Maintaining aortic compliance, the ability of the aorta to change shape in response to changes in blood pressure, is essential for healthy ageing. The aortic wall is comprised of elastic and non-elastic components. As we age, the elastic components become degraded, increasing the stiffness and reducing aortic compliance. This is a major 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 principal cell type of the aortic wall. These mechanosensitive cells regulate aortic compliance by generating actomyosin-driven contractile forces that restore the aorta back to its resting state. As the aortic wall stiffens during ageing, VSMCs respond by producing greater actomyosin-derived forces. Thus, preventing the deformation of the aortic wall and reducing compliance. However, the mechanisms which regulate VSMC force generation in rigid environments are unknown.
Recently we have shown that VSMCs grown on rigid surfaces display decreased microtubule stability. We hypothesise that microtubule disassembly activates a RhoA/GEF-H1 signalling pathway, which in turn promotes actin polymerisation and enhances actomyosin-derived force production. This project seeks to determine if: (1) microtubule destabilisation promotes enhanced actomyosin force production; (2) targeting RhoA/GEF-H1 is sufficient to alleviate enhanced actomyosin force generation; and (3) RhoA alters cell-matrix adhesion signalling pathways in response to matrix stiffness.
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 (immunofluorescence, confocal and traction-force microscopy) techniques. Those interested in cell, molecular, mechano-, and/or vascular biology are encouraged to apply/discuss the project in further detail.
The Norwich Research Park Biosciences Doctoral Training Partnership (NRPDTP) is open to the UK and international candidates for entry in October 2022 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 Tuesday 25th January, Wednesday 26th January and Thursday 27th January 2022.
You can visit The Norwich Research Park Biosciences Doctoral Training Partnership pages for further information on eligibility and the application process.
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.