2026 Watkins Group: Genetic therapies for Inherited Heart Muscle Disease

About the Research

The Watkins group uses molecular genetic analysis of heart disease to define disease mechanisms and create genetic therapies. We work primarily on inherited heart muscle diseases (cardiomyopathies) which have both rare variant and common variant (polygenic) components. These are common and serious diseases, affecting around 1 in 250 of the population and are the main cause of sudden death and heart failure in young adults.

Having defined the genes and genetic mechanisms underlying cardiomyopathy, our main focus now is on exploiting novel approaches to genetic therapy (nucleic acid therapies and gene editing) to create disease modifying, even curative, therapies for these devastating diseases.

Prof Watkins leads an international program, CureHeart, that won the BHF’s global Big Beat Challenge competition in 2022, that aims to develop transformational advances in this area (https://www.bhf.org.uk/what-we-do/our-research/cure-heart). We are developing gene silencing approaches, with RNA therapies and base or prime editing, for one set of disorders, and gene upregulation approaches for another set.

Students who join this programme will be jointly supervised by Prof Watkins and one of three independent group leaders who each bring specialist expertise:

            Assoc Prof Chris Toepfer - modelling the effects of cardiomyopathy mutations in myofilament protein genes, and of genetic therapies, in iPSC-derived cardiomyocytes,  organoids and mouse models.

            Assoc Prof Anuj Goel – computational approaches to using human genetics to predict individuals at high risk of severe cardiomyopathy and hence suitable for early trials of genetic therapy and to understand the polygenic contribution to cardiomyopathy.

            Assoc Prof Elizabeth Ormondroyd – clinical genetic and social science approaches to evaluating patient perspectives and psychosocial and ethical issues in the deployment of genetic therapies for cardiomyopathy.

Training Opportunities

Depending on a student’s prior experience and current interests, projects in the group would provide training in computational and wet lab aspects of human genetic analysis, including WGS & GWAS, creation and analysis of human iPSC-derived cardiomyocyte and/or mouse models (both via genome-editing with CRISPR-cas9), bulk and single cell RNAseq, cardiac phenotyping of mouse models and human subjects, and exploration of gene silencing (by antisense approaches) and/or gene editing (including use of Base editors and Prime editors) as potentially curative strategies for genetic diseases.

Students are encouraged to attend the MRC Weatherall Institute of Molecular Medicine DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence, and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

As well as the specific training detailed above, students will have access to a wide range of seminars and training opportunities through the many research institutes and centres based in Oxford.

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.

Additional Supervisors

1. Christopher Toepfer

2. Anuj Goel 

3. Elizabeth Ormondroyd 

Publications