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Developing therapies for osteoarthritis and chondrodysplasias


Project Description

Recent work from our lab and others has shown that Endoplasmic Reticulum (ER) stress plays an important role in the disease mechanisms associated with some forms of dwarfism and potentially also in osteoarthritis. These diseases are caused by changes in the development and or maintenance of cartilage as a result of, at least in part, increased ER stress in chondrocytes. The aim of this project is to identify new ways of alleviating ER stress in chondrocytes and testing these potential new therapies in model systems in vivo.

The project will utilise both cell culture and gene targeted mouse models and will employ a range of modern molecular, biochemical, genetic and histological techniques. Applicants must have a strong academic background in life sciences and some relevant research experience in either mouse genetics or cell culture. The successful applicant will be required to hold a Home Office Licence

Funding Notes

This project has a Band 3 fee. Details of our different fee bands can be found on our website. For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website. Informal enquiries may be made directly to the primary supervisor.

References

• Kung L, Rajpar MH, Briggs MD, Boot-Handford RP (2012) Hypertrophic chondrocytes have a limited capacity to cope with increases in endoplasmic reticulum stress without triggering the unfolded protein response. J. Histochem. Cytochem. 60, 734-748.
• Cameron TL, Bell KM, Tatarczuch L, Mackie EJ, Rajpar MH, McDermott BT, Boot-Handford RP, Bateman JF. (2011) Transcriptional Profiling of Chondrodysplasia Growth Plate Cartilage Reveals Adaptive ER-Stress Networks That Allow Survival but Disrupt Hypertrophy. PLoS One. 2011;6(9):e24600.
• Boot-Handford RP, Briggs MD (2010) The unfolded protein response and its relevance to connective tissue diseases. Cell Tissue Res. 339, 197–211
• Rajpar MH, McDermott B, Kung L, Eardley R, Knowles L, Heeran M, Thornton DJ, Wilson R, Bateman JF, Poulsom R, Arvan P, Kadler KE, Briggs MD, Boot-Handford RP (2009) Targeted Induction of Endoplasmic Reticulum Stress Induces Cartilage Pathology. PLoS Genet. Oct;5(10):e1000691.
• Bateman JF, Boot-Handford RP, Lamandé SR (2009) Genetic diseases of connective tissues: cellular and extracellular effects of ECM mutations Nat. Rev. Genet. 10(3), 173-83

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