Systems-Mechanobiology of Ageing and Diseases

About the Project

The interplay between lifestyle and genetics significantly shapes the trajectory of ageing, influencing the emergence of challenges like frailty and diseases such as cancer, cardiovascular conditions, and neurodegenerative disorders. Yet, the most universal and potent risk factor for nearly all these conditions is age itself. As age advances, the risks of these diseases—and overall mortality—rise exponentially. However, the biological mechanisms driving the ageing process and their causal links to frailty and disease remain only partially understood.

To date, research has primarily focused on the genetic, epigenetic, hormonal, and molecular hallmarks of ageing. While these are undeniably important, an intriguing and underexplored dimension is the mechanical changes that occur as we age. For example, cardiac and skeletal muscle efficiency declines, the extracellular matrix undergoes mechanical alterations such as increased stiffness and crosslinking, and cancer cells modify their adhesive and migratory properties to facilitate metastasis. Crucially, these mechanical changes are not merely by-products of ageing—they actively influence cell behaviour. Stiff, fibrotic matrices, for instance, have been shown to exacerbate chronic inflammation or promote the unchecked proliferation of cancer cells.

This project seeks to unravel these complex relationships by developing innovative mechano-chemical systems models of cell-cell and cell-matrix interactions. Through cutting-edge multi-omics approaches, we will identify the key mechano-chemical pathways altered during ageing. Our modelling efforts will shed light on the intricate crosstalk between mechanical and signalling processes, helping to identify the hallmarks of age-related mechanobiological change. These insights will enable us to generate hypotheses for interventions that could mitigate the adverse mechanical effects of ageing, potentially paving the way for novel therapeutic strategies.

This highly interdisciplinary project offers an exciting opportunity to work at the intersection of systems biology, biophysics, and computational modelling. Collaborating closely with experimental, clinical, and engineering experts, you will contribute to advancing our understanding of the mechanobiology of ageing and its role in disease development.

Funding Notes

A scholarship for home students may be available. It is awarded in competition with other projects so if you are interested in a scholarship please contact f.spill@bham.ac.uk as soon as possible.

Strong applicants with external funding will also be considered.