UNDERSTANDING GENETIC VARIATIONS IN BONE

Summary

Functional genomics is a field that is undergoing major changes in practice due to the accessibility of gene editing technologies. Our team has developed methods for gene editing in cultured human bone cells and is currently establishing translational testing methods for examining gene variations associated with human genetic bone diseases. This project will teach the candidate cutting-edge skills in osteoblast culturing and differentiation, gene editing using CRISPR-Cas9 technology, and assays for characterising changes in gene expression and mutation analysis. The candidate will work with both basic scientists, hospital scientists, and clinicians who are managing children with brittle bone diseases.

Supervisor(s)

Associate Professor Aaron Schindeler, Associate Professor Craig Munns

Research Location

Westmead - Kids Research Institute

Program Type

Masters/PHD

Synopsis

This project involves the culture of immortalised human mesenchymal stem cells with the potential to be differentiated into an osteoblastic phenotype. The candidate will initially use established methods to generate loss-of-function mutations in genes associated with disease, before moving on to create variants of uncertain significance obtained from patient sequencing. This will involve PC2 cell culture methods and CRISPR-Cas9 gene editing. As this field is moving rapidly, it is expected that the technologies and approaches used for gene editing will evolve during the project and become increasingly efficient. Gene edited cell lines will be tested in established osteogenesis assays as well as other biochemical assays for bone cell function. The student will be given opportunities to develop new assays and examine a range of biomarkers. The goal is to transfer these discoveries into the established hospital Molecular Genetics laboratory workflow for patient diagnostics. 
The resultant gene modified cell lines will also be a valuable resource for examining the mechanisms of brittle bone diseases and testing new therapeutic options. These can involve both pharmacotherapies and gene therapy approaches. 
We are seeking motivated students interested in developing their technical skills and wishing to make a difference in the lives of children with severe genetic disorders. This project is ideal as a PhD project, but a modified version of a Masters project could be a possibility. A strong candidate will be able to work as part of a multidisciplinary research team and have strong written/oral communication skills. The capacity to attract an independent scholarship (first class honours, prior publications) will be looked upon extremely favourably.

Additional Information

For more information contact A/Prof Aaron Schindeler at aaron.schindeler@sydney.edu.au or +61 2 98451451.

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Keywords

Bone, gene editing, osteoblast, Osteogenesis Imperfecta, functional genomics

Opportunity ID

The opportunity ID for this research opportunity is: 2870

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