Prof. Martin Knight. The role of Primary cilia in development, health and disease.
Date: 2 April 2014 Time: 15:00 - 16:00
Martin Knight's research concerns the area of mechanobiology and how living cells and tissues respond to mechanical forces in terms of their biomechanical properties and regulation of intracellular signalling. This is essential for the health and functionality of many tissues and therefore has potential application in various medical therapies from tissue engineering and regenerative medicine to pharmaceuticals. Studies are examining a variety of cell types including tendon cells, neurons, cancer cells and mesenchymal stem cells. However the majority of his work has focussed on articular chondrocytes and the role of mechanobiology in the development and treatment of arthritis.
The presentation will focus on my groups work looking at primary cilia structure and function and how this is influenced by stem cell differentiation, disease and extracellular physicochemical stimuli. Primary cilia are microtubule-based structures, 1-4 microns in length, with one cilium per cell. Primary cilia function as a signalling hub regulating a variety of intracellular pathways including mechanotransduction, wnt and hedgehog signalling. Primary cilia are expressed by vast majority of cell types including chondrocytes, tenocytes, osteocytes, neurons, endothelial and epithelial cells and stem cells.
In 2012 we published the first paper showing that primary cilia are required for cartilage mechanotransduction and up-regulation of proteoglycan synthesis (Wann et al, FASEB, 2012). More recently we have shown, for the first time, that primary cilia are involved in the inflammatory response to cytokines such as interleukin-1 (Wann and Knight, CMLS, 2012) and sequestration of HIF-2a to the cilium (Wann et al, Cilia 2013). We have also shown how cilia length is regulated by environmental factors including heat shock (Prodromou et al, J Cell Sci, 2013), mechanical loading (Thompson et al, OA and Cart, 2014) and topography (McMaurray et al, Sci Reports, 2013) and how these changes in cilia length modulate key signalling pathways including wnt and hedgehog signalling. Furthermore we show that modulation of primary cilia structure and associated signalling ultimately effects tissue structure and biomechanics (Irianto et al, J Biomech, 2014)
All these studies add to the growing evidence of the fundamental importance of primary cilia in development, health and disease.