Novel molecular and clinical aspects of FMR1 in fragile X syndrome with implications for patient management

Research Opportunity
Honours, Master of Biomedical Science
Number of Honour Places Available
1
Number of Master Places Available
1
Department
Paediatrics
Location
Royal Children’s Hospital/Murdoch Childrens Research Institute
Primary Supervisor Email Number Webpage
Associate Professor David Godler david.godler@mcri.edu.au Personal web page
Co-supervisor Email Number Webpage
Doctor Emma Baker emma.baker@mcri.edu.au Personal web page

Summary This project will utilise many of the developed technologies, the vast collection of bio-specimens and clinical data, to characterize the relationship between FMR1 mRNA, FMRP and abnormal ASFMR1 expression with epigenetic and clinical changes in FXS males and females. The primary project outcome will be characterization of the distinct and overlapping molecular pathways associated with ID and ASD features in FXS.

Project Details

Fragile X syndrome (FXS) is a common single gene cause of intellectual disability (ID) and autism spectrum disorder (ASD) features, caused by loss of FMR1 protein (FMRP). FMRP is essential for normal synaptic function and neurodevelopment. While loss of FMRP is thought to be primarily responsible for the FXS phenotype, another gene transcribed in the opposing direction to FMR1, called antisense FMR1 (ASFMR1), may also contribute to the FXS phenotype, but to date, the role of ASFMR1 has not been thoroughly studied.     Over the past 5 years an international study called FREE FX has been led by our team at MCRI. The FREE FX study aims to better characterize the molecular basis of FXS presentations and the variability between affected individuals. To date, more than 130 participants with FXS have been recruited and assessed with a number of neuropsychological assessments and novel experimental methods. Extensive behavioural and parent-reported medical history data, as well as bio-specimens including DNA, RNA and protein lysates have been collected from various tissue types for most participants. Genetic and genomic state-of-the-art technologies have also been developed to accurately detect changes at epigenetic (DNA methylation), RNA and protein levels.This project will utilise many of the developed technologies, the vast collection of bio-specimens and clinical data, to characterize the relationship between FMR1 mRNA, FMRP and abnormal ASFMR1 expression with epigenetic and clinical changes in FXS males and females. The primary project outcome will be characterization of the distinct and overlapping molecular pathways associated with ID and ASD features in FXS. This will result in better understanding of the molecular basis of Fragile X related disorders, and will lead to further validation of our prognostic biomarkers, with the potential to improve clinical practice through earlier diagnosis and better prognosis.



Faculty Research Themes

Child Health

School Research Themes

Child Health in Medicine



Research Opportunities

Honours, Master of Biomedical Science
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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