PhD Position – Zebrafish Models for CASK Related Disorders, University of Portsmouth

Variations in the CASK gene cause a rare disorder called microcephaly with pontine and cerebellar hypoplasia (MICPCH). Affected children have small heads, skull abnormalities, seizures, and severe intellectual and motor disabilities. Increased cell death has been reported in the brains of developing and postnatal CASK mutant mice, suggesting a potential role of apoptosis in MICPCH pathogenesis. Unfortunately, little is known about the function of CASK in brain development, making it difficult to design disease-modifying therapies for CASK-related disorders.

This project will use the zebrafish model system to uncover the mechanisms by which CASK regulates brain development and neuronal survival. The student will employ state-of-the-art CRISPR/Cas9 genome editing to generate novel zebrafish mutants for caska and caskb, the two zebrafish orthologues of CASK. These models will provide a unique opportunity to explore the impact of CASK loss on the developing brain, cranial neural crest, and glial cell function.

The project will combine advanced imaging and molecular approaches to investigate when and where neuronal apoptosis occurs in CASK mutants and whether glial cells, which play a central role in neurodegeneration, contribute to this process. By integrating genetic, cellular, and developmental analyses, the student will contribute to a deeper understanding of the cellular mechanisms underlying CASK-related disorders.

This PhD will provide comprehensive training in zebrafish genetics, neurodevelopmental biology, fluorescence imaging, and quantitative data analysis. The student will join a vibrant research environment at the University of Portsmouth, with opportunities for collaboration across groups specialising in neural repair, neuroinflammation, disease modelling, and multi-omics approaches.

Overall, this project offers the opportunity to develop advanced research skills while contributing to novel insights into a devastating neurodevelopmental disorder, with potential long-term implications for therapeutic strategies.

The PhD will be based in the Institute of Live Sciences and Health, University of Portsmouth, and will be supervised by Dr Jordi Cayuso and Professor Matt Guille.

Please use the link below for information and applications.

Funding Notes