Grant: Research Tools and Instruments - Category 1 (<$150,000)

The proper functioning of a protein is intimately associated with its ability to recognize and bind to specific target molecules at the right time and with the right affinity. The applicants' research interests are diverse, but nonetheless converge on to the characterization of proteins and their interactions with target molecules such as ions, metal co-factors, small molecules and other proteins in health and disease. To gain a more comprehensive understanding of these interactions one requires detailed knowledge about the associated macromolecular parameters such as the strength, the number of molecules involved, and various energetic coefficients. Isothermal titration calorimetry (ITC) is a proven and robust biophysical methodology that can directly measure these parameters in solution. Moreover, ITC is attractive because it does not require modification of the molecules under investigation, which can potentially disrupt the extent of interaction. Technical advances in ITC design have allowed for significantly reduced sample volumes, allowing for direct measurement of protein-ligand interactions in solution using a microcalorimeter. We are requesting such a device to fulfill a pressing need to explore the structural, biophysical and chemical basis of novel protein interactions at Queen's University. Data derived from these experiments will lead to an improved understanding of their role in cellular function and regulation. Funding of this proposal will provide a continuing opportunity for the high-qualified personnel (HQP) to gain valuable training with one of the most widely used approaches in modern protein structure and function studies. This work will not only expand HQP training and collaborative work in this area of research, but will also position the applicants in making key discoveries that have broader implications in the fields of green chemistry, cellular regulation, and agriculture.