Identifying the causes of brain malformation in children

Summary Identifying the causes of brain malformation in children

Project Details

The human cortex is the surface of the brain that enables advanced intellectual function. It forms through a series of overlapping steps involving neuronal proliferation, migration and differentiation. Abnormal formation of the cortex causes a group of disorders known as malformations of cortical development (MCD), which can result in epilepsy, intellectual disability and cerebral palsy. These conditions affect ~1:5000 children and there is considerable evidence that gene mutations cause MCD, but to date few of the genes involved have been identified.

This project will utilise modern genomic technologies, including whole exome and genome sequencing, to identify the genetic basis of MCD. Methodology will include gene discovery and characterisation in model systems, including pluripotent stem cells, to determine underlying disease pathogenesis. Close collaboration with neurosurgeons and neurologists at the Royal Children's Hospital Epilepsy Program means that this project is at the interface of clinical and laboratory research, providing outstanding opportunity for patient-facing research with meaningful outcomes for affected families. The collaboration also enables unique access to tissue, facilitating transcriptomic and proteomic analyses of resected brain to investigate relevant disease mechanisms. The successful applicant will work closely with clinicians and bioinformaticians within a large multidisciplinary team.