Grant: Discovery Grants Program - Individual

Therapeutic agents interact with a variety of physiological molecules in the human body; their overall biological effect is determined by the combination of these interactions. The proposed research program will focus on drug-protein interactions, as proteins are often the targets of drugs, and may serve as their transporters or receptors. More specifically, the short-term objective of the research program is to gain deep understanding of the interaction of a widely used anticancer agent (paclitaxel, trade name: Taxol) and a plasma protein (human serum albumin). This interaction is not only important for the transport of paclitaxel but is also of particular interest as albumin is known to be taken up by tumours at an increased rate in comparison to normal tissue. A powerful combination of computational and experimental methods (including cutting-edge technology based on surface plasmon resonance) will be used to explore the mechanism of the interaction, to identify the primary drug binding site on the protein, and to reveal how this interaction affects the binding of physiological ligands (such as long-chain fatty acids) and other drugs to albumin. The long-term objective of the research program is to tackle the challenge of exploring the interaction of anticancer drug-albumin complexes with albumin binding proteins and with receptors on the surface of tumour cells. Fundamental understanding of biomolecular interactions will lead to new therapeutics with greatly improved characteristics that will benefit the public in and outside Canada. The new knowledge generated through successful accomplishment of the short- and long-term objectives is expected to prompt research activities in protein chemistry and related fields, and thereby contribute to their advancement. Participation in the research program will provide excellent interdisciplinary training opportunities for future scientists.