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Mechanomedicine: Nanotechnology & pharmaceuticals to augment the cell response to exercise

Project Description

Research project: Mechanomedicines are an emerging field of research in which mechanotransduction pathways (through which cells sense exercise and their physical environment) are therapeutically targeted by pharmacological and nanotechnological methods.
Lack of exercise contributes to many disease processes, especially degenerative diseases of the musculoskeletal system such as osteoarthritis, osteoporosis and sarcopaenia (muscle wasting). Although these are often considered inevitable consequences of ageing, a desire to stay healthy throughout our whole lifespan is a powerful driver for research into the mechanisms that lead to frailty and interventions that can prevent it. To date, only exercise has been shown to have a significant effect on maintaining musculoskeletal function as we age.

Mechanomedicines generally work by altering the effective thresholds for mechanosensors, thereby changing the cell sensitivity to a given force. In a sense, mechanomedicines can be considered as ‘exercise in a bottle’ - amplifying the tissue response to lower levels of physical activity, and driving beneficial changes such as increased functional bone density and improved cartilage resilience.
Using tissue engineering technology (3D in vitro cell culture and bioreactors), we will investigate the effectiveness of a range of novel mechanomedicines to lower mechanotransduction thresholds, e.g. activity in the MAPK and Hippo pathways, stretch-activated ion channel activation.

Mechanomedicines we propose to investigate include ampipathic crenelators and plant-derived dietary lipids (which distort and pre-stress the cell membrane), functionalised and targeted nanowires (to change the mechanical properties of the primary cilium), pharmaceuticals acting on stretch-activated ion channels and biomaterials with instructive nanotopography.

For more details on the research project please contact the supervisors
Dr James Henstock Institute of Ageing and Chronic Disease
Dr Jude Curran, School of Engineering
Dr Richard Barret-Jolley Institute of Ageing and Chronic Disease

Fourth supervisor: Dr Steven Percival (5D Health Protection Group)

Please apply by sending CV and letter of application to Ms Diane Ashton

Training: The University of Liverpool is setting up a Doctoral Network in Technologies for Healthy Ageing to train the next generation of physical scientists and engineers to develop novel technologies and devices to address the challenges faced by older people and our clinical colleagues who work with them. It is structured around three healthy ageing challenges; prolonging independence, maintaining wellness and accelerating recovery.

All students will undertake a specific training programme in conjunction with their research project. A range of training modules have been designed to provide the student cohort with the high levels of scientific knowledge and engineering expertise needed for research and development of devices and technologies appropriate for the Healthy Ageing agenda. Through this approach our students will learn skills that will provide them with a unique advantage to develop technologies appropriate for this community and significantly enhance their employability in this emerging field. At the start of the programme students will have a masterclass session with a consultant in clinical geriatric medicine, a therapist and a social worker to introduce them to the challenges of the older person in the community through case studies. Each student will spend a week with a Consultant Geriatrician in clinics and community visits. This clinician will remain in contact with the student throughout their PhD in the role of a mentor to maintain the interface between their projects and the healthcare challenges. Innovative training sessions will ensure the training and research is grounded in real world challenges and have been constructed to provide Essential Transferable Skills and Subject Broadening Skills. The student will be a member of the Liverpool Doctoral College which provides further training opportunities over all three years of the PGR programme, and includes Inductions (general and safety), E-learning (e.g. Good Research Practice), seminars (presenting as well as attending), outreach opportunities and journal clubs.

Funding Notes

Studentships will be funded for 3.5 years covering the home fees and typical Research Council stipend.
Research Council Doctoral stipend levels and indicative fees for 2019
• National Minimum Doctoral Stipend for 2019/20 is £15,009
• Research Councils UK Indicative Fee Level for 2019/20 is £4,327

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