DPhil projects available

Exome and whole genome sequencing to identify new genetic causes of skull malformations

How do cranial sutures work?

Funding

I hold a Project Grant with Action Medical Research, inlcuding funding for a postdoctoral researcher, Yan Zhou.

Growth of the skull vault is closely coordinated with expansion of the underlying brain and primarily occurs at cranial sutures. These are the narrow strips of fibrous mesenchyme separating the flat bones of the skull vault that contain a population of cells with the capacity to respond to changes in brain volume and control bone deposition at the sutural margins. Sutures fuse naturally after full brain size is achieved, but in approximately 1 in 2,250 children fusion occurs prematurely during fetal development or infancy. This is called craniosynostosis and it has potentially serious consequences for brain development and can lead to problems with vision, hearing, breathing and dentition. To understand why this happens our approach has been to identify underlying genetic causes. As well as providing invaluable information for patients and families, this has shed light on the embryological processes important for cranial suture development.

Ongoing research

Identification of non-coding mutations in craniosynostosis

There are many craniosynostosis patients, who have a potential genetic origin, but for whom we are not yet able to define a causative  variant. It may be that the causes lie in non-coding DNA - regions not routinely analysed in genetic diagnosis. To identify non-coding mutations our approach is to map regulatory elements (RE) that control the expression of genes involved in suture development and maintenance, and intersect this information with sequence data obtained from patients. This work is supported by Action Medical Research .

 Cranial suture development

We do not fully understand biogenesis of cranial sutures, nor the mechanisms that translate transduction from mechanical stretch of the expanding brain to growth and maintenance of sutural patency. To explore this we are using single cell transcriptomics of cranial sutures, combined with analysis of craniosynostosis models generated using CRISPR/Cas9-based gene targeting.