Our Division has a strong focus on understanding and treating human bone and joint diseases. The Bone Research group collaborates with the Engineering department on state-of-the-art methods to diagnose osteoporosis and osteoarthritis with 3D imaging. Their novel methods have been used to identify focal bone defects that lead to hip fracture, and to determine the beneficial effects of various new drugs and exercise regimens on bone health. With researchers from Bristol, they study the genetics of excessively high bone density, and have discovered a family from Cambridge with mutations that disrupt the binding of an important bone protein called sclerostin. These mutations cause the family members to have some of the highest bone density measurements ever recorded. Using 3D imaging the team have mapped the effects of clinical blockade of the same sclerostin protein in 24 women with low bone density, showing that the drug increased vertebral bone density by almost a quarter within one year. Our division offers a bone histomorphology service and at the time of writing, more than 20 clinical trials are being conducted by the Rheumatology Research Unit ranging from phase IIa to IV.
We have also identified the role of these stress signals in pathogen responses by experiments with Chlamydia trachomatis, a pathogen that imparts a large burden to society by significantly contributing to the prevalence of sexually transmitted diseases, infertility and preventable blindness. Again, we find a role for endoplasmic reticulum stress, which has allowed us to understand some of the fundamental mechanisms of how chlamydia activates this pathway. Using multiplexed proteomic techniques that allow the relative abundance of chlamydia and host proteins to be determined accurately we now have the first opportunity to interrogate the chlamydia-host protein response and closely inspect their interaction. This enables us to further address how chlamydia activates the cellular stress pathways and potentially develop new strategies to overcome this burden.