LICAMM Targeted degradation of cardiovascular ion channels using engineered protein reagents

Ion channels are essential regulators of cardiac electrical activity and represent major therapeutic targets for the treatment of cardiovascular disease. However, conventional drugs typically act by blocking or activating channel function and often suffer from limited selectivity and unwanted side effects.

<p>Targeted protein degradation (TPD) has recently emerged as a transformative therapeutic strategy that enables the selective removal of disease-associated proteins rather than modulating their activity. While progress with TPD of intracellular proteins has already led to an approved therapeutic, TPD approaches for membrane proteins are also emerging rapidly [1,2].</p> <p>In this project, you will explore innovative approaches to selectively remove cardiovascular ion channels from the cell surface. You will investigate the design of engineered bispecific affinity reagents capable of simultaneously engaging ion channels and endogenous cellular trafficking pathways, thereby promoting receptor internalisation and degradation.</p> <p>The project sits at the interface of fundamental ion channel biology and therapeutic development, addressing an emerging area of biomedical research with significant translational potential.</p> <p><strong>Example Research Objectives</strong><br /> •    Design and generation of engineered affinity reagents targeting cardiovascular ion channels.<br /> •    Evaluation of the effects of new protein degraders on ion channel expression and function.<br /> •    Investigation of the mechanisms underlying ion channel degradation.<br /> •    Exploration of the therapeutic potential of targeted ion channel degradation for cardiovascular disease.</p> <p><strong>Training Environment</strong><br /> You will join a multidisciplinary and internationally collaborative research environment with expertise in ion channel biology, protein engineering, pharmacology, and therapeutic development. You will receive comprehensive training in modern experimental approaches and have opportunities to engage with both academic and industrial collaborators working in emerging therapeutic modalities.</p> <h5>References</h5> <ol> <li><a href="https://pubs.rsc.org/bm/article/14/2/426/312250/Recent-progress-in-targeted-membrane-protein">https://pubs.rsc.org/bm/article/14/2/426/312250/Recent-progress-in-targeted-membrane-protein</a> </li> <li><a href="https://pubs.rsc.org/bm/article/14/2/426/312250/Recent-progress-in-targeted-membrane-protein">https://www.nature.com/articles/s41586-026-11088-0</a></li> </ol>

<p>Please note these are not standalone projects and applicants must apply to the PhD academy directly.</p> <p>Applications can be made at any time. You should complete an <a href="https://medicinehealth.leeds.ac.uk/faculty-graduate-school/doc/apply-2">online application form</a> and attach the following documentation to support your application. </p> <ul> <li>a full academic CV</li> <li>degree certificate and transcripts of marks (or marks so far if still studying)</li> <li>Evidence that you meet the programme’s minimum English language requirements (if applicable, see requirement below)</li> <li>Evidence of funding to support your studies</li> </ul> <p>To help us identify that you are applying for this project please ensure you provide the following information on your application form;</p> <ul> <li>Select PhD in Medicine, Health & Human Disease as your planned programme of study</li> <li>Give the full project title and name the supervisors listed in this advert</li> </ul> <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 research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree.

If English is not your first language, you must provide evidence that you meet the University's minimum English language requirements. The minimum English language entry requirement for postgraduate research study in the School of Medicine for 2027/28 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>This project is open to applicants who have the funding to support their own studies or who have a sponsor who will cover these costs.</p>

<p>For further information about the admissions process please contact the Faculty Admissions Team:<br /> e:<a href="mailto:hlspgradmissions@leeds.ac.uk">hlspgradmissions@leeds.ac.uk</a></p>