Tripping the light fantastic: elucidating global protein structural change correlated with chemical change across the femtosecond to second timescale

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At the heart of chemistry lies the process of atomic bond formation and breakage, an event that is very difficult to directly observe due to the extremely fast timescale and the very small nature of the atomic bond. In other words, the construction of a 'molecular camera' that might allow the recording of these fast and tiny events only recently become a reality. The advent of X-FEL (X-ray Free Electron Laser) systems has made the recording of such molecular movies a reality, although this remains an extremely technically challenging feat to achieve. Systems where atomic bond reorganisation is trigger by light are ideally suited as initial subjects for these cutting-edge studies as the researcher (ie the camera man) can control the event through (laser) illumination. We seek to determine how two distinct type of biological photoreceptors respond to light, coupling the initial atomic bond reorganisation to the transient change in protein structure that ulimately leads to a light-driven response by the organism. This will allow us to formulate new models for general protein dynamic behaviour, which will impact the areas of biocatalysis, biomaterials, therapeutic antibodies/protein production and the study of protein dynamic behaviour/misfolding in health and disease. Ultimately, the full characterisation of these photoreceptors will be combined with the rational engineering of these systems to produce a range of variants in terms of their response to light of various wavelenghts/colour. This will produce well-characterised light-responsive parts for control of bio-based production of high-value chemicals. The most desirable way to assert this control is through optogenetics: by using light as a non-invasive and non-toxic switch to modulate gene expression during continuous microbial fermentation, simple control of engineered biosynthetic pathways can be achieved.