Musculoskeletal tissues ageing: the role of miroRNAs and biological clocks (Liverpool)
As the ageing population increases, it is essential to determine the mechanisms involved in musculoskeletal tissue deterioration. Musculoskeletal tissues dysfunction is among the most common diseases affecting older people ultimately leading to frailty, falls and decreased quality of life. Circadian clock is a conserved molecular timing system that governs various aspects of our physiology and metabolism. microRNAs, novel regulators of gene expression, affect the functionality of most cell types and provide a high-throughput response mechanism to ageing. As dysregulation of microRNAs, including microRNAs regulating circadian rythms, has been demonstrated, and microRNAs can simultaneously regulate many signalling pathways related to specific physiological physiological process(es), we hypothesize that by correcting the expression of selected microRNAs during ageing, we can, at least partially, restore the function of the musculoskeletal tissues. The training will provide an excellent portfolio of cutting-edge research skills and will give the student an opportunity for personal development. The training will be in an area highly relevant to future careers. As our population is ageing, there is a great need for better predicting and treating ageing-related disorders. In fact, this study is very timely - the first clinical trial against ageing per se using metformin has been proposed. This project will use state-of-the-art molecular biology approaches, bioinformatic techniques, real-time bioluminescence imaging as well as in vitro and in vivo model systems to demonstrate circadian regulation of microRNA:target interactions in the musculoskeletal tissues, how they change during ageing and whether scheduled lifestyle interventions can improve these dysregulated interactions and restore musculoskeletal tissue function during ageing. This may lead to the design of novel interventions to improve musculoskeletal tissues function, reducing frailty in older people and improving their healthspan and well-being. This could eventually reduce pressure on the health care system.
For further information see the website: https://www.liverpool.ac.uk/ageing-and-chronic-disease/
Please submit a full CV and covering letter directly to [Email Address Removed]
This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£14,057 for 2015-16). The PhD will start in September 2016. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. There are 2 stages to the application process.
Tew SR, McDermott BT, Fentem RB, Peffers MJ, Clegg PD. (2014)Transcriptome-wide analysis of mRNA decay in normal and osteoarthritic human articular chondrocytes. Arth Rheum. Nov; 66(11):3052-61. doi: 10.1002/art.38849.