Website King's College London
About the Project
Cancer and Wnt signaling: Cancer is a devastating disease affecting more than one in three people in the UK during their lifetime. Over 90% of colorectal cancers involve inappropriate activation of Wnt signaling, a fundamental pathway that controls when cells divide, differentiate, or die. Understanding how Wnt signaling is regulated is crucial for developing better cancer treatments with fewer side effects than current therapies.
The scientific challenge: When Wnt molecules bind to their receptors (Frizzled and LRP5/6) on the cell surface, they cluster into structures called “signalosomes” that activate the pathway. Recent discoveries reveal these signalosomes are remarkably small and transient yet somehow generate sustained cellular responses lasting hours. This paradox—how brief receptor interactions produce prolonged signaling—represents one of the most significant unresolved questions in the field. Different studies have proposed conflicting mechanisms involving direct inhibition or various endocytic pathways, but the true mechanism remains unknown.
Our research focus: We have identified potential links between actin cytoskeletal regulators and Wnt receptor signaling. Our data suggest these proteins may play a previously unrecognized role in regulating Wnt signaling through effects on receptor trafficking and localization. We hypothesize that cytoskeletal proteins facilitate receptor endocytosis and enabling sustained pathway activation beyond initial plasma membrane signaling events.
What you will do: In this interdisciplinary project starting in June or October 2026, you will:
· Investigate receptor endocytosis: Use CRISPR-Cas9 genome editing and advanced live-cell imaging techniques to study how Wnt receptors are internalized at physiologically relevant concentrations. You will determine which endocytic pathways are involved and evaluate the role of actin cytoskeletal regulators in this process.
· Map spatial signaling: Employ fluorescent biosensors and super-resolution microscopy to determine where in the cell Wnt signaling is activated and sustained. You will use biochemical approaches to analyze signaling from different cellular compartments.
· Quantify signaling outputs: Use reporter assays and protein analysis to measure how cytoskeletal-receptor interactions affect Wnt pathway activation. You will test the functional significance of these interactions using knockout and rescue approaches.
· Validate in developing embryos: Perform experiments in Xenopus embryos using live imaging and functional assays to assess the physiological importance of these regulatory mechanisms during development.
Impact and outcomes: Your work will identify actin cytoskeletal proteins as potential therapeutic targets for Wnt-driven cancers affecting millions globally. Unlike essential Wnt pathway components, these modulators may offer therapeutic windows for cancer-specific intervention with reduced side effects. Beyond cancer, this research will impact regenerative medicine by revealing how cytoskeletal control regulates tissue repair and stem cell maintenance.
Research environment: You will join two friendly, collaborative labs embedded in the Randall Centre for Cell and Molecular Biophysics and the Centre for Craniofacial Development at King’s College London. We are part of the UK Cell Motility Club, which I am organising. The KCL Nikon Imaging Centre provides state-of-the-art microscopy facilities, and we collaborate with the European Xenopus Resource Centre in Portsmouth for developmental studies.
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 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. 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. Law, A.-L., Jalal, S., Pallett, T., et al., 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; DOI: 10.1038/s41467-021-25916-6.
3. Dobson, L., Barrell, W.B., Seraj, Z., et al., 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) DOI: 10.1016/j.celrep.2023.113030. *Co-senior authors
4. Vehlow, A., Soong, D., Vizcay-Barrena, G., et al., and Krause, M. (2013) Endophilin, Lamellipodin, and Mena Cooperate to Regulate F-actin-dependent Endocytosis of the EGF-receptor. EMBO J. 32, 2722-2734.
5. 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.
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