ºÚÁÏÉç

Lead ºÚÁÏÉç Supervisor: Dr. Gemma Brierley

Co-Supervisors: Dr Matthew Gage & Prof. Caroline Wheeler-Jones

Department: Comparative Biomedical Sciences

Background, aims and objectives:

Insulin is a hormone that elicits both metabolic and mitogenic effects on cells. The growth promoting activities of insulin may be harmful in several settings, including during the compensatory hyperinsulinemia that occurs due to insulin resistance. Excessive insulin action is thought to underlie the link between insulin resistance and cardiovascular disease. At time of diagnosis a significant number of people living with type 2 diabetes present with advanced vascular disease, due to the years of insulin resistance that precede the development of the hyperglycaemia that results in diagnosis of diabetes. In addition, some clinical features of severe insulin resistance syndromes, such as soft tissue overgrowth, reflect the excessive growth-promoting activity of sustained high-levels of insulin. Understanding the determinants of insulin’s metabolic and mitogenic actions, and whether these can be clearly dissociated, is therefore a critical question.  

The Brierley lab is currently engineering antibodies that activate the INSR as a novel treatment for severe insulin resistance caused by genetic defects in the insulin receptor. Importantly, for what would be a life-long treatment, the antibodies preferentially activate metabolic signalling pathways downstream of the insulin receptor, without activating mitogenic pathways. These antibodies are therefore also an important research tool to understand the mechanisms that link insulin resistance, diabetes, and development of cardiovascular disease. This PhD project will build upon preliminary proteomics studies that have identified antibody-activated insulin receptors preferentially associate with two other cell surface receptors. The project will aim to define the nature of these receptor interactions, whether they are responsible for the signalling bias.  

The PhD candidate will be trained in a variety of laboratory techniques such as: tissue culture, molecular biology assays, gene silencing, gene and protein expression assays, and state-of-the-art confocal microscopy utilising genomic code expansion and ‘click’-chemistry to visualise the receptors. The ºÚÁÏÉç has world-leading research facilities, and the supervisors are experts in all the techniques and models the candidate will need to successfully complete the project. By undertaking this project, the candidate will have the opportunity to contribute to the understanding of the pathogenesis of atherosclerosis in people living with insulin resistance and diabetes.

References

1. Brierley GV, Siddle K, Semple RK. (2018) Evaluation of anti-insulin receptor antibodies as potential novel therapies for human insulin receptoropathy using cell culture models. Diabetologia. 61(7):1662-1675
2. Brierley GV, Webber H, Rasijeff E, Grocott S, Siddle K, Semple RK. (2020) Anti-insulin receptor antibodies improve hyperglycemia in a mouse model of human insulin receptoropathy. Diabetes. 69(11):2481-2489
3. Brierley GV, Semple RK. (2021) Insulin at 100 years – is rebalancing its action key to fighting obesity-related disease? Dis. Model. Mech. 14(11):dmm049340.

Requirements

Essential:

• Degree in science, or similar field
• Enthusiastic, curious and flexible approach
• A desire to undertake robust and rigorous research in line with best practices for research integrity
• Good level of English literacy, numeracy, and experience of using computers to enter and organise data.

Desirable:

• Higher research degree, such as MSc
• Previous research experience
• Knowledge of research methods and design
• Ability to critically analyse data/information
• Ability to communicate effectively and work well with others

This project does not involve the direct use of animals

Fees and Funding

This is a 3-year fully-funded studentship, funded by the ºÚÁÏÉç internal studentship award. This funding covers 'Home' rate tuition fees and a stipend. 

This PhD studentship is fully funded by the Royal Veterinary College, which covers home tuition fees and provides a tax-free stipend of approx. £21,000 per year. Additional grants and bursaries are also offered by the ºÚÁÏÉç, subject to availability. All laboratory consumables and running costs will be covered by the host supervisors.

The studentship will commence in October 2025 at the ºÚÁÏÉç's Camden campus.

This studentship is open to applicants eligible for "Home" fees. International applicants are welcome to apply but must be able to fund the difference between "Home" and "Overseas" tuition fees. 

EU/EEA and Swiss national students starting studies in the 2021/22 academic year or later academic years may no longer be eligible to pay the “home” rate of tuition fees nor claim any financial support for their studies dependent on your personal circumstances (including immigration status and residence history in the UK). To help determine whether you would be eligible for home fees please see the UKCISA's 'Who pays 'home' fees for higher education in England?' guide found .

If you are interested in applying for this PhD project, please follow the link below.  Please use your personal statement to demonstrate any previous skills or experience you have in using both qualitative and quantitative research methods.

How to Apply

For more information on the application process and English Language requirements see How to Apply.

Interviews are expected to take place in person at our Camden campus or remotely in May/June (date TBC) 

We welcome informal enquiries - these should be directed to Dr Gemma Brierley (Lead Supervisor): gbrierley@rvc.ac.uk

Deadline: 25/04/2025