Improving vascular compliance during ageing: How microtubules regulate actomyosin force generation in vascular smooth muscle cells (WARRENU21DTP)

Maintaining vascular compliance, the ability of blood vessels to change shape in response to changes in blood pressure, is essential for healthy aging. The vascular wall of large arteries, i.e. the aorta, is comprised of elastic and non-elastic components, that respectively provide elasticity and tensile strength to the vascular wall. As we age, the elastic components become degraded. This results in increased vessel stiffness and reduced vascular compliance, a risk-factor for numerous age-related diseases.

However, preventing the degradation of these elastic components is difficult. The Warren Lab therefore focuses on targeting Vascular Smooth Muscle Cells (VSMCs), the principle cell type of the aortic wall. These mechanosensitive cells respond changes in aortic shape by producing actomyosin forces that contract the vessel back to its resting state. As the aortic wall stiffens due to aging, VSMCs respond by producing greater actomyosin forces. Thus, preventing the deformation of the vascular wall and reducing vascular compliance.

We have correlated increased VSMC actomyosin force generation with reduced microtubule acetylation, a marker of microtubule instability. This project seeks to understand: (1) the mechanistic relationship between microtubule acetylation and actomyosin force generation; (2) how microtubules regulate VSMCs ability to transfer actomyosin force through cell-matrix adhesion complexes; (3) whether targeted manipulation of microtubule stability can regulate VSMC actomyosin force production? This study has the potential to identify novel targets that will allow the pharmacological manipulation and restoration of aortic compliance during ageing.

The Warren Lab is a collaborative and enthusiastic research environment. This studentship will train you in a range of biomedical (hydrogel-based cell culture, qPCR, Western blotting) and imaging (confocal, traction force and atomic force microscopy) techniques. Those interested in cell, molecular, mechano- and vascular biology are encouraged to apply.

For more information on the supervisor for this project, please go here https://people.uea.ac.uk/derek_warren

This is a PhD programme.

The start date is 1st October 2021.

The mode of study is full time.

The studentship length is 4 years.


About NRP DTP:

The Norwich Research Park Biosciences Doctoral Training Partnership (NRPDTP) is open to UK and international candidates for entry October 2021 and offers postgraduates the opportunity to undertake a 4-year PhD research project whilst enhancing professional development and research skills through a comprehensive training programme. You will join a vibrant community of world-leading researchers. All NRPDTP students undertake a three-month professional internship placement (PIPS) during their study. The placement offers exciting and invaluable work experience designed to enhance professional development. Full support and advice will be provided by our Professional Internship team. Students with, or expecting to attain, at least an upper second class honours degree, or equivalent, are invited to apply.

This project has been shortlisted for funding by the NRPDTP programme. Shortlisted applicants will be interviewed on Thursday 7th January, Friday 8th January and Monday 11th January 2021.

Visit our website for further information on eligibility and how to apply: https://biodtp.norwichresearchpark.ac.uk/

Our partners value diverse and inclusive work environments that are positive and supportive. Students are selected for admission without regard to gender, marital or civil partnership status, disability, race, nationality, ethnic origin, religion or belief, sexual orientation, age or social background.