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The stiffness of extracellular fibres and metastasis


   Department of Oncology and Metabolism

  Dr A Gad  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

This role supports an active research program to assess the molecular mechanisms underlying adhesive, mechanical and motile defects of metastasising cells.

Cancer development is marked by a massive increase of fibres in the extracellular

microenvironment. In contrast to the normal microenvironment, the cancer microenvironment promotes the growth of cancer cells (1). In addition, cancer cell migration along extracellular fibres causes tumour-cell invasion and metastasis, the number one cause of human death in cancer. However, how the fibres in the cancer microenvironment control cancer remains to be fully clarified.

In order to determine how the stiffness of extracellular fibres controls cancer, we will use microengineered nanofibres of different elastic modulus (2), seed normal and metastasising human cells on soft and stiff fibres, and analysed the size, shape, cell-fibre adhesions and the cytoskeleton of the cells.

The project will use several in vitro and other models and assays to inform us about cell adhesion, deformation, mechanics and motility. Key tools for the study include advanced microscopy techniques, including Super-resolution microscopy, Live cell imaging and Atomic force microscopy.

Taken together with earlier observations of the cytoskeletal and adhesion changes

that accompany oncogenic transformation and metastasis in these cells (3), our preliminary data are in line with the hypothesis that the elastic modulus/stiffness of nanofibres in the extracellular microenvironment contributes to the transformation of normal cells to cancer cells, and to cell invasion.

You will work within an interdisciplinary research environment on site at the University of Sheffield, UK in a diverse learning environment that presents an outstanding opportunity to develop technical skills, specific knowledge and professional scientific communication. The project provides not only the chance for exposure to novel academic, scientific, and applied learning, but a rare opportunity to experience cutting edge therapeutic development that crosses an unusual intersection of Biochemistry, Tumour cell biology, Bioengineering and Biomechanics. Publication opportunities are expected.


References

1. Alkasalias T. et al…Pavlova T. and Gad A.K.B. Proc Natl Acad Sci U S A. 2017,114(8):E1413
2. Baker B.M., et al. Nat Mater. 2015 (12):1262
3. Rönnlund D., Gad A.K.B. et al. Cytometry A. 2013 Sep;83(9):855
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