In situ deconvolution of Interferon receptor de-ubiquitination by BRISC-SHMT2 to normalise aberrant signalling in autoimmune diseases

Applications are now invited for one scholarship, commencing in October 2026. Interviews will be held May 2026.

<p>Type I interferons are critical cytokines that orchestrate innate and adaptive immune responses against viral infections and malignancies. The cellular response to interferons is tightly regulated by the availability and turnover of interferon receptors, particularly IFNAR1 and IFNAR2. Dysregulated interferon signalling is a crucial pathogenic component of autoimmune diseases from Rheumatoid Arthritis to Connective Tissue Diseases such as Lupus, Systemic Sclerosis, Sjogren or Myositis. Current therapeutics blocking IFN signalling are effective but increase rate of viral infection and malignancies.</p> <p>Given the central role of Interferon signalling, the therapeutic frontier in autoimmune diseases is centred on the development of interventions that re-establish a healthy immune system rather than neutering its function.</p> <p>The BRISC deubiquitinating complex cleaves K63-linked polyubiquitin chains and, when associated with the metabolic enzyme SHMT2, regulates IFNAR1 ubiquitination to control interferon receptor surface levels and downstream signalling. Loss of BRISC function enhances IFNAR1 ubiquitination and attenuates interferon responses — making BRISC–IFNAR modulation an attractive strategy to dampen aberrant IFN signalling through a natural cellular mechanism rather than direct pathway blockade.</p> <p>This project combines cell biology, quantitative proteomics, and protein engineering to dissect interferon receptor biology at unprecedented resolution. Single-molecule biophysics via the Luminosa platform will resolve IFNAR dynamics directly in cells, while de novo-designed mini-proteins will serve as precision tools for modulating receptor ubiquitination. Together, these approaches will underpin a new class of pro-homeostatic therapeutics — aimed at normalising aberrant type I IFN signalling rather than suppressing it — with direct relevance to autoimmune disease.</p> <p>We seek to create a new generation of scientists who think differently, are passionate about doing research and will go on to transform our understanding of important biomedical problems. This University of Leeds ad hoc studentship associated with the Cheney Accelerator is addressing a frontier need in prevention of autoimmune diseases by bringing world class researchers from the <a href="https://leedsbrc.nihr.ac.uk/">Leeds Biomedical Research Centre</a> (Prof Francesco Del Galdo) and the <a href="https://astbury.leeds.ac.uk/">Astbury Centre for Structural Molecular Biology</a> (Prof Elton Zeqiraj). The Cheney Biomedical Accelerator for discovery and translation provides a vibrant, interdisciplinary environment, that extends from the physical sciences to clinical medicine. We build on an outstanding positive research culture, where you can develop your skills and flourish.</p> <p>In your first six months, you will build the biomedical and methodological foundations of the project through introductory training in microscopy and structural biology methods, giving you the opportunity to explore the science in depth and shape the aims around your interests. You will then focus on your PhD project for the remaining 3.5 years, supported by bespoke training in skills and resilience, public engagement, entrepreneurship, translation, and more.</p> <h5>Skills Expected to Gain by the End of the Studentship</h5> <ul> <li>Single-molecule biophysics using the Luminosa platform to resolve receptor dynamics in live cells</li> <li>Quantitative proteomics and mass spectrometry for pull-down experiments and protein interaction studies</li> <li>De novo protein engineering to design and deploy mini-proteins as tools for modulating receptor ubiquitination</li> <li>Advanced microscopy methods for imaging interferon receptor biology at high resolution </li> </ul> <h5>Highlights of the programme</h5> <ul> <li>Support from a dedicated programme co-ordinator</li> <li>A mentorship scheme where we help you to find an experienced mentor outside of your supervision team</li> <li>Access to truly world class research facilities for in situ and structural biology</li> <li>Maximised time for the main PhD project</li> <li>Support for career development and travel</li> <li>Opportunities to publish your research and a review article</li> <li>Extensive relevant taught and real-life training experiences</li> <li>Wide multidisciplinary supervisor pool (including clinician-scientists)</li> <li>Financial support</li> </ul>

<p>To apply for this scholarship opportunity applicants should complete an <a href="https://www.leeds.ac.uk/research-applying/doc/applying-research-degrees">online application form</a> and attach the following documentation to support their application.</p> <ul> <li>a full academic CV </li> <li>degree certificate and transcripts of marks </li> <li>Evidence that you meet the University's minimum English language requirements (if applicable)</li> </ul> <p>To help us identify that you are applying for this scholarship project please ensure you provide the following information on your application form;</p> <ul> <li>Select PhD in Medicine as your programme of study </li> <li>Give the full project title and name the supervisors listed in this advert </li> <li>For source of funding please state you are applying for a University of Leeds Cheney Accelerator Scholarship </li> </ul> <p>If English is not your first language, you must provide evidence that you meet the University's minimum English language requirements (below).</p> <p><em>As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Across all Faculties we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+ and people with disabilities. Applicants will always be selected based on merit and ability.</em></p>

Applicants to this scholarship in the School of Medicine should normally have an Undergraduate degree of 2:1 or above (or international equivalent) in a relevant subject area. A Master’s degree is desirable, but not essential. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Admissions Team prior to making an application.

The minimum English language entry requirement for postgraduate research study in the School of Medicine is an IELTS of 6.5 overall with at least 6.0 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid.

<p>We are offering 1 full-time PhD scholarship in the School of Medicine for one UK candidate, covering a maintenance grant matching UKRI maintenance stipend (£21,805 for 2026/27) and UK tuition fees for 4 years. The award will be made for one year in the first instance and renewable for a further period of up to 3 years, subject to satisfactory progress.</p> <p>Other Conditions:</p> <ul> <li>Applicants must not have already been awarded or be currently studying for a doctoral degree</li> <li>Awards must be taken up by 1^st October 2026</li> <li>Applicants must live within a reasonable distance of the University of Leeds whilst in receipt of this scholarship</li> </ul>

<p>For further information about the admissions process, please contact the FMH PGR Admissions team: <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p>