Towards treatment of intellectual disability caused by errors in the chromatin machinery

Research Opportunity
PhD students
Number of Honour Places Available
1
Department
Paediatrics
Location
Royal Children’s Hospital/Murdoch Childrens Research Institute
Primary Supervisor Email Number Webpage
Professor David Amor david.amor@mcri.edu.au +61 3 9936 6404 Personal web page

Summary This project will identify and characterize mutations in the chromatin machinery in infants and children with brain development disorders, delineate human phenotypes associated with these mutations, and characterize the phenotypic, cell biological, molecular and biochemical consequences of the patient-specific mutations in model systems. The longer term objective is to test potential therapeutic interventions in genetic models.

Project Details

Intellectual disability occurs in 2-3% of newborns, for a variety of reasons, including environmental factors, chromosomal abnormalities and mutations in single genes. Intellectual disability results in lifetime dependency on family and societal support, yet traditionally, it has been viewed as an untreatable condition. However, recently it has been recognised that intellectual disability resulting from inborn errors in the chromatin machinery may be treatable. More than 40 genetic syndromes have so far been identified in this category, including Kabuki syndrome, KAT6A syndrome and Kleefstra syndrome. This project will focus on mutations in chromatin factors and chromatin-modifying enzymes found in patients with intellectual disability, because chromatin changes are reversible, and because these classes of molecules are well established as therapeutic targets in other disorders. The project will identify and characterize mutations in the chromatin machinery in infants and children with brain development disorders, delineate human phenotypes associated with these mutations, and characterize the phenotypic, cell biological, molecular and biochemical consequences of the patient-specific mutations in model systems. The longer term objective is to test potential therapeutic interventions in genetic models in vitro, in vivo. We anticipate that the investigation of the role of individual chromatin modifiers will go well beyond a specific syndrome and will provide an understanding of the regulation of gene expression in brain development and plasticity, potentially highlighting therapeutics for patients without mutations in these factors.

We hope to recruit a high quality student wishing to undertake research into genetics and neurodevelopmental disorders. Interested applicants should email Professor David Amor at: david.amor@mcri.edu.au



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

Paediatrics

Research Node

Royal Children’s Hospital/Murdoch Childrens Research Institute

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