The elucidation of 3-dimensional structures of proteins and other biological macromolecules and complexes is essential for rational drug design, targeting and delivery, biocatalysis, the design of environmentally friendly agrochemicals, the development of biosensors and other nanobiotechnological applications. The most powerful tool for structural analysis is X-ray crystallography, which crucially depends on growth of high diffraction quality crystals. Crystallisation is the least controllable and usually rate-limiting step of the process that goes from cloning a gene to using the structural information for predicting and designing function. TOPCRYST, an academia-industry project, will use Dual Polarimetric Interferometry, pioneered by Farfield Scientific Ltd., to probe crystallisation at its earliest, most crucial stages. This will allow to predict the outcome of crystallisation trials when they are still at their earliest stages and thus to rationally design such experiments in order to lead them to the desired result, i.e. well-diffracting crystals. Transfer of knowledge between academia and industry will tackle the problem of detecting crystal nucleation phenomena at the very earliest stages of crystallisation and holds a number of promises that will be investigated in its course: (i) to guide the choice of pH and buffer, temperature, precipitating agent, additive(s) etc, starting from a limited number of preliminary experiments, thus obviating the need for extensive screening; (ii) to allow to unequivocally distinguish crystalline from amorphous material, something which is not always easy even for an experienced crystalliser, with obvious possibilities of extension to high-throughput environments; (iii) to allow optimisation of conditions under real-time control; (iv) to provide an experimental underpinning to the theoretical understanding of nucleation phenomena (v) to develop novel instrumentation for crystallisation of macromolecules.
Call for proposal
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Funding SchemeMC-IAPP - Industry-Academia Partnerships and Pathways (IAPP)
CWI 6GU Crewe