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3D bio-printing human pluripotent stem cell-derived skeletal muscle constructs for disease modelling and drug discovery


Blizard Institute

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Dr Y Y Lin , Dr J Connelly No more applications being accepted Funded PhD Project (European/UK Students Only)

About the Project

Applications are invited from highly motivated graduates with a BSc (First or Upper Second) or MSc (Distinction or Merit) from disciplines related to biomedical engineering, stem cell biology and regenerative medicine. Previous research experience would be an advantage. This is an exciting project funded by the NC3Rs and will commence on 1st October 2020. The successful candidate will be jointly supervised by Dr Yung-Yao Lin and Dr John Connelly at the Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London.

Background:
Recent studies suggest that myogenic culture with three-dimensional (3D) structure mimicking the organisation of muscle bundles in vivo is important for myofibre maturation and function. To facilitate pre-clinical drug discovery and development for muscle-related diseases, it is critical to develop novel human-specific 3D in vitro models that recapitulate the highly aligned muscle structure in vivo. As standard 3D culture does not reflect the complexity of myofibre architecture in vivo, we will use 3D bio-printing technologies to bridge this gap. Bio-printing involves the layer-by-layer deposition of living cells within a biocompatible material (‘bioink’) in order to build up a 3D tissue-like structure. Key advantages of this approach include high spatial control of the printed structure, the ability to create multi-cellular or multi-material tissues, and excellent reproducibility and consistency. Human iPSC-derived myogenic progenitors in combination with 3D bio-printing technologies can provide human-specific in vitro platforms critically needed for elucidating disease mechanisms and facilitating drug discovery1,2. This multidisciplinary project will have a significant impact on developing novel human-specific pre-clinical models and replacing/reducing the use of mouse models in muscular dystrophy research.

Environment:
The Blizard Institute supports researchers with the state-of-the-art core facilities, including the CREATE Biofabrication Lab for 3D bio-printing, which has been established as a multi-disciplinary initiative to provide cutting edge facilities for the engineering of advanced tissue and disease models. QMUL is one of the UK’s leading research-focused higher education institutions and a member of the Russell Group of elite UK Universities. In the 2014 Research Excellence Framework (REF), QMUL was ranked 9th out of all UK multi-faculty institutions in overall research outputs, impact and environment. These PRES2015 outcomes follow comments from the REF2014 UoA1 panel, which noted that a particular strength of Barts and The London School of Medicine and Dentistry was its ‘effective and sustainable doctoral research training and evidence of a strong and integrated research student culture’.

Funding Notes

The studentship is funded by NC3Rs and open to applicants with with a BSc (First or Upper Second) or MSc (Distinction or Merit) in a relevant discipline. The studentship will include a stipend of £17,241, PhD fees (at home/EU levels) and £8000 consumables per annum and will be funded for 3 years.

Application Process
Your application must consist of a CV, contact details of two academic referees, and a personal statement (1,000 words maximum) describing your suitability for this project.

Informal enquiries are encouraged before the closing date and can be made to Dr Yung-Yao Lin ([Email Address Removed])

References

1. Paredes‐Redondo, A. & Lin, Y.-Y. Human induced pluripotent stem cells: challenges and opportunities in developing new therapies for muscular dystrophies. in eLS 1–10 (Wiley, 2019). doi:10.1002/9780470015902.a0028371

2. Kim, J. et al. A new patient-derived iPSC model for dystroglycanopathies validates a compound that increases glycosylation of α-dystroglycan. EMBO Rep. 20, e47967 (2019).

3. Find out more about the PhD studentship:
https://nc3rs.org.uk/3d-bio-printing-human-pluripotent-stem-cell-derived-skeletal-muscle-constructs-disease-modelling-and
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