Associate ProfessorAaron Schindeler

Project Opportunities

Title: GENE THERAPY FOR BRITTLE BONE DISEASE

Summary of opportunity:

OI or osteogenesis imperfecta is a congenital bone fragility disorder that results in frequent fractures and a tremendous impact on quality of life. In individuals with severe OI, the condition can be deforming and restrict them to wheelchairs. Our group has developed adeno-associated viral (AAV) vectors able to target bone and are combining them with CRISPR-Cas9 gene editing technology to treat OI. This PhD project will focus on cell culture and preclinical models of bone disease as well as emerging gene therapy approaches. The research findings will have the potential to transform the treatment of patients with OI.

Opportunity synopsis:

This project involves the development and/or use of cell lines gene modified to contain OI patient mutations. Mutations are introduced using CRISPR-HDR. Models of type IV and type V OI are currently being prioritized. Gene rescue studies will be performed in cell lines to maximize editing efficiency and avoid off-target effects. Promising therapies will be next applied to preclinical mouse models with delivery using AAV vectors. Outcome measures will be both genetic and functional, and our laboratory has access to state-of-the-art bone-imaging equipment.

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.

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Project Opportunities

Title: DEVELOPING GENE THERAPY APPROACHES FOR TYPE 1 AND TYPE 2 DIABETES

Summary of opportunity:

Diabetes mellitus affects >10% of Australian adults. It is the leading cause of preventable blindness, end-stage renal failure and non-traumatic amputations, and decreases life-expectancy. Pancreatic β-cells are the only cells in the body which release insulin and the failure of β-cells is fundamental in the development of all diabetes. The aim of this project is to develop technologies for gene delivery to human islets, and to prevent and cure preclinical models of diabetes with gene therapy approaches.

Opportunity synopsis:

This project involves several sub-aims: the generation of AAV vectors that target mouse and human islets; the improvement of β-cell survival by expression of survival factors; and rescue of a diabetic mouse model by genetic modulation of vitamin D signalling. This will use a variety of established technologies to track and measure the efficiency of genetic recombination as well as measure improvements to glucose levels and a diabetic phenotype.

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.

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Project Opportunities

Title: THERAPEUTIC DELIVERY OF GENE EDITING ENZYMES TO MUSCULOSKELETAL TISSUES

Summary of opportunity:

Diseases of the musculoskeletal system – including bone fragility disorders, diseases affecting the growth plate, joint degeneration, and inherited muscle disorders – remain challenging to treat due to the difficulty of delivering therapeutic agents into dense, mechanically active tissues. This project explores the use of advanced viral and non-viral delivery platforms to target gene editing enzymes (e.g., CRISPR-Cas9, base editors) to muscle, bone, and tendon. The project integrates molecular design, vector engineering, and in vivo testing to optimise delivery and editing efficiency. This work has the potential to enable transformative therapies for genetic musculoskeletal disorders.

Opportunity synopsis:

This project focuses on the targeted delivery of gene editing tools to musculoskeletal tissues using adeno-associated viral (AAV) vectors and nanoparticle-based delivery systems. Students will develop and characterise engineered vectors that express CRISPR nucleases, base editors, or prime editors. Therapeutic payloads will be optimised for editing efficiency, specificity, and tissue penetration. In vitro work will utilise musculoskeletal-derived cell lines and organoid cultures, with lead candidates progressing to preclinical testing in murine models of muscle or bone disease. Outcomes will include both molecular endpoints (on-target editing, off-target profiling) and functional recovery metrics assessed by imaging, biomechanics, and histology.

This project is suited to students with an interest in translational gene therapy, molecular biology, or musculoskeletal biology. It is offered as a PhD project, with the possibility of adapting it to a Masters project. Strong candidates will have a foundation in biomolecular engineering and/or molecular genetics, excellent attention to detail, and a willingness to work collaboratively in a cross-disciplinary team.

Co-supervisor Alexandra O'Donohue alexandra.odonohue@sydney.edu.au

For more information contact A/Prof Aaron Schindeler at aaron.schindeler@sydney.edu.au.

----------Current Research Projects----------

• https://www.sydney.edu.au/research/opportunities/3415.html
• https://www.sydney.edu.au/research/opportunities/3416.html