Mouse models of congenital neurological disorders
The findings of this project will provide significant contributions to understanding Rett syndrome aetiology and that of related clinical phenotypes and may identify potential downstream targets for therapy.
Rett syndrome is a neurodevelopmental condition affecting girls resulting in severe mental impairment and loss of motor skills, most commonly caused by a mutation in a gene called MECP2. As research progresses other genes have been implicated, such as CDKL5, mutations in which are common in Rett girls who have a high level of seizures from a young age. We have previously characterised our Mecp2-deficient mouse using molecular and behavioural approaches and identified a number of putative target genes whose expression was dysregulated and could potentially contribute to the Rett phenotype. We wish to reinforce and build on these findings by analysing the morphological, behavioural and molecular deficiencies, including testing the activity status of the MECP2 protein and its downstream gene targets in the brains of mice lacking functional Cdkl5 we are currently generating, given the overlap in symptoms seen in patients with mutations of these genes. Comparing the combined molecular pathways affected in Cdkl5 deficient mice which parallel those identified in Mecp2 mutants will highlight conserved mechanisms of phenotype development. A greater understanding of these processes will lead to the development of more effective strategies to minimise or circumvent the symptoms associated with Rett syndrome and of related clinical phenotypes.
Opportunity available for both Honours and PhD students
Methodologies: Cell and molecular biological analyses of protein/gene expression, microarray and proteomic analyses, mouse behavioural analysis.
Eligibility: Honours entry: GPA on track for Hons I / IIA classification
PhD entry: Hons I classification, lab-based research experience would be preferable.
The Children’s Medical Research Institute (CMRI) is an award-winning state-of-the-art medical research facility, with over 100 full-time scientists dedicated to researching the genes and proteins important for health and human development. The CMRI is supported in part by its key fundraiser Jeans for Genes®. Our scientists are internationally recognised research leaders and foster excellence in postgraduate training. CMRI graduates are highly sought after nationally and internationally. CMRI is located at Westmead, a major hub for research and medicine in NSW, and is affiliated with the University of Sydney. Easy to access by public transport. Projects are multi-disciplinary with training in molecular and cellular biology techniques, with some involving mass spectrometry, proteomics, protein-protein interactions, transgenic animals or live cell imaging. We are looking for top quality students who can prove a dedicated interest and enthusiasm for scientific research.
Candidates may apply for a CMRI PhD scholarship, which exceeds the Australian Postgraduate Awards and NHMRC scholarships in value; visit the CMRI website for details.
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The opportunity ID for this research opportunity is: 1044
Other opportunities with Professor Patrick Tam