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Cellular plasticity and heterogeneous modes of migration in development, health and disease

Cellular plasticity and heterogeneous modes of migration in development, health and disease

Quantitative analysis of biological phenomena is key to advancing our understanding of their mechanistic underpinnings. Currently, the modes by which epithelial cells migrate in tissue development, regeneration and disease are only partially understood, mostly in qualitative terms. In this project, the student will develop a quantitative method for the analysis of cell migration in 3D under these different tissue states. A visit to our collaborating lab (Hannezo) at IST Austria will enable the student to learn biophysical modelling techniques that they can apply to their quantitative data to elucidate general rules governing cell migration in development, health and disease.

Disciplines and Techniques
Project supervisor/s
Dr. Adrian Biddle
Adrian is interested in demonstrating that human cells in a dish can form an effective model for the development of drugs that target these cells.
Queen Mary University of London
Professor Victoria Sanz-Moreno
Victoria is interested in interested in how ROCK and the actomyosin cytoskeleton cross-talks with transcription factors, and how this communication influences metastatic behaviour in both cancer cells and the tumour microenvironment.
Queen Mary University of London
References
Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma.
Biddle, A., Gammon, L., Liang, X., Costea, D. E., and Mackenzie, I. C.
EBioMedicine 4, 138-145
2016
Cancer stem cells in squamous cell carcinoma switch between two distinct phenotypes that are preferentially migratory or proliferative.
Biddle, A., Liang, X., Gammon, L., Fazil, B., Harper, L. J., Emich, H., Costea, D. E., and Mackenzie, I. C.
Cancer Res 71, 5317-5326
2011
TGF-beta-Induced Transcription Sustains Amoeboid Melanoma Migration and Dissem.
Cantelli, G., Orgaz, J. L., Rodriguez-Hernandez, I., Karagiannis, P., Maiques, O., Matias-Guiu, X., Nestle, F. O., Marti, R. M., Karagiannis, S. N., and Sanz-Moreno, V.
Curr Biol 25, 2899-2914
2015
Mapping the first stages of mesoderm commitment during differentiation of human embryonic stem cells.
Evseenko, D., Zhu, Y., Schenke- Layland, K., Kuo, J., Latour, B., Ge, S., Scholes, J., Dravid, G., Li, X., MacLellan, W. R., and Crooks, G. M
Proc Natl Acad Sci U S A 107, 13742-13747.
2010
A Unifying Theory of Branching Morphogenesis
Hannezo, E., Scheele, C., Moad, M., Drogo, N., Heer, R., Sampogna, R. V., van Rheenen, J., and Simons, B. D.
Cell 171, 242-255 e227
2017
An in vitro model that recapitulates the epithelial to mesenchymal transition (EMT) in human breast cancer
Katz, E., Dubois-Marshall, S., Sims, A. H., Gautier, P., Caldwell, H., Meehan, R. R., and Harrison, D. J.
PloS one 6, e17083
2011
ECM microenvironment regulates collective migration and local dissemination in normal and malignant mammary epithelium
Nguyen-Ngoc, K. V., Cheung, K. J., Brenot, A., Shamir, E. R., Gray, R. S., Hines, W. C., Yaswen, P., Werb, Z., and Ewald, A. J
Proc Natl Acad Sci U S A 109, E2595-2604
2012
Emt: 2016
Nieto, M. A., Huang, R. Y., Jackson, R. A., and Thiery, J. P.
Cell 166, 21-45
2016
Reprogramming to developmental plasticity in cancer stem cells
O’Brien-Ball, C., and Biddle, A
Dev Biol 430, 266-274
2017
Diverse matrix metalloproteinase functions regulate cancer amoeboid migration
Orgaz, J. L., Pandya, P., Dalmeida, R., Karagiannis, P., Sanchez-Laorden, B., Viros, A., Albrengues, J., Nestle, F. O., Ridley, A. J., Gaggioli, C., et al.
Nature communications 5, 4255
2014
Identity and dynamics of mammary stem cells during branching morphogenesis
Scheele, C. L., Hannezo, E., Muraro, M. J., Zomer, A., Langedijk, N. S., van Oudenaarden, A., Simons, B. D., and van Rheenen, J.
Nature 542, 313-317
2017