Designing therapeutic approaches for a new group of neurodevelopmental conditions associated with V-ATPase dysfunction

About the Project

Variants in V-ATPase encoding genes are increasingly linked to neurodevelopmental conditions for which there is no treatment. This project will explore small molecules and RNA-based therapies to combat these devastating conditions.

This PhD project will address a major unmet need in rare neurological diseases: the recently identified group of V-ATPase disorders, which currently have no cure and limited diagnostic tools. These conditions can severely affect children and adults with early onset neurological conditions, yet the biological mechanisms remain poorly understood. This project uncover how genetic variants in V-ATPase subunits disrupt brain development, neuronal function to translate this knowledge into new therapeutic strategies.

The student will be provided with training in stem cell modelling, multi-omics technologies, advanced imaging and RNA therapy development, to develop personalised treatment candidates. The PhD student will work with patient-derived cells, human neuronal models, model organisms and computational approaches to identify disease mechanisms, develop functional assays, and evaluate RNA-based therapies tailored to individual mutations. Close collaboration with patient organisations will ensure that this research is informed by real-world patient needs; outreach will be one of the goals of this project.

The specific objectives of this project include:

• Increase the understanding of V-ATPase-related conditions through omics data integration from patient cells
• Optimise disease models
• Design and test RNA-based therapies to regulate mutant transcripts to ameliorate disease progression
• Determine patient needs for effective interventions in collaboration with patient organisations

This project will equip the PhD students with the skills needed to accelerate progress in precision medicine. The project contributes directly to key UN Sustainable Development Goals by improving health and reducing inequalities, providing high-quality education, and strengthening international partnerships to advance treatments for underserved rare disease communities.