High throughput bio-layer interferometry at Dundee for anti-microbial and interaction studies.

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Proteins are at the centre of almost all the molecular processes that are important for the survival of the living cell, be that cell a free living microbe or part of a vital organ in a complex animal. The number and amount of different proteins in a cell is staggering but in order to successfully carry out their biological function, proteins must interact with exquisitely specific protein or chemical partners. Sometimes, forming a higher-order complex with other proteins is the central event to the biological process in question. Sometimes, proteins do not interact with other proteins at all but instead bind with small molecules, or other macromolecules such as nucleic acids, lipids or carbohydrates, before they can carry out their biological function. Understanding how proteins interact with other molecules is central to our basic understanding communication and signalling at the molecular level. Physicists, working in collaboration with biologists, chemists and mathematicians, have devised many techniques for measuring and quantifying molecular interactions. One relatively new technique is called bio-layer interferometry. In this technique a tiny fibre optic thread has a protein-of-interest attached to its tip. When this tip is dipped in a solution that contains a molecule that will interact with the protein-of-interest the optical properties of the fibre change and this can be recorded by the instrument. The data generated can therefore give brand new fundamental information on how proteins operate. On the other hand, this instrumentation can also be of use in exploring for different chemicals that might disrupt protein-protein interactions or stop a protein from working altogether. The optical fibres are so small that they can be arranged in arrays of up to 96 fibres at a time. The fibres can then be dipped in hundreds of different chemicals over the course of a few minutes and that way huge 'chemical libraries' can be searched for random molecules that bind. From that narrowed-down set of interactors, it may be possible to find some that inhibit the activity of the protein-of-interest. So-called chemical 'inhibitors' that disrupt key cellular pathways are of critical importance in modern cell biology research projects, where they are used to understand fundamental aspects of cellular physiology. At Dundee, we also wish to use this instrument to search for molecules that might inhibit key process in microbial metabolism - and so help underpin the global search for new anti-microbials.