Investigating the role of FBX proteins in Neurodevelopment

Research Opportunity
PhD students
Department / Centre
Royal Children’s Hospital/Murdoch Childrens Research Institute
Primary Supervisor Email Number Webpage
Dr Sarah Stephenson Personal web page
Co-supervisor Email Number Webpage
Prof Paul Lockhart
Dr Jordan Wright

Summary Investigating the role of FBX proteins in Neurodevelopment

Project Details

Neurodevelopment is a complex spatiotemporal process requiring the coordinated action of genetic and environmental cues to regulate a multitude of developmental processes, including cellular proliferation, differentiation, migration, and formation of neural circuits. F-box (FBX) proteins are essential for regulating the ubiquitination of proteins involved in the cell cycle.

We recently identified monoallelic loss of function variants in FBXW7 that cause a novel neurodevelopmental syndrome characterised by global developmental delay, borderline to severe intellectual disability, hypotonia, and gastrointestinal issues. An increasing knowledge of the phenotypic and functional overlap between neurodevelopmental disorders has shifted the paradigm from genetic disorders as discrete entities towards continuums of molecular subgroups. FBXW7 is the sixth gene encoding an FBX protein that has been found to cause a neurodevelopmental disorder, and many overlapping clinical features are recognised suggesting a shared underlying mechanism. It is an exciting and feasible prospect that a limited number of agents targeting shared mechanisms underlying multiple subgroups of NDDs may ultimately be used to treat a broader set of neurodevelopmental disorders.

In this project, we will generate human induced pluripotent stem cell (iPSC)-derived neurons harbouring monoallelic loss of function mutations in four FBX genes (FBXO11, FBXO28, FBXW7 and FBXW11). To do this we will use allele specific CRISPR/Cas9 gene editing technology and rapid neuronal induction methods to obtain active, mature neural cultures within 4 weeks. Neurons will be characterised using live-cell imaging using virally delivered fluorescent reporters and calcium indicators to assess cell proliferation, synaptogenesis, maturation, neurite extension and activity, and biochemical assays to assess changes in ubiquitination during neuronal development.

Faculty Research Themes

Child Health

School Research Themes

Child Health in Medicine

Research Opportunities

PhD students
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department / Centre


Research Node

Royal Children’s Hospital/Murdoch Childrens Research Institute

MDHS Research library
Explore by researcher, school, project or topic.