Unravelling the role of a serine proteinase inhibitor (serpin) as a gatekeeper to chondrogenic differentiation of mesenchymal stem cells

This project is an opportunity for a talented student to perform exciting research into how cartilage is formed from mesenchymal stem cells (MSCs). The developing skeleton is initially made of cartilage, which gradually calcifies to become bone. Cartilage is formed by a process known as chondrogenesis, involving the condensation of MSCs in high density and differentiation into chondrocytes which deposit a complex cartilage matrix. Establishing critical regulators of cartilage formation is important, not just to understand development, but also has the potential to aid tissue engineering strategies for joint diseases such as osteoarthritis.

We have identified a serine proteinase inhibitor (serpin), which is rapidly induced during MSC differentiation into chondrocytes. Crucially, when the expression of this gene is silenced, cartilage formation and the expression of cartilage genes is greatly reduced, demonstrating that this serpin plays a key role in chondrogenesis. Serpins are usually involved in the inhibition of proteinases, however many have non-inhibitory roles. In this project, we seek to understand the important role this serpin plays in cartilage development, what drives its expression, and whether harnessing this can improve the structural and physical properties of engineered cartilage.

The project will use a combination of cutting edge molecular biology tools such as CRISPR/Cas9, along with well-established techniques such as stem cell differentiation, chromatin immunoprecipitation and microscopy. The project will be supervised by Dr David Wilkinson (University of Liverpool) who is an expert in cartilage biology, the extracellular matrix and proteinase inhibitors. The Institute of Life Course and Medical Sciences (ILCaMS) provides the ideal setting for this research, housing superb facilities including dedicated tissue cultures, microscope and histology suites, and ample laboratory and office space. The Institute hosts a range of expertise which are complimentary to this work making the department both a productive and exciting place to do research. The student will also spend a 3-month research-stay at Newcastle University, in the laboratory of Professor David Young who has strong expertise in chondrogenesis mechanistic studies, while the properties of engineered cartilage will be measured with the support of Professor Kenny Dalgarno.

Importantly, the student will benefit from a positive and supportive supervisory team. Postgraduate students at Liverpool join an active, diverse and engaged community and their training is strongly supported by the Liverpool Doctoral College. The project is suitable for a holder of a BSc (2:1 or above) in Molecular Biology, Biochemistry or a related Biological Sciences discipline. 

Informal enquiries may be made to david.wilkinson@liverpool.ac.uk

HOW TO APPLY

Applications should be made by emailing bbsrcdtp@liverpool.ac.uk with a CV and a covering letter, including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project/s and at the selected University. Applications not meeting these criteria will be rejected. We will also require electronic copies of your degree certificates and transcripts.

In addition to the CV and covering letter, please email a completed copy of the Application Details Form (Word document) to bbsrcdtp@liverpool.ac.uk, noting the additional details that are required for your application which are listed in this form. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.