Determining how healthy, physiologically-relevant exposure to inflammatory factors affects chondrocyte secretory and post-transcriptional responses.

Healthy cartilage in our joints is essential for us to maintain an active life into old age. The cells that maintain cartilage are called chondrocytes and have a specialised phenotype that is initiated during development and then maintained throughout our lives. Successful maintenance of the chondrocyte phenotype is important for healthy ageing, whilst improved understanding of phenotype induction is extremely important when trying to engineer fresh tissue.

Our groups are interested in how post-transcriptional gene regulation influences cartilage function, in Liverpool our research is particularly focused on the importance of variation in messenger RNA (mRNA) decay or protein translation rates. This project offers an exciting opportunity to experimentally examine how post-transcriptional regulatory mechanisms contribute to cartilage cell function through the use of cutting-edge gene editing approaches. The work will focus on the chondrocyte response to inflammatory mediators at levels normally observed in healthy joints or those that have suffered acute mechanical stress. This is a novel area because inflammatory factors are usually employed in chondrocyte studies at unnaturally high levels to generate tissue breakdown and model disease. This project aims instead to determine the processes modulated by such factors in at concentrations relevant to the healthy tissue environment.

The project will use Crispr/Cas9 methodology to disrupt important inflammatory signalling process to determine the primary and secondary responses of chondrocytes to physiologically-relevant levels of exposure to inflammatory factors. The work will characterise how these responses are mediated at the molecular level, examining transcriptional, post transcriptional and secretory responses.