Developing an in Vitro Tissue-Engineered Skeletal Muscle Model to Study Ageing and Associated Conditions

(I) Scientific Excellence
Skeletal muscle (and its interactions with tendon and bone) is important for maintaining body posture and locomotion by transmission of force and movement during muscular contraction. Reductions in muscle mass and function (sarcopenia) are a major clinical problem in old age, underpinning age-related morbidity, compromised balance, and increased risk of falls and fragility fractures. As a result of the rapid expansion in the elderly population, our healthcare system is under increasing pressure to cope with the burden of the significant increase of age-related morbidities. To better understand the mechanisms underlying this loss of muscle mass and function, and to address the health consequences of ageing, research has been conducted in cell and animal model systems. However, progress to off-set and develop cures for age-associated muscle wasting has been slow and marred by the interaction of many physiological systems in muscle wasting. A tissue-engineered muscle system may overcome some of these confounding factors.

(II) Research aims and/or research hypothesis, set within national/international context
The aim of this project is to develop a physiologically relevant cell model of skeletal muscle to evaluate responses to specific age-associated changes, such as increases in inflammatory cytokines and damaging reactive species adduction. This cell model will also facilitate drug discovery and enhance our understanding of nutritional supplements and exercise.

(III) Methodology, Research Design and Planning, novelty, ambition and Innovations
Myoblasts from humans will be collected from young and old donors and characterised for the presence of myogenic and ageing markers using molecular techniques (e.g., NanoString and Western blotting) and mitochondrial function using the Seahorse analyser. To assess the effects of nutrients key to musculoskeletal development and health on young and aged myoblasts, initially, myoblasts will be cultured 2D in a mechanically active environment (provided by a cell culture bioreactor) and exposed to nutrients key to musculoskeletal development and health. Follow on work will include the development of 3D tissue engineered muscle to replicate the structure and function of native muscle, and to model the ageing phenotype and associated conditions, and assess effects on regenerative capacity.

(IV) Alignment to NTU institutional strategic research priorities
The project fits within the Health and Wellbeing Theme given that age associated deterioration of the musculoskeletal system has severe health consequences. The development and exploitation of a physiologically relevant model of skeletal muscle also directly relates to the Medical Technologies and Advanced Materials Theme.

(V) Fit within the remit of the DTA, highlighting interdisciplinary aspects of the project
The current project fits directly under the remit of the DTA Applied Biosciences for Health, and more specifically under the focus of Healthy Ageing. The project involves interdisciplinary collaborations between sport and exercise scientists, human physiologists, cell biologists, and molecular biologists, providing an ideal platform to underpin the success of the project.

Applications

Applicants must apply using the online form on the University Alliance website at https://unialliance.ac.uk/dta/cofund/how-to-apply/. Full details of the programme, eligibility details and a list of available research projects can be seen at https://unialliance.ac.uk/dta/cofund/

The final deadline for application is Monday 8 October 2018. There will be another opportunity to apply for DTA3 projects in the spring of 2019. The list of available projects is likely to change for the second intake.