Grant: Research Tools and Instruments

Differential scanning calorimetry (DSC) is powerful biophysical technique for measuring the thermodynamic parameters of protein and nucleic acid unfolding. DSC techniques can also be used to measure binding affinities over a very wide range, from very weak to very tight binding. The requested differential scanning calorimeter is a vital component to the research program of three faculty members at York University who will use DSC methods in a wide range of biochemical applications from studying the folding and binding of DNA aptamers, applying this information to design more selective and sensitive aptamers for use in biosensing; to studying the stability and association of proteins involved in neuron function and in bacterial conjugation (lateral gene transfer). The requested instrument will also be capable of performing pressure perturbation calorimetry (PPC) experiments. PPC experiments enable the measurement of the change in volume of a biomolecule upon ligand biding. This technique is critical to understanding the ligand-induced folding mechanism commonly exhibited by aptamers, which in turn will enable the development of improved aptamers by maximizing the volume change upon ligand binding. No instrument with similar capabilities is available at York or at nearby universities which makes the acquisition of this instrument essential to the research and training program of the applicants. All current (11) and future highly qualified personnel (HQP), from the three different research laboratories will be trained in the use of this state-of-the-art instrument and be able to take advantage of this valuable biophysical method. DSC instruments are widely used in industrial settings such as material sciences, agrochemicals the pharmaceutical industry where they are used to study the stability of protein-based therapeutics as well as the formulation of vaccines. Experience in utilizing this instrument will enable the HQPs to fit in well in this sector. For those HQP that will advance their careers in academia their experience using a DSC will enrich their future careers.