Research Interests
Unprecedented numbers of gene products are now available for study, due to the recent success of large-scale sequencing projects. Characterization of the three-dimensional structures of these proteins is an important part of the ongoing revolution in molecular biology, in new research areas called proteomics, functional genomics and structural genomics. With nuclear magnetic resonance (NMR) spectroscopy as our primary tool, we examine the relationship between biomolecular structure, dynamics and function. NMR is uniquely sensitive to three-dimensional structural arrangements and the fluctuations that proteins and other biomolecules experience as they interact.
A primary focus in the lab is understanding how signalling and adhesion molecules interact with each other to direct the migration and activity of cells involved in immune responses. Many of these molecules are small soluble proteins, like cytokines and chemokines, which are ideal for study by NMR spectroscopy. Others, including selectins, extracellular matrix glycosaminoglycans (GAGs) and membrane-associated receptors are found on the surfaces of cells. All are involved in a vast array of binding reactions that are critical to immune system function. We use NMR and other biophysical and biochemical methods to study the detailed molecular interactions that direct signaling pathways within and between cells.
As a partner in the Center for Eukaryotic Structural Genomics, we are working to develop and apply streamlined methods for the acquisition and analysis of NMR data for the determination of three-dimensional protein structures. With a cryoprobe-equipped 600 MHz NMR spectrometer we can collect complete structural datasets in a small fraction of the time required with conventional instrumentation. When coupled with new software tools designed to automate most of the routine tasks in the data analysis pathway, we hope to contribute to a rapid maturation in the standard methodology for structural protein NMR.
Specific systems under investigation in the lab include:
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