Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition in developed countries, with a global prevalence of 30%. The severe form of MASLD, MASH (metabolic dysfunction-associated steatohepatitis), is characterised by fat accumulation, inflammation and frequently fibrosis in the liver, and increases the risk of developing life-threatening liver cancer. In addition, 70% of individuals with type 2 diabetes (T2D) have MASLD, and thereby a 2.5-fold greater mortality risk. Despite this global epidemic, the first therapy for MASLD was only provisionally approved for human use in the USA in 2024, and new approaches are urgently needed.

Lipid accumulation in the liver is a primary driver of MASLD, and various therapies currently in clinical trials focus on reducing lipid accumulation for the treatment of advanced liver disease. Using a comprehensive genetic screen in liver cells, we identified thousands of novel regulators of lipid metabolism highly relevant for therapeutic targeting.

Based on this genetic screen, this PhD project will focus on the development of machine learning algorithms to predict and pinpoint the most important regulators of lipid metabolism in the liver, and their impact on systemic blood glucose control. Specifically, this PhD project will focus on the development of machine learning approaches to predict the ability of the proteins identified in the genetic screen to regulate lipid accumulation and glucose metabolism in the liver, components of the project that will be carried out at The University of Manchester. This will be accompanied by testing the metabolic impact of the top candidate(s) in cell and/or mouse models of metabolic disease, which will be carried out at The University of Melbourne. Together, this project will forecast the effects of novel candidates on MASLD and T2D progression and will allow for effective therapeutic validation.

Eligibility

Applicants should have, or expect to achieve, at least a 2.1 honours degree or a master’s (or international equivalent) in a relevant science or engineering related discipline.

Funding

This 3.5 year PhD is fully funded. The successful applicant will receive an annual tax free (depending on circumstance) set at the UKRI rate (£19,237 for 2024/25). Tuition fees will also be paid. This PhD is a dual-award between The University of Manchester and The University of Melbourne.

Before you apply

If you apply for the Manchester-based position, please get in touch with [email protected] for more information.

How to apply

Apply online through our website: https://uom.link/pgr-apply-2425

When applying, you’ll need to specify the full name of this project, the name of your supervisor, if you already having funding or if you wish to be considered for available funding through the university, details of your previous study, and names and contact details of two referees.

Your application will not be processed without all of the required documents submitted at the time of application, and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered.

After you have applied you will be asked to upload the following supporting documents:

• Final Transcript and certificates of all awarded university level qualifications
• Interim Transcript of any university level qualifications in progress
• CV
• Supporting statement: A one or two page statement outlining your motivation to pursue postgraduate research and why you want to undertake postgraduate research at Manchester, any relevant research or work experience, the key findings of your previous research experience, and techniques and skills you’ve developed. (This is mandatory for all applicants and the application will be put on hold without it).
• Contact details for two referees (please make sure that the contact email you provide is an official university/work email address as we may need to verify the reference)
• English Language certificate (if applicable)

If you have any questions about making an application, please contact our admissions team by emailing [email protected] .

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. We know that diversity strengthens our research community, leading to enhanced research creativity, productivity and quality, and societal and economic impact.

We actively encourage applicants from diverse career paths and backgrounds and from all sections of the community, regardless of age, disability, ethnicity, gender, gender expression, sexual orientation and transgender status.

We also support applications from those returning from a career break or other roles. We consider offering flexible study arrangements (including part-time: 50%, 60% or 80%, depending on the project/funder).

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