Characterization of bio-molecular interactions and investigation of catalytic mechanisms of bio- and chemical catalysts by micro-Isothermal Titration Calorimetry

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In this proposal, we aim to establish an infrastructure for characterization of biomolecular interactions, catalytic mechanisms of bio and chemical catalysts and engennering of "smart" molecular surfaces. We are requesting a micro Isothermal Titration Calorimeter (microITC). Isothermal titration calorimetry measures the heat released from biological and chemical reactions. The sensitivity of the requested microITC is such that it will enable characterization of reactions that have high to low heat release and binding affinities from 103 to 1012 M-1. Hence, it enable characterization of a wide range of interactions such as those between DNA-transcription factors, which normally have binding affinities at nanomolar range, as well as protein-protein/peptide/small molecules interactions that normally have binding affinities from low micromolar to high micromolar. At the same time, the high sensitivity of such instrument would enable for quick screening of aptamers and small libraries of small molecules as well evaluation of the efficiency of delivery of modified lipids to cells . Based on these capacities this instrument will greatly enhance the current research capabilities of the applicants of this proposal to study, but not limited, to bacterial response to cell wall stress, antibiotic resistance, formation of protein-based nanotubes and biocells, mechanism of the on-set of Alzheimer's disease, identification and development of drugs and design and development of chemical catalysts and engineering of "smart" surfaces for controlling of stem cell differentiation. These research areas are essential to the economy and health of Canadians. As many as 35 high quality personnel (HQPs), coming from six different research laboratories, will be trained in this state-of-the-art instrument. Utilization of this instrument in industrial settings will enable the HQPs to be fit well in this sector. As well, for those that will advance their careers in academia, the gained expertise, will enable them to advance other research areas and train more HQPs.