Investigating genetic components of cerebral palsy

Cerebral palsy (CP) is a physical disability that affects movement and posture. CP is the most common physical disability in childhood, but the underlying causes are poorly understood. Current knowledge suggests the origins of CP are multifactorial, with a substantial body of evidence indicating that many with CP have an underlying genetic disorder. Recent genome-wide studies from Australia and around the world in CP have identified plausible causative genetic changes in around 20-37% of affected individuals. This project is about extending our understanding of the genomic causes of CP and unites clinical, genomic and laboratory expertise from across the world. Through existing collaborations with the International Cerebral Palsy Genomics Consortium; ICPGC, we have identified genomic targets via whole-exome sequencing studies and aim to develop a platform for rapid functional screening of genomic CP candidates in zebrafish (Danio rerio). Understanding the mechanistic pathways to human disease requires cellular and molecular modelling. Zebrafish are a valuable tool in developmental neurogenetics because, the cell types, physiology and neurogenetics are broadly orthologous to the human central nervous system. Recent advances in genomics and genome-editing technique have made the zebrafish a prime model to study and model human genetic diseases. Compared to other vertebrate models, the brain of the zebrafish is visible during development enabling simple phenotyping regarding the onset and progression of pathological processes. We will take full advantage of the zebrafish model to functionally model CP candidate genes and reveal underlying cellular and molecular mechanisms.