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MRC DiMeN Doctoral Training Partnership: Evaluation of adult stem cell differentiation in the trabecular meshwork of the eye as a regenerative medicine approach for Glaucoma using novel polymer 3D scaffolds


Project Description

Glaucoma is a leading cause of irreversible blindness in the world and is an optic neuropathy affecting the vision of older adults. There is an urgent need for new approaches to treat Glaucoma and a regenerative medicine approach offers promise. The TM is 3D sieve-like structure of collagen beams lined with TM cells. As the eye ages, the number of functional TM cells declines, and this is accelerated in Glaucoma. We have identified groups of cells with stem cell-like properties residing in the TM. Why these cells do not repopulate the TM structure as we age is unknown. This exciting collaborative project will investigate the ability of TM cells to differentiate, migrate and repopulate the TM beams in altered 3D architecture.
The aim of this project is to: i) assess stem/progenitor cell differentiation and repopulation on novel 3D polymer scaffolds coated with different extracellular matrix (ECM) components at varying degrees of stiffness before ii) functional testing in ex-vivo human glaucoma perfusion models. Investigation of the 3D scaffolds will be in collaboration with our industrial Case Partner, Spheritech. The novel polymer structures are based upon a patented cross-linked peptide, poly-epsilon-lysine (peK) which closely resembles the 3D structure of the TM in the eye. The project is therefore appropriate for graduates with a diverse STEM background inclusive of engineers with an interest in biology and biotechnology.

The project brings together a multi-disciplinary supervisory team with expertise in stem cell biology, tissue engineering, and cell physiology with an industrial CASE partner that specialises in the development and manufacture of innovative biomaterials for application in regenerative medicines. As such the student will be exposed a wide variety of techniques from training in TM stem cell biology (tissue culture, mRNA & protein assays, confocal & live cell imaging and in vitro & ex-vivo functional analysis) which will be carried out at the Institute of Ageing and Chronic Disease, University of Liverpool and additional training in specialised stem cell physiology will be provided at the Institute of Genetic Medicine, Newcastle University. The manufacture of advanced material training will be provided by secondment to Spheritech.

In addition to scientific presentations and collaborations, the student will regularly engage with the clinical teams and Glaucoma patient groups of St Pauls Eye Unit promoting awareness and understanding of the clinical impact and societal context of research. The student will also communicate this to lay audiences through our outreach projects and will therefore acquire a breadth of transferable skills relevant to the pursuit of careers in academia, industry and the wider economy.
https://www.liverpool.ac.uk/ageing-and-chronic-disease/staff/carl-sheridan/
https://www.liverpool.ac.uk/ageing-and-chronic-disease/staff/rachel-oldershaw/
https://www.ncl.ac.uk/igm/staff/profile/annettemeeson.html#background
https://spheritech.com/

Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme can be found on our website:
http://www.dimen.org.uk/

Funding Notes

iCASE Award: Industrial partnership project
Fully funded by the MRC for 3.5yrs, including a minimum of 3 months working within the industry partner. Enhanced stipend, tuition fees and budget for consumables, travel and subsistence.
Studentships commence: 1st October 2019.

To qualify, you must be a UK or EU citizen who has been resident in the UK/EU for 3 years prior to commencement. Applicants must have obtained, or be about to obtain, at least a 2.1 honours degree (or equivalent) in a relevant subject. All applications are scored blindly based on merit. Please read additional guidance here: View Website
Good luck!

References

Shaharuddin B, Osei-Bempong C, Ahmad S, Rooney P, Ali S, Oldershaw R, Meeson A (2016) Human limbal mesenchymal stem cells express ABCB5 and can grow on amniotic membrane. Regenerative Medicine 1:273-86.
Bakiah Shaharuddin, Sajjad Ahmad, Nani Md Latar, Simi Ali, Annette Meeson. A human corneal epithelial cell line model for limbal stem cell biology and limbal immunobiology. Stem cells translational medicine published online Oct 2016, doi: [10.5966/sctm.2016-0175] 2017 6(3):761-766
Yu WY, Grierson I, Sheridan C, Lo ACY, Wong DSH. Bovine Posterior Limbus: An Evaluation of an Alternative Source for Corneal Endothelial and Trabecular Meshwork Stem/Progenitor Cells. Stem cells and development 2015;24:624-639.

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