Canada Research Chair in Protein Folding and Biological Mass Spectrometry
Tier 2 - 2004-03-01
Natural Sciences and Engineering
519-661-2111 ext. 86313
Studying protein folding, enzymatic reactions, and noncovalent ligand-protein interactions with the use of mass spectrometry.
The research will contribute to a better understanding of the mechanisms underlying protein-misfolding diseases (e.g., Alzheimer's) and to the development of novel approaches for drug discovery.
Using Mass Spectrometry to Understand How Proteins Fold
Proteins are linear chains of amino acids that fold into highly ordered three-dimensional structures. The folding occurs spontaneously, and the final structure of each protein is determined by its amino acid sequence. Many fundamental aspects of protein folding are still under investigation. In particular, scientists are trying to figure out the relationship between the sequence of amino acids and the final structure of the protein. Also, the actual folding mechanisms (the order of events leading from unfolded conformation to native structure), is still a matter of debate. Research into protein folding has important implications for understanding the mechanisms underlying many disorders including Alzheimer's and "mad cow disease."
Canada Research Chair Dr. Lars Konermann is studying protein-folding mechanisms through experiments that monitor the structure of proteins as a function of time during folding. Particular emphasis is being placed on the detection and characterization of short-lived folding intermediates. Studies of this type are challenging due to the extremely short lifetimes of these species, which are often in the millisecond time range. Dr. Konermann's laboratory uses electrospray ionization mass spectrometry (ESI-MS) together with specialized rapid mixing techniques. This approach has proven to be extremely powerful.
The scientists in Dr. Konermann's laboratory are also carrying out mechanistic studies of enzyme-catalyzed reactions. Enzymes are proteins that act as catalysts; they accelerate the rates of biochemical reactions by many orders of magnitude. In addition, the scientists are trying to develop new methods of monitoring the ways certain molecules (ligands) bind to biological receptor molecules. The detection of specific ligand-receptor interactions represents a crucial step in the discovery and development of new drugs. As such, this research area is of greatest interest to the pharmaceutical industry.