The focus of the Mann laboratory is to understand how metabolism drives cell fate decisions. We use the complex cellular diversification of inner ear sensory epithelia as a model system. At the heart of these epithelia are sensory hair cells, highly specialised mechanoreceptors that detect sounds and accelerations. There are currently no biological therapies to replace hair cells once damaged, making hearing and balance disorders difficult to treat. Although it is possible to generate new hair cells in vitro, we do not understand the specific factors needed to drive their functional diversity, in particular how their frequency responses are specified and tuned.

We hypothesize that cellular metabolism is a key determinant underlying these processes during inner ear development. Using a combination of imaging techniques including fluorescence lifetime imaging of NAD(P)H and FAD, live time-lapse, super-resolution and electron microscopy, we are investigating the role of metabolism in hair cell formation and functional refinement using both mouse and avian models. Current projects in the lab are investigating: (i) the unique metabolic properties of different hair cell types; (ii) how metabolic activity regulates developmental acquisition of tonotopy in hair cells along the cochlea; (iii) how interactions between metabolic and developmental pathways shape hair cell physiology (iv) changes in mitochondrial physiology and ultrastructure in developing hair cells. Our work is funded by the BBSRC.