Leveraging mechanobiology for the dissection of stem-like properties and therapeutic resistance potential in glioblastoma cells

About the Project

Project:

Classical understanding of cancer is that genetic factors, such as mutations, cause the disease, among others by changing consequentially biochemical signalling pathways and eventually cell behaviour, especially cell growth. In recent years, however, it becomes increasingly evident that genetics alone cannot explain the complexity of many cancers and that also the mechanobiology of the cancer cell and its surrounding microenvionment, in particular the extracellular matrix (ECM), plays a key role in cancer, including the primary brain cancer glioblastoma (GB). Normally, the dialogue between the cell and the ECM keeps the cells in balance and tells it, e.g., whether to divide or specialise in their function. In cancer, this dialogue is out of balance, leading to erroneous cell behaviour.

The mechanobiological aspect therein, lies in the fact that this dialogue is not only defined by biochemical factors (e.g., growth factors), but also by the mechanical/structural ECM properties and the forces that the cell generates to sense these properties, which, in turn, determine the mechanical properties of the cell themselves and their function. In cancer, the mechanics and structure of the ECM, particularly also its sugary component called glycocalyx, and the cells is altered. Recent indications suggest that these alterations contribute decisively to the capability of some glioblastoma cells to escape therapeutic treatments, leading to the cancer returning. It remains a major challenge to understand the underlying intricate force-based and integrin adhesion complex (IAC)-mediated events in the cancer cell/microenvironment interface, called mechanosensing/transduction, that convert mechanobiological cues into cellular responses. This holds even more true for the attempt to leverage them as targets for novel therapeutic approaches.

The PhD project aims at gaining insight into the mechanobiology of the glioblastoma cancer cell dialogue with the ECM (and the related forces), which might allow to identify new targets for treatments that can address specifically glioblastoma cells that escaped conventional treatments (chemo/radiotherapy).

Mechanobiologically-relevant GB ECM features will be analysed and mimicked in biomaterials engineered with E-beam lithography and electrospinning (manipulating mechanotransduction-affecting parameters, e.g., the nanotopography). Patient-derived GB cells will be challenged with these substrates, applying GB-related therapeutic and glycocalyx-targeted treatments. A multi-technique strategy will monitor the impact on mechanotransduction, focussing on the IAC-mediated interface, and GB cell behaviour (e.g., therapeutic resistance). The analyses will comprise advanced bioimaging (AFM, Brillouin microscopy and deformability cytometry) and omics approaches, to 1) detect changes along the mechanotransductive sequence (e.g., composition and force loading of IAC and cytoskeleton) in dependency of the microenvironment and treatments, and 2) to dissect mechanotransduction-related (druggable) key regulators with potential to mitigate GB therapeutic resistance.

Environment:

The PhD student will be embedded in the (Extra)Cellular Mechanobiology in Health and Disease group at the Department of Biomedical Engineering of the University of Strathclyde, led by Dr Carsten Schulte.

The research project brings together an extensive interdisciplinary network, involving researchers from different University of Strathclyde institutions, the Centre for the Cellular Microenvironment (CeMi, where part of the works will take place), and the Universities of Glasgow, Edinburgh and Milan (Italy), integrating expertise from cell (mechano)biology, cancer biology, bioengineering, bioinformatics, and pharmacology.

Deadline:

The deadline to apply for this project is on the 14th of June 2026. Please send a CV and a motivation letter to: carsten.schulte@strath.ac.uk

Funding Notes

This PhD studentship will be embedded in a broader project funded by a Springboard award of the Academy of Medical Sciences held by Dr Carsten Schulte.

Funding has been secured for Home Studentship. To be treated as a home student, candidates must meet one of these criteria:

• be a UK national (meeting residency requirements)
• have settled status
• have pre-settled status (meeting residency requirements)
• have indefinite leave to remain or enter.