and focal adhesion maturation in mouse neural crest migration. Cell Reports, 42(9). *Co-senior authors