Mass spectrometry of proteins

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This proposal is for research in mass spectrometry applied to the study of proteins. Mass spectrometers are scientific instruments used to detect and identify trace substances. In mass spectrometers, molecules are electrically charged to form "ions" and the ions are then separated in vacuum according to their ratios of mass to charge. Only recently has it become possible to make ions of large protein molecules, like hemoglobin, and inject them into vacuum. The fundamental work proposed here will examine the properties of ions of proteins in vacuum and compare them to the properties of the proteins in solution, where they carry out their normal biological functions. In some cases, proteins in a vacuum can retain their solution properties. If this is generally true, then mass spectrometers can be uses to study binding of proteins to other species in a fast, sensitive specific way. Specifically we will examine the properties of hemoglobin ions, and the effects on these properties of mutations to Hb that cause disease. The properties of a class of small-molecule drugs called "molecular chaperones" binding to proteins in vacuum will be investigated. Mass spectrometry may provide a new method to identify chaperone molecules. The reaction of carbon dioxide with proteins like hemoglobin will be studied. This has long been known to be a possible method of transport of CO2 in blood, but has not been quantified in detail. Finally we will investigate the effects of adding controlled numbers of water molecules to protein ions, to determine the effects on folding of the protein ions. This work will lead to new approaches to study proteins for applications in medicine, pharmacy and biotechnology. Canada will benefit in at least two ways. The proposed work will train students and postdoctoral fellows in a field where there is a strong demand for such highly qualified personnel. Any intellectual property will be owned by the University of British Columbia, and thus will remain in Canada.