Adult stem cells are found in most tissues, and the interaction between stem cells and their niche tightly controls their self-renewal and differentiation state. Furthermore, environmental factors can ‘activate’ stem cells leading to acquisition of a migratory phenotype, homing to specific sites and differentiation to mediate tissue maintenance and repair. The stem cell microenvironment consists of a myriad of physical and biochemical cues, and these are decoded by stem cells to produce the appropriate response. How these mechanical and chemical factors that control stem cells are integrated to control stem cell behaviour, however, is not known.
We will use mesenchymal stem cells, which migrate and differentiate in a stereotypical manner in response to specific soluble factors, substrate mechanics and cytoskeletal tension, to understand signal integration. Combining cell biology approaches and state-of-the art microscopy (super resolution, FRET biosensors (Paul et al., 2015)) with mathematical modelling (Hetmanski et al., 2016, 2019, 2021) will allow us to understand signalling networks that govern division and migratory outcomes. We will further experimentally manipulate substrate rigidity, cell shape (using micropatterning) and the cytoskeleton to reveal their impact on intracellular signalling and inform mathematical models. This interdisciplinary approach will provide insight into stem cell behaviour and how it can be manipulated for application in tissue engineering.
1. Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject.
2. For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the PhD title.
3. For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit www.internationalphd.manchester.ac.uk