Murphy Group | Cartilage Biology and Repair
We are interested in how the cartilage lining our bone ends works.
Cartilage is a connective tissue which provides support and allows for some flexibility of movement.
Since cartilage has no blood supply it is continuously in a low oxygen (i.e. hypoxic) environment. Hypoxia is normally seen as a 'bad guy' since it's implicated in conditions such as stroke and peripheral vascular disease.
However, we've found that hypoxia actually promotes cartilage function by providing a protective cushion, allowing weight-bearing and near friction-free movement of the bones in our joints. We take bits of isolated cartilage and study the cell and molecular details of how it functions.
Our work specialises in understanding the transcriptional and post-transcriptional (microRNA-mediated) regulation of cartilage matrix turnover. We ultimately seek to exploit these pathways for therapeutic advantage by inducing repair of injured and diseased joints.
In the late 1990's Professor Murphy first hypothesised that cartilage (an avascular tissue) may have adapted such that hypoxia, rather than being a stress to the tissue, was actually used to drive its tissue-specific function - this function being elaboration of a mechanically competent extracellular matrix to withstand load-bearing and allow articulation of the joints.
By 2001 Professor Murphy had successfully demonstrated such a response. His hypoxia work has subsequently led to an in-depth investigation of microRNAs and our laboratory has identified key roles for specific microRNAs in normal cartilage function and in disease.
Most recently we are using genome editing technology to investigate microRNA binding sites in target genes. MicroRNAs have great potential for the clinic and multiple trials are underway worldwide for the treatment of various conditions by altering microRNA levels in the body. However, since microRNAs can bind to multiple gene targets, efficacy is difficult to determine and safety remains a huge and unaddressed concern. A new approach is clearly needed.
Latest technology in genome editing enables selective alteration of any gene sequence and we are currently attempting to use this technology (specifically the CRISPR/Cas9 system) to identify individual microRNA target sites in human cartilage cells potentially relevant for osteoarthritis treatment.
Our lab's approach is always to first identify important regulators in human tissue before testing in vivo in animal models - hence greatly increasing clinical significance of the work.