Regenerating insulin cells by using new designer biologics to fine-tune neural signals. MRC GW4 BioMed DTP PhD studentship for 2026/27 Entry, Department of Clinical and Biomedical Sciences Ref: 5653

Supervisors

Lead Supervisor:  Dr Yu Hsuan Carol Yang - University of Exeter - Department of Clinical and Biomedical Sciences 

Co-supervisors:

Dr Jonathan Phillips - University of Exeter - Department of Biosciences

The GW4 BioMed2 MRC DTP is offering up to 17 funded studentships across a range of biomedical disciplines, with a start date of October 2026.

These four-year studentships provide funding for fees and stipend at the rate set by the UK Research Councils, as well as other research training and support costs, and are available to UK and International students.

About the GW4 BioMed2 Doctoral Training Partnership

The partnership brings together the Universities of Bath, Bristol, Cardiff (lead) and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities, with opportunities to participate in interdisciplinary and 'team science'. The DTP already has over 90 studentships over 6 cohorts in its first phase, along with 80 students over 4 cohorts in its second phase.

The 122 projects available for application, are aligned to the following themes;

• Infection, Immunity, Antimicrobial Resistance and Repair

• Neuroscience and Mental Health

• Population Health Sciences

Applications open on 1 September 2025 and close at 5.00pm on 20th October 2025.

Please note that we may close the application process before the stated deadline if an unprecedented number of applications are received– check our website for details.

Studentships will be 4 years full time. Part time study may also be available.

Project Information

Research Theme:  Population Health Sciences

Summary:

A hallmark of type 1 diabetes is elevated blood glucose levels caused by autoimmune destruction of the insulin-producing beta-cells. The existence of remnant beta-cells in patients with type 1 diabetes suggests that we could harness these cells to reverse the disease. This treatment would require strategies to expand the residual beta-cell pool, improve beta-cell functionality, and cloak beta-cells from further autoimmune attack. In this project we will explore the impact of pancreas innervation on beta-cell regeneration and the underlying mechanisms by designing new biologics with generative AI tools and using them to fine-tune the kinetics of endogenous galanin neuropeptide signalling. 

Details:

The role of neurons in all aspects of pancreas biology remains underexplored. The peripheral nerves in the pancreas can affect pancreatic islet development, proliferation and hormone secretion, and modulate autoimmunity. In addition to the role of adrenergic and cholinergic signalling, galanin nerve fibres are also found in the pancreatic islets of several vertebrate species including zebrafish, rodents, dog, baboon, and human. We are focused on galanin signalling, given its role in regulating hormone release from different islet cell types (including insulin from beta-cells and glucagon from alpha-cells) and in modulating immune signalling. Tools for precisely controlling pancreatic nerves and monitoring the effects in islets of living animals are difficult to implement in mammalian models. Therefore, we turn to the miniature and translucent zebrafish model where studies are translatable to human disease given the high conservation of organs and physiology. 

Understanding how nerves regulate beta-cell regeneration is important when developing therapeutics targeting this network to replenish beta- cell mass in diabetes. Building on our preliminary data, we will address how galanin signalling regulates beta-cell regeneration and design new biologics that can harness endogenous galanin signalling to enhance beta-cell regeneration. We have established assays necessary for studying neural-pancreas interplay in live zebrafish (Yang group) and have expertise in computational drug design, protein engineering and biochemical measurements (Phillips group). This project will implement these tools to target galanin producing peripheral nerves to address the following two aims: 

Aim 1: Investigate how galanin signalling promotes regeneration of beta- cells. 

Our preliminary data show significant changes in beta-cell regeneration upon loss of galanin nerve input, suggesting that galanin signals impact beta-cell regeneration. However, the underlying mechanism remains unclear. For this aim, we will investigate the cellular mechanisms driving the perturbances in beta-cell regeneration in our galanin loss-of-function model. These studies will be supervised by Dr. Carol Yang.

Three sources of endogenous beta-cell regeneration are described in the literature (proliferation of pre-existing beta-cells, neogenesis from progenitors, and transdifferentiation from other pancreatic cells). While most studies have supported proliferation as the predominant mode of beta-cell regeneration, under extreme beta-cell loss, neogenesis and transdifferentiation could occur. The student will assess the source of new beta-cells with in vivo confocal imaging of various fluorescent reporters, including ins:FUCCI (for proliferation) and Tp1:VenusPest (for neogenesis). Lineage tracing with gcga:CreERT2; ubb:SWITCH will identify the contribution from alpha-cell transdifferentiation. 

Additionally, we will investigate whether the functional recovery of beta- cells depends on galanin signalling. Following beta-cell regeneration, the student will conduct calcium imaging to analyse beta-cell synchronicity as a measure of islet maturity and associate the findings to changes in glucose levels. 

Early recruitment of innate immune cells is important for regeneration. The student will analyse differences in neutrophil and macrophage recruitment during the process of beta-cell regeneration and assess differences upon loss of galanin signalling. Next, we will increase or deplete immune cell numbers to determine if galanin regulation of immune cell recruitment is critical for driving beta-cell regeneration. 

These studies will identify the cellular source of regenerated bet-cells and the address the role of neural-immune signalling in the process. Aim 2: Design allosteric modulators to fine-tune endogenous galanin signalling and increase beta-cell regeneration. 

Our recent findings revealed the remodelling of the islet galanin nerve network upon beta-cell loss in zebrafish and during beta-cell regeneration. Given galanin nerves persist in the islet, we will address if harnessing this endogenous galanin signalling could be beneficial for beta-cell regeneration. Under the supervision of Dr. Jonathan Phillips, the student will design biologics that bind to allosteric sites of galanin receptors to either increase or decrease the potency and/or efficacy of galanin signalling. The student will use generative AI protein-design tools (RFdiffusion, Protein MPNN, AlphaFold) to design the biologics and predict their impact on galanin signalling in silico. 

Next, the student will synthesise and test the biologics in vitro using a human beta-cell line, EndoC-βH1. The beta-cells will be treated with recombinant galanin and the synthesised biologics. Cyclic-AMP (cAMP) is a secondary messenger downstream of galanin receptor signalling. The student will establish a live imaging assay of a luciferase-based cAMP biosensor to monitor the kinetics of cAMP production and simultaneously track beta-cell proliferation. The student will assess how the top candidates impact beta-cell regeneration in zebrafish using skills they develop during the completion of aim 1. 

 The student will work closely with a cross-departmental interdisciplinary supervisory team at the University of Exeter. This project will provide opportunities for them to develop well-rounded skills: including molecular biology techniques, in vivo imaging, data analysis, structural biology, generative AI protein design, protein engineering, computational modelling, and written/oral communication. Once trained 

Funding

This studentship is funded through GW4BioMed2 MRC Doctoral Training Partnership. It consists of UK tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£20,780 p.a. for 2025/26, updated each year).

Additional research training and support funding of up to £5,000 per annum is also available.

Eligibility

Residency:

The GW4 BioMed2 MRC DTP studentships are available to UK and International applicants. Following Brexit, the UKRI now classifies EU students as international unless they have rights under the EU Settlement Scheme. The GW4 partners have agreed to cover the difference in costs between home and international tuition fees. This means that international candidates will not be expected to cover this cost and will be fully funded but need to be aware that they will be required to cover the cost of their student visa, healthcare surcharge and other costs of moving to the UK to do a PhD.  All studentships will be competitively awarded and there is a limit to the number of International students that we can accept into our programme (up to 30% cap across our partners per annum).

Academic criteria:

Applicants for a studentship must have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualification gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences.  Applicants with a lower second class will only be considered if they also have a Master’s degree. Please check the entry requirements of the home institution for each project of interest before completing an application. Academic qualifications are considered alongside significant relevant non-academic experience.

English requirements:

If English is not your first language you will need to meet the English language requirements for the University of Exeter by the start of the programme. Please refer to the details in the following web page for further information https://www.exeter.ac.uk/study/englishlanguagerequirements/

Please check the relevant English Language requirements of the university that will host the PhD project.  

Data Protection

If you are applying for a place on a collaborative programme of doctoral training provided by Cardiff University and other universities, research organisations and/or partners please be aware that your personal data will be used and disclosed for the purposes set out below.

Your personal data will always be processed in accordance with the General Data Protection Regulations of 2018. Cardiff University (“University”) will remain a data controller for the personal data it holds, and other universities, research organisations and/or partners (“HEIs”) may also become data controllers for the relevant personal data they receive as a result of their participation in the collaborative programme of doctoral training (“Programme”).

Further Information

For an overview of the MRC GW4 BioMed programme please see the website www.gw4biomed.ac.uk

Entry requirements

Academic Requirements

Applicants for a studentship must have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualification gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences. Applicants with a lower second class will only be considered if they also have a Master’s degree. Please check the entry requirements of the home institution for each project of interest before completing an application. Academic qualifications are considered alongside significant relevant non-academic experience.

English Language Requirements

If English is not your first language you will need to meet the English language requirements for the University of Exeter by the start of the programme. Please refer to the relevant university website for further information.  This will be at least 6.5 in IELTS or an acceptable equivalent.  Please refer to the English Language requirements web page for further information.

Please check the relevant English Language requirements of the university that will host the PhD project. 

How to apply

A list of all the projects and how to apply is available on the DTP’s website at gw4biomed.ac.uk.  You may apply for up to 2 projects and submit one application per candidate only.

Please complete an application to the GW4 BioMed2 MRC DTP for an ‘offer of funding’.  If successful, you will also need to make an application for an 'offer to study' to your chosen institution.

Please complete the online application form linked from our website by 5.00pm on Monday, 20th October 2025.  Please note that we may close the application process before the stated deadline if an unprecedented number of applications are received– check the DTP’s website for details and updates

If you are shortlisted for interview, you will be notified from Tuesday, 23rd December 2025.  Interviews will be held virtually on 27th and 28th January 2026.  

Further Information

For informal enquiries, please contact GW4BioMed@cardiff.ac.uk

For project related queries, please contact the respective supervisors listed on the project descriptions on our website.

Summary