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Using biomaterials to investigate how ageing affects the anti-inflammatory properties of MSCs and their EVs - Reference: MIBTP_Ross_Ageing


College of Life & Health Sciences

About the Project

Applications are invited for four year Postgraduate studentships, supported by the Midlands Integrative Biosciences Training Partnership (MIBTP) (URL: https://warwick.ac.uk/fac/cross_fac/mibtp/pgstudy/phd_opportunities/structural_biology/activation) and Biotechnology and Biological Sciences Research Council (BBSRC) (URL: https://bbsrc.ukri.org/). Up to 6 studentships are available.

The studentships are available to start in October 2021.


Background to the Studentship


MIBTP scholars join a programme of skills training in year 1. Applicants are required to select an area of study (URL: https://warwick.ac.uk/fac/cross_fac/mibtp/areas_of_research/), but may join the programme with or without selecting a preferred project. The skills training programme includes short rotation projects and students are able to choose a PhD project once they have experienced these differing research environments.
Potential PhD projects are provided to give applicants an idea of the breadth of research within MIBTP and specific research topics at Aston University. You can browse the other projects available here (URL: https://www.findaphd.com/phds/program/midlands-integrative-biosciences-training-partnership-mibtp-funded-phd-studentships/?i369p1045). Additional projects will become available during Year 1 and students can work with potential supervisors during their first year to develop a particular project.

Project Outline


Cell based therapies have become an increasingly effective clinical approach for complex inflammatory conditions, due to their ability to both suppress the local immune response as well as promoting tissue regeneration. Mesenchymal stromal cells (MSCs) are a key cell type used for this cell therapy; these multipotent tissue progenitors can be isolated from a donor or patient, expanded in the laboratory and infused back into patients to exert anti-inflammatory and regenerative effects [1,2]. MSCs use a number of strategies to modulate an inflammatory environment, including release of soluble factors, cross-talk using surface proteins as well as the release of extracellular vesicles (EVs). However, producing sufficient MSCs for therapy in the laboratory is challenging. MSCs spontaneously differentiate in culture over time, losing their naïve, immuno-modulatory abilities [3]. Therefore, the ability to grow large numbers of undifferentiated, naïve MSCs in the laboratory remains a key goal for research.

We have recently described a functional link between metabolism, cell adhesion and immuno-modulatory function in MSCs[4]. In this study, we reveal that altering an MSCs growth surface modulates their metabolism, resulting in the maintenance of their naïve phenotype and prolonging their capacity to direct immune cell function. This PhD project will expand on these initial findings. Specifically, investigating how culturing MSCs on polymer based biomaterial surfaces affects the anti-inflammatory potential of their EVs. EVs are an emerging anti-inflammatory cell product, and a more defined strategy for reliably producing immuno-modulatory EVs could greatly reduce the therapeutic demand for large scale MSC cultures. After optimising the culture of naïve MSCs on new polymer based growth system (through collaboration with the University of Glasgow), changes to MSC physiology, metabolism and phenotype will be evaluated. EVs will be collected and characterised; effects on immune cell function will inform about the therapeutic potential of these cell products.

A key component of this work will be to directly compare effects of these culture conditions on MSCs from young or old donors. MSCs from older donors are less potent compared to those from younger donors, and this can be an issue when considering cells for therapeutic use. You will evaluate how this new culture approach modulates the biology of old versus young MSCs and their EVs. A better understanding of how aged cells react to expansion in culture compared to younger donors is important in order to potentially restoring full functionality back to aged MSCs and their EVs products.

This exciting project will provide you with practical working experience of progenitor cell biology, biomaterials and EVs. You will apply these skills in the areas of immunology, ageing and inflammation research. Using this multidisciplinary approach, you will gain experience in several areas of cutting edge research allowing further development and exploration of this project as you make it your own.

Full project details can be found here (URL: https://jobs.aston.ac.uk/Vacancy.aspx?ref=R200315).

Person Specification


The successful applicant should have been awarded, or expect to achieve, a Masters degree in a relevant subject with a 60% or higher weighted average, and/or a First or Upper Second Class Honours degree (or an equivalent qualification from an overseas institution) in a relevant subject. Full entry requirements for Aston University can be found on our website (URL:https://www.aston.ac.uk/study/courses/phd-life-and-health-sciences).

Full entry requirements for MIBTP can be found on their website (URL: https://warwick.ac.uk/fac/cross_fac/mibtp/pgstudy/phd_opportunities/application/#Eligibility).

Contact information

For further information on the advertised project, contact Dr. Ewan Ross at

Submitting an application

Details of how to apply for the studentship can be found here (URL: https://jobs.aston.ac.uk/Vacancy.aspx?ref=R200315).

If you require further information about the application process contact the Postgraduate Admissions team


Funding Notes

The studentships include a fee bursary to cover the Home fees rate, plus a tax free stipend of at least £15,285 p.a (to rise in line with UKRI recommendation).

Overseas Applicants
Overseas applicants may apply for this studentship, and the home fees rate will be covered. UKRI funding will not cover the difference between UK tuition fees and international tuition fees; international tuition fee payers will be required to fund the fee difference themselves. MIBTP encourages international students with existing sources of funding (e.g. fellowships) to apply. The difference between home and international fees is £13,443 in 2020/21. Please confirm in your application how you will fund the fee difference.

References

[1] -Tissue regeneration: The crosstalk between mesenchymal stem cells and immune response. Qi et al., J Cellular Immunology 2018. https://doi.org/10.1016/j.cellimm.2017.11.010
[2] – Challenges in clinical development of mesenchymal stromal/stem cells. Mastrolla et al., Stem Cells Trans Med 2019. https://doi.org/10.1002/sctm.19-0044
[3] – Bone marrow-derived mesenchymal stem cells change phenotype following in vitro culture: implications for basic research and the clinic. Bara et al., Stem Cells 2014. https://doi.org/10.1002/stem.1649
[4] – Nanotopography reveals metabolites that maintain the immunosuppressive phenotype of mesenchymal stem cells. Ross et al., 2019. https://doi.org/10.1101/603332

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