Low-volume ITC for investigating biomolecular interactions

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Several researchers at the Université de Montréal are investigating important macromolecular complexes and together have formed an NSERC-funded CREATE training program entitled "Cellular dynamics of macromolecular complexes" (CDMC). This CREATE program is designed to train highly qualified personnel for employment in a number of job sectors, including pharmaceutical and biotech industries. The macromolecular complexes being investigated are important in regulating biological processes such as transcription, RNA processing, glycolysis, viral infection, antibiotic resistance, ion-transport through membranes and cancer. In order to fully understand the role of specific interactions within these important macromolecular complexes, it is crucial to thoroughly characterize both the binding affinity and the specificity of complex formation. Over the last several years, there have been a number of significant technical advancements in measuring the binding affinities of macromolecular complexes. However, isothermal titration calorimetry (ITC) is one technique that allows direct measurement of true binding affinity since it does not require any modification of the molecules of interest and the measurements can be done in solution. The main disadvantage of ITC experiments with standard microcalorimeters is that, when measuring weak binding interactions, large quantities of sample material are needed, and this can often be prohibitive. As a result, low-volume ITC instruments have recently been developed. Low-volume ITC instruments not only significantly minimize the amount of sample required, but also increase sample throughput. These low-volume microcalorimeters are essential for studying interactions when the binding is weak and when sample material is either difficult to obtain or expensive. The requested low-volume microcalorimeter will help fulfill a pressing need for recording ITC experiments of macromolecular complexes and for training students and postdoctoral fellows as part of the CREATE-CDMC program.