Grant: Discovery Grants Program - Individual

The understanding of sequence-structure-properties relationships in proteins has never been so important as in this post-genomic era. Currently, protein purification and characterisation is dramatically outpaced by the volume of DNA sequence deposited in various databanks, and our inability to predict protein behaviour using genome sequence information drastically slows the pace of discovery. By improving our understanding of sequence motifs or signatures that control enzymatic properties, we will allow the accurate extraction of protein character information from genomic data, and thus accelerate innovation in various fields, such as medical research, nutrition, drug synthesis and a number of water-based industrial processes. This is why several labs, including ours, continue their basic research on protein sequence encoded information. Investigation of carboxylesterases (""lipase"") revealed that such enzymes might be well suited for achieving our fundamental goal which is the elucidation of sequence-structure-properties relationships in proteins. Because of their relatedness, Bacillacae carboxylesterases share a very similar 3D organisation, yet display large differences in their properties. Our short-term objectives are to identify putative sequence motifs that might be associated with a specific property of an individual carboxylesterase. Then related carboxylesterases will be modified by genetic means in order to demonstrate the relationship between the putative motif and the enzyme property. For that an array of molecular biology and bioinformatics tools will be used, along as robotised high-throughput enzymatic analyses under various conditions. Our long term objective is to elucidate sequence-structure-properties relationships in order to improve our ability to predict features of putative carboxylesterases, and more generally lipases, suggested by genomic annotation. Further, with this new knowledge, we hope to help protein engineers in the development of customised enzymes for novel industrial applications.