Aberdeen University Featured PhD Programmes
Aberdeen University Featured PhD Programmes
Engineering and Physical Sciences Research Council Featured PhD Programmes
Birkbeck, University of London Featured PhD Programmes
Birkbeck, University of London Featured PhD Programmes

Engineering the skeletal muscle stem cell niche using microporous tissue engineering constructs

  • Full or part time
  • Application Deadline
    Wednesday, January 23, 2019
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Background: Satellite cells are skeletal muscle stem cells that reside in a specific micro-environment called the niche and are responsible for muscle repair upon injury or diseases. The long-term regenerative capacity of satellite cells depends on the balance between cell differentiation and self-renewal; disruption of this balance underpins muscle aging, disease progression in muscular dystrophies and cancer, and loss of stemness upon isolation from muscles. This has preempted the use of satellite cells in cellular therapy, an issue that may be addressed by using biomaterials. The Borycki team reported recently an important role for the extra-cellular matrix proteins Laminins in the maintenance of satellite cell stemness. In parallel, the Claeyssens team has developed a novel technology to generate porous biodegradable devices made of polymers micro-structured into microwells that can mimic a stem cell niche, and showed that such devices promoted neural stem cell growth. This project plans to harness our knowledge of the natural satellite cell niche to engineer new biomaterials to grow and maintain satellite cells for cellular therapies.
Objectives: This project has two main objectives, which consist in 1) designing and testing biomaterials to support satellite cells, and 2) investigating growth, differentiation and self-renewal of satellite cells on these biomaterials.
Novelty and timeliness: This project combines a unique expertise in Sheffield in the production of highly porous biodegradable materials (e.g. polycaprolactone or polyglycerol sebacate) via emulsion templating (under patent consideration P243781GB) and further shaping by UV stereolithography, and in the culture and study of skeletal muscle stem cells in association with their myofibre. Recent progress in these two areas of research makes this proposal particularly timely.
Experimental Approach: Isolation of satellite cells, manufacturing of 3D biomaterials coated or not with distinct Laminins, analysis of cell behavior using advanced imaging and molecular techniques.
Bio-engineering holds the promise of facilitating cellular therapy for regenerative medicine. However, an in-depth understanding of cell behavior on biomaterials must be generated before translating this technology to the bedside. This project will use world-class research to gather important information on the interactions between satellite cells and biomaterials, and on the cellular and molecular properties of satellite cells grown on scaffolds using cutting-edge imaging and molecular techniques.

Science Graduate School
As a PhD student in one of the science departments at the University of Sheffield, you’ll be part of the Science Graduate School. You’ll get access to training opportunities designed to support your career development by helping you gain professional skills that are essential in all areas of science. You’ll be able to learn how to recognise good research and research behaviour, improve your communication abilities and experience the breadth of technologies that are used in academia, industry and many related careers. Visit http://www.sheffield.ac.uk/sgs to learn more.

Funding Notes

Please note that we have a number of fee scholarships available, please get into contact with Dr. Kai Erdmann in case you would like to know more: View Website

Entry requirements
First class or upper second 2(i) in a relevant subject. To formally apply for a PhD, you must complete the University's application form using the following link: View Website

*All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information*.

References

Rayagiri SS, Ranaldi D, Mohamad Azhar I, Raven A, Lefebvre O, Zammit P, and Borycki AG. (2018) Laminin-111 deposition in the satellite cell niche mediates satellite cell self-renewal during skeletal muscle regeneration. Nature Communications 9:1075.
Sherborne C, Owen R, Reilly GC, Claeyssens F (2018). Light-based additive manufacturing of PolyHIPEs: Controlling the surface porosity for 3D cell culture applications. Mat. & Designs 156: 494-503

How good is research at University of Sheffield in Biological Sciences?

FTE Category A staff submitted: 44.90

Research output data provided by the Research Excellence Framework (REF)

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