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.
Biddle, A., Gammon, L., Liang, X., Costea, D. E., and Mackenzie, I. C. (2016). Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma. EBioMedicine 4, 138-145.
Biddle, A., Liang, X., Gammon, L., Fazil, B., Harper, L. J., Emich, H., Costea, D. E., and Mackenzie, I. C. (2011). Cancer stem cells in squamous cell carcinoma switch between two distinct phenotypes that are preferentially migratory or proliferative. Cancer Res 71, 5317-5326.
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. (2015). TGF-beta-Induced Transcription Sustains Amoeboid Melanoma Migration and Dissemination. Curr Biol 25, 2899-2914.
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. (2010). Mapping the first stages of mesoderm commitment during differentiation of human embryonic stem cells. Proc Natl Acad Sci U S A 107, 13742-13747.
Hannezo, E., Scheele, C., Moad, M., Drogo, N., Heer, R., Sampogna, R. V., van Rheenen, J., and Simons, B. D. (2017). A Unifying Theory of Branching Morphogenesis. Cell 171, 242-255 e227.
Katz, E., Dubois-Marshall, S., Sims, A. H., Gautier, P., Caldwell, H., Meehan, R. R., and Harrison, D. J. (2011). An in vitro model that recapitulates the epithelial to mesenchymal transition (EMT) in human breast cancer. PloS one 6, e17083.
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. (2012). ECM microenvironment regulates collective migration and local dissemination in normal and malignant mammary epithelium. Proc Natl Acad Sci U S A 109, E2595-2604.
Nieto, M. A., Huang, R. Y., Jackson, R. A., and Thiery, J. P. (2016). Emt: 2016. Cell 166, 21-45.
O’Brien-Ball, C., and Biddle, A. (2017). Reprogramming to developmental plasticity in cancer stem cells. Dev Biol 430, 266-274.
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. (2014). Diverse matrix metalloproteinase functions regulate cancer amoeboid migration. Nature communications 5, 4255.
Scheele, C. L., Hannezo, E., Muraro, M. J., Zomer, A., Langedijk, N. S., van Oudenaarden, A., Simons, B. D., and van Rheenen, J. (2017). Identity and dynamics of mammary stem cells during branching morphogenesis. Nature 542, 313-317.