Computational modelling to identify novel anti-inflammatory interventions to preserve musculoskeletal function in old mice.

The aims of this project are:

1. To use computational approaches to identify epigenetic changes responsible for changes in cytokine production seen in musculoskeketal tissues with advancing age.

2. To use this computational modelling to predict novel potential drug target sites.

3. To examine the effect of such interventions on musculoskeletal tissue structure and function in vivo in mice.

Brief experimental design:
This work applies powerful computational modelling to identify potential druggable targets to maintain musculoskeletal function in C57Bl6 mice during ageing. The effects of a minimum of three interventions on musculoskeletal structure and function will be tested using integrated analyses of muscle, tendon, ligament, joint and cartilage structure and function as appropriate. The investigators will also explore the potential use of zebrafish as an alternative testing system.

Outcomes:
The potential identification of a novel single or combination of interventions that will preserve musculoskeletal tissue structure and function during ageing.

The student will receive detailed training in the powerful technique of computer modelling of biological pathways under the supervision of Drs Proctor and Shanley (Newcastle). The modelling will be additionally informed by Iwanejko and McArdle (Liverpool) to identify potential drugable targets. The student will also receive extensive training in experimental design and implementation of pre-clinical interventions in mouse ageing models. Specifically, the student will train in a number of aspects of structural and functional analyses of musculoskeletal tissues as well as cellular and molecular biological approaches to determine, for example, the effects of proposed interventions on inflammatory markers in musculoskeletal tissues. All of the appropriate techniques are established in the Newcastle and Liverpool laboratories. The student will be embedded into an active research environment and the supervisory team will provide considerable opportunities to discuss research progress with regular face-to-face and Skype meetings.