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(BBSRC NWD) Fibrillin-1: a master regulator of skeletal muscle function?

Funding
Funded
Study mode
Full-time
Apply by
Start date
Subject area
Biological and Biomedical Sciences
How to apply
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Overview

The microvascular bed is one of the most important tissues in the human body. It is involved in the supply of oxygen and nutrients, the removal of waste products, and delivery of cells crucial to tissue maintenance and repair (Kissane and Egginton, 2019). Impaired microvascular supply in skeletal muscle leads to inadequate tissue oxygenation and a reduction in production and delivery of key molecules.

About this opportunity

Impaired microvascular supply leads to severe exercise intolerance and locomotor dysfunction, and underpins many disease pathologies including diabetes, spinal cord injury, heart failure and ageing (Espino-Gonzalez, et al. 2021, Warren, et al. 2021). Changes in structural and functional kinetics of the microvasculature during ageing are currently poorly understood, and even less is known about the specific role the microvasculature plays in the mechanical function of skeletal muscle.

We have begun to unpick the dynamic signalling cascade of physiological angiogenesis (i.e. the process of expanding the capillary network in response to exercise) and have identified Fibrillin-1 (FBN1) as a potential regulator of targeted angiogenic remodelling. FBN1 has already been shown to underpin maladaptive soft and hard tissue remodelling and is known to be upregulated during ageing (Shorter et al. 2022). FBN1 appears to be a multifunctional regulator of skeletal muscle function, and understanding the process that governs the functionally meaningful expansion of the vascular bed is integral to effectively understand the fundamental biological mechanism of healthy ageing systems across the life course.

Therefore, the aim of this project is to uncover the importance of FBN1 on the microvascular and mechanical function of skeletal muscle.

Further reading

1. Espino‐Gonzalez, Ever, et al. “Abnormal skeletal muscle blood flow, contractile mechanics and fibre morphology in a rat model of obese‐HFpEF.” The Journal of physiology 599.3 (2021): 981-1001.
2. Kissane, Roger WP, and Stuart Egginton. “Exercise-mediated angiogenesis.” Current Opinion in Physiology 10 (2019): 193-201.
3. Shorter, E, et al. “Identifying novel osteoarthritis-associated genes in human cartilage using a systematic meta-analysis and a multi-source integrated network.” International Journal of Molecular Sciences 23.8 (2022): 4395.
4. Warren, Philippa M., et al. “Oxygen transport kinetics underpin rapid and robust diaphragm recovery following chronic spinal cord injury.” The Journal of physiology 599.4 (2021): 1199-1224.

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Who is this for?

Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.

International applicants

We are only able to offer a limited number of full studentships to applicants outside the UK. Therefore, full studentships will only be awarded to exceptional quality international candidates due to the competitive nature of this scheme.

International applicants must ensure they meet the academic eligibility criteria (including English language) before applying. Visit our English Language requirements page to find out more.

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Liverpool, and is at the heart of all of our activities. The full equality, diversity and inclusion statement can be found on our website.

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How to apply

  1. 1. Contact supervisors

    The student will be joining the lab of Primary Supervisor Dr Roger Kissane [https://www.liverpool.ac.uk/people/roger-kissane] whose research focuses on understanding the physiology of muscle function. The Second Supervisor Dr Blandine Poulet [https://www.liverpool.ac.uk/people/blandine-poulet] whose work seeks to understanding factors involved in the pathogenesis of osteoarthritis. Together, the student will be joining a vibrant research group within the department of Musculoskeletal and Ageing Sciences. They will be trained in a broad range of interdisciplinary research techniques, including but not limited to in vivo and ex vivo physiology techniques, tissue histology, and molecular biology.

  2. 2. Prepare your application documents

    Browse our BBSRC NWD in Bioscience projects and discover one you’re passionate about that matches your interests, ambitions and goals.

    Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

    How to Apply

    All applications should be submitted through the University of Manchester application portal.

    Apply directly via this link, and select BBSRC DTP PhD as the programme of study. You may apply for up to two projects from the programme via this scheme. To do so, submit a single online application listing both project titles and the names of both main supervisors in the relevant sections.

    Please ensure that your application includes all required supporting documents:

    • Curriculum Vitae (CV)
    • Supporting Statement
    • Academic Certificates and Transcripts

    Incomplete or late applications will not be considered.

    Applications should not be made through the University of Liverpool’s application portal.

    You must submit your application form along with the required supporting documents by the deadline date. You can select up to two projects on one single application, noting the title of each project from the advert and the supervisor name. This can include two projects from one institution or a project from each institution.

    Once you have completed your application, you’ll receive a confirmation email.

    Deadline: Sunday 7th December, midnight (UK time)

    Late or incomplete applications will not be considered.

    If you need help with this stage of the process, or have any queries regarding your eligibility (such as if you achieved unexpectedly low degree results due to extenuating circumstances), please contact the Liverpool BBSRC team for advice at 

  3. 3. Apply

    Finally, register and apply online. You'll receive an email acknowledgment once you've submitted your application. We'll be in touch with further details about what happens next.

    Once you have applied through the University of Manchester portal, and if you are successfully offered a studentship following a formal interview, you will be instructed to apply formally through the University of Liverpool. You must only do this once you have been instructed to do so.

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Funding your PhD

These studentships are available to UK and international applicants, and provide funding for tuition fees and stipend at the UKRI rate, subject to eligibility, for four years. This does not include any costs associated with relocation. This scheme is open to both UK and international applicants.

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Contact us

Have a question about this research opportunity or studying a PhD with us? Please get in touch with us, using the contact details below, and we’ll be happy to assist you.

Liverpool BBSRC team
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