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Exploring mechanism in chemical biology by high-throughput approaches

Final Report Summary - CHEMBIOMECH (Exploring mechanism in chemical biology by high-throughput approaches)

In the biomedical sciences, where endless combinatorial diversity of genes, proteins and synthetic molecules are involved, miniaturisation has not only allowed an increase in the speed at which experiment can be performed: it has given birth to new areas such as combinatorial chemistry and biology, proteomics, genomics, and more recently, to systems and synthetic biology. In all these areas, the synthesis, assay and analysis of large molecular ensembles has become the essence of experimental progress. However, it is the systematic analysis of the enormous amounts of data generated that will ultimately lead to an understanding of fundamental chemical and biological problems.
This proposal has employed libraries of molecules to give such mechanistic insight – into how enzyme catalysis is brought about in proteins and polymeric enzyme models and into the molecular recognition and cell biology of drug delivery reagents. The basis of such insight was possible based on our development of an extremely miniaturised system to 'look' at each member of a molecular library: we employed pico- to nanolitre droplets as equivalents of the proverbial test tube. Such nanodroplets can be made and analysed in microfluidic devices at high frequency (more than a million per hour!) - the enormous amount of information we can gather from insight into the properties of such large examples helps us to navigate diversity space more efficiently than currently possible. At the same time the small droplet size makes this system extremely economical (using approximately a millionfold less reagent) and is relatively easily established in non-specialist settings.