Contact me on 03 8341 6422 or john.bateman@mcri.edu.au to discuss how projects could be tailored to your specific research interests and to arrange a visit to our laboratories.

BSc (Hons) and PhD scholarships are available.

The cell biology of protein misfolding (ER stress) in genetic cartilage and bone disease
Inherited cartilage disorders affecting growth and joint function are a significant disease burden. Gene mutations have been defined, but our knowledge of the molecular mechanisms of how these mutations cause the disorders, and ultimately how these mechanisms could be therapeutically manipulated, is only just beginning to be explored. We have a major laboratory research program exploring how protein misfolding mutations cause cartilage and bone disease. Our research so far has shown that these unfolded proteins can cause cellular stress and activate intracellular signalling and degradation pathways (proteasomal and autophagy) that have profound effects on gene expression and cellular pathology (see Bateman et al., Nature Reviews Genetics 2009 Mar;10(3):173-83). Several projects are available which will explore the molecular signalling pathways and disease mechanisms using cutting-edge biochemical, molecular biology, cell biology (eg confocal microscopy) and proteomic analysis on cells transfected with mutant genes, and cells and tissues from mouse models. These studies will also explore the use of new therapeutic agents in cell culture to overcome protein misfolding and cell stress.

microRNAs in arthritis
Arthritis is a major healthcare problem, costing A$24 billion pa in clinical care and disability. While the crucial pathology in arthritis is the progressive destruction of articular cartilage, the molecular mechanisms of the initiation and progression of cartilage destruction are not clear. microRNAs (miRNAs) are a recently discovered class of small noncoding RNAs with important roles in post-transcriptional gene regulation in an expanding number of developmental and disease situations. We have identified several miRNAs involved in joint degeneration in osteoarthritis. This project will explore the biological targets of these using cell transfection and expression analysis by next generation sequencing (RNA-Seq)/microarrays and quantitative proteomics. These studies will provide new insights into disease mechanisms, identify biomarkers useful in monitoring disease progression and response to treatment, and will open up new possibilities for therapeutic intervention.

The use of induced pluripotential stem cells (iPSC) for functional genomic analysis of human genetic disease
The ability to generate human pluripotent stem cells from patient tissues and to differentiate these into therapeutically important cell lineages is an exciting new approach for the development of in vitro disease models and for the study human gene function. The goal of this project is to generate patient cartilage and bone cells from blood cells and fibroblasts using induced pluripotential cell (iPSC) technology to study the details of how human mutations cause pathology in vitro, and test new therapeutic agents. During the course of this project students will acquire skills to produce iPSC, characterise them and differentiate them into the target cell types. Experiments will be analysed using a variety of techniques including quantitative PCR, flow cytometry and a wide range of cell biology and biochemical approaches.

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John Bateman

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Department of Paediatrics

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John Bateman

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Faculty of Medicine, Dentistry and Health Sciences

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