"Extremophilic (extreme-loving) organisms have evolved unique features to enable them to function in extreme environmental conditions. Despite much progress in understanding extremophilic protein structure, there is a lack of quantitative information on the conformational dynamics and flexibility of proteins in extreme environments, information which is crucial to develop an understanding of their functional capabilities. Understanding the physical mechanisms of extremophilic organisms and their remarkable preservation capability is not only of fundamental interest, but also pivotal to our abilities to rationally engineer or re-engineer biological materials for exploitation. This proposal aims to develop quantitative biophysical approaches to characterise the physical mechanisms of protein folding and stability in extreme environments. This is an ambitious program of work with great potential to lead to ground-breaking scientific breakthroughs in the fields of water and aqueous solutions, protein folding and protein adaption in extremophilic environments. A state-of-the-art, custom built force spectroscopy instrument will be used to examine the conformational dynamics of single extremophilic proteins. A newly built, state-of-the-art diffractometer at the ISIS pulsed neutron facility at the Rutherford Appleton Laboratories in the UK will be exploited to uncover details of the structural architecture of extremophilic proteins and their surrounding solvent environment. The development of these methods will deliver fundamental insights into the mechanisms of extreme organisms, in addition to developing research tools that will be exploited in synthetic biology, industry and bionanotechnology. A unique collection of skills, together with a world class team of collaborators from across Europe, gives this proposal unrivalled ability to transform extremophilic protein folding research in Europe."