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PhD Studentship (4 years) - Using biomaterials to investigate how ageing affects the anti-inflammatory properties of MSCs and their EVs

School of Biosciences

Location:  Aston University Main Campus
Basis:  Full Time
Closing Date:  23.59 hours GMT on Sunday 10 January 2021
Reference:  R200315
Release Date:  Tuesday 10 November 2020

Supervisor: Dr Ewan Ross

Associate Supervisors: Professor Andrew Devitt

Project Reference: MIBTP_Ross_Ageing

BBSRC Strategic Research Priority: Immunology, Stem Cells, Ageing

Applications are invited for four year Postgraduate studentships, supported by the Midlands Integrative Biosciences Training Partnership (MIBTP) and Biotechnology and Biological Sciences Research Council (BBSRC). Up to 6 studentships are available.

The studentships are available to start in October 2021. 

Financial Support

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."

Background to the Studentship

All MIBTP scholars will join a programme of skills training in year 1. Applicants are required to select an area of study (Sustainable Agriculture and Food, Understanding the Rules of Life, Renewable Resources and Clean Growth or Integrated Understanding of Health) but may join the programme with or without selecting a preferred project. Part of 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. 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, expanded in the laboratory and infused into patients to exert both anti-inflammatory and regenerative effects with out the harmful side effects of immunosuppressive drug treatments[1,2]. MSCs use a number of strategies to modulate an inflammatory environment, including release of soluble factors, cross-talk mediated by surface proteins as well as the release of extracellular vesicles (EVs). Immunomodulation by EVs is an exciting and novel mechanism by which the immune system may be modulated for therapeutic benefit. Importantly, it highlights that EVs, rather than the MSC alone, have therapeutic potential and this would greatly reduce the number of cells required for therapeutic efficacy.  

Producing sufficient MSCs for therapy in the laboratory is challenging. MSCs spontaneously differentiate in culture over time, losing their naïve, immuno-modulatory abilities, instead committing to differentiate to mature stromal lineages[3]. Therefore, the ability to grow large numbers of undifferentiated, naïve MSCs remains a key goal for research. We have recently described a new functional link between metabolism, cell adhesion and immuno-modulatory function in MSCs[4]. In this work, we reveal that altering an MSCs growth surface by using distinct biomaterials modulates their metabolism, resulting in the maintenance of their naïve phenotype and prolonging their capacity to direct immune cell function. This has provided a new reliable approach for the culture of naïve MSCs and this new study will look to use the potential of this system to explore how this affects EVs functionality.

This PhD will develop a new area of research, specifically investigating how maintaining MSCs in a naive state with biomaterials affects the anti-inflammatory potential of their EVs. You will optimise the culture of naïve MSCs on polymer based growth systems (through collaboration with the University of Glasgow). These allow delivery of both an adhesive and soluble factor signal to the MSCs, allowing “tuning” of the growth conditions. Changes to MSC physiology and phenotype will be assessed as well as immuno-suppressive function on T cell proliferation. Once optimal conditions have been established, EVs will be collected, characterised, phenotyped and their cargo contents examined using established techniques at Aston. Effects of MSCs derived EVs on macrophage biology as well as T cell function will inform about the therapeutic potential of these cell products.

Importantly, this approach will allow the evaluation on the effects of donor age on MSC expansion and EVs biology in culture. Older donors often have MSCs which are less potent compared to those from younger donors. As patients with chronic inflammatory conditions are often in the older population, a better understanding of how aged cells react to expansion in culture compared to younger donors may reveal new methods for restoring full functionality back to aged MSCs and their EVs products. Therefore, a key component of this work will be to directly compare the functional effects of new culture conditions on young versus old donor MSCs and EVs.

This exciting project will provide you with practical working experience of progenitor 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.

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

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.

Evidence of quantitative training is required. For example, AS or A level Maths, IB Standard or Higher Maths, or university level maths/statistics course. Full entry requirements for MIBTP can be found on their website.

Contact information

For further information on the advertised project, please contact Dr. Ewan Ross at e.ross1@aston.ac.uk

Submitting an application

In order to apply for the MIBTP PhD studentship you must:

  1. Check your eligibility. 
  2. Complete a PhD application form on the Aston University website. From the drop-down options select School of Life and Health Sciences; October; Full time; Postgraduate Research; “Research Biomedical Sciences October 2021 Entry (Full-time)”.
  3. Notify MIBTP of your application by completing the online notification form; ensuring that you upload a current CV to the form.
  4. Review the MIBTP Data Privacy Policy to understand how we process your personal data.


When completing the Aston University application form, you will need to ensure to include the following documents

  • Copies of your academic qualifications for your Bachelor degree, and Masters degree (if studied); this should include both certificates and transcripts, and must be translated in to English.
  • A personal statement*
  • A copy of your current CV
  • Two academic references
  • Proof of your English Language proficiency for non-Native English speakers, further details can be found on our website

*Please note that a project proposal is not required, however your Personal Statement should address your ability & knowledge of the research area.  Where applying for a specific project, please include the supervisor name, project title and project reference in your Personal Statement. 

If you require further information about the application process please contact the Postgraduate Admissions team at pgr_admisssions@aston.ac.uk 

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Further particulars and application forms are available in alternative formats on request i.e. large print, Braille, tape or CD Rom.

If you have any questions, please do not hesitate to contact HR via recruitment@aston.ac.uk


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