Website King's College London
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. We have identified NHSL1 as a key regulator of cell migration (Law et al., Nature Communications, 2021)9. NHSL1 is part of the poorly characterized Nance-Horan syndrome protein family. We showed that NHSL1 negatively regulates cell migration via the Scar/WAVE-Arp2/3 complexes which control actin filament nucleation required for cell migration9. Mechanistically, NHSL1 inhibits Scar/WAVE-Arp2/3 activity and consequently lamellipodia stability and cell migration efficiency9. In addition, we observed that NHSL1 localises to vesicles which emanate from the leading edge of migrating cancer cells suggesting that it is involved in vesicle trafficking9. Indeed, recently we showed that NHSL1 interacts with Ena/VASP proteins, key actin cytoskeleton regulators, and promotes fast endophilin-mediated endocytosis1,2. NHSL1 interacts with additional actin effectors (unpublished). During guided migration, growth factor receptors are endocytosed at the leading edge and traffic back there to increase polarity and directional migration. However, the molecular details of the pathways controlling this are still enigmatic.
In this project, which will start in June or October 2026, you will investigate the role of NHSL1 in growth factor receptor recycling supporting directional migration of cancer cells.
You will evaluate how NHSL1 interacts with additional actin effectors. You will use biochemistry to map and Gibson assembly to mutate the binding sites of these additional actin effectors. You will generate CRISPR-knockout cell lines and rescue them and existing NHSL1 CRISPR KO cell lines with cDNA mutated in the binding sites. You will utilise advanced imaging to track and quantify changes in the trafficking of the receptors. You will evaluate the functional significance of these interaction for chemotaxis of cancer cells using a well-established microfluidic chamber and using 3D invasion assays.
Taken together, your PhD work will unravel a novel control mechanism of receptor recycling supporting cancer cell migration.
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 Cell Motility Club.
Funding Notes
Funding for entry in June or 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 in their applications how they intend to fund their studies. We prefer candidates that have secured or wish to secure their own competitive funding from overseas government agencies.
If you are interested in this PhD project, please e-mail me (Matthias.Krause (at) KCL.AC.UK) with your CV and transcripts and indicate how you plan to fund your studies.
References
1. 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
2. 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
3. Casamento, A., and Boucrot, E., (2020) Molecular mechanism of Fast Endophilin-Mediated Endocytosis. Biochemical Journal, 477, 2327-2345.
4. 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.
5. 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.
6. 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.
7. 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).
8. 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.
9. 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.
10. 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
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