Research is focused on the relationship between the conformational motions of proteins in solution (their dynamics) and their biological activity. The primary tool is Time- Resolved Electrospray Mass Spectrometry, a method that allows a wide range of active biochemical processes to be monitored on short (millisecond-to-second) timescales. This technique is combined with a number of other techniques, including biophysical NMR and H/D exchange to obtain a highly detailed, dynamic picture of protein function. There is also a significant technology development component to the work.
Dr. Wilson employs advanced Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR) spectroscopy methods to uncover structures of proteins in their active conformations, which often do not coincide with the shapes of the proteins in their common, lowest energy states. To detect proteins in their various states of motion, Dr. Wilson makes use of microfluidic devices with online coupling to ESI-MS, allowing for the measurements to be performed very rapidly and in a high throughput manner. Another aspect of Dr. Wilson’s research deals with understanding the formation of amyloids, a specific form of protein aggregates that are implicated in such diseases as Alzheimer’s and Parkinson’s. Dr. Wilson’s group is carrying out high resolution studies of the interactions leading to amyloidosis in the Transthyretin peptide TTR105-115. His approach involves the use of Saturation Transfer Difference (STD) NMR spectroscopy to map out the specific residues most tightly associated with amyloid formation. Such fundamental research into the mechanisms of amyloidosis is a critical first step to the rational design of amyloid inhibitor drugs.
Rob T, Gill P, Golemi-Kotra D, Wilson DJ, "An electrospray ms-coupled microfluidic device for subsecond hydrogen/deuterium exchange pulse-labelling reveals allosteric effects in enzyme inhibition", Lab on a Chip, 13(13), 2528-32.
Liuni P, Zhu S and Wilson DJ, (2013) "Oxidative Labeling with Mass Spectrometry for Studying Protein Structure, Folding, and Dynamics", Antioxidants and Redox Signalling, (in press).
Sljoka A and Wilson DJ, (2013) "Probing Protein Ensemble Rigidity and Hydrogen-Deuterium exchange", Physical Biology, 10(5):056013 (E-pub ahead of print).
Resetca D and Wilson DJ, (2013) "Characterizing rapid, activity-linked conformational transitions in proteins via sub-second hydrogen deuterium exchange mass spectrometry", FEBS Journal, 280(22), 5616-5625, front cover feature.
Liuni P, Olkhov-Mitsel E, Orellana A and Wilson DJ, (2013) "Measuring Kinetic Isotope Effects in Enzyme Reactions Using Time-Resolved Electrospray Mass Spectrometry", Analytical Chemistry, 85(7), 3758-64.
Peter Liuni, Araby Jaganathan and Derek J. Wilson (2012) "Conformer Selection and Intensified Dynamics During Catalytic Turnover in Chymotrypsin", Angewandte Chemie Int. Ed., 51(38), 9666-9669.
Tamanna Rob, Peter Liuni, Preet Kamal Gill, Shaolong Zhu, Naresh Balachandran, Paul J. Berti and Derek J. Wilson (2012) "Measuring Dynamics in Weakly Structured Regions of Proteins Using Microfluidics-Enabled Subsecond H/D Exchange Mass Spectrometry", Anal. Chem., 84(8), 3771-3779.