- Steel, Duncan

Duncan Steel

Professor of Biophysics Professor of Physics
Professor of Electrical Engineering & Computer Science

Ph.D. University of Michigan

Department of Physics
Office Address: 4235 Randall Laboratory; 3202 Chemistry
Phone: (734) 936-2143
Email: dst@umich.edu

Atomic, Molecular, Optical Physics

Steel Group Home Page

Professor Steel directs the Biomolecular Laser Spectroscopy Laboratory jointly with Professor Gafni from Biological Chemistry. Research using advanced laser spectroscopy techniques is designed to provide insight into fundamental questions associated with protein structure and dynamics and related issues including protein-protein and protein-DNA interactions and the general problem of biomolecular recognition. Experiments and designed to explore the nature of structural changes that occur as a result, for example, of aging, or other factors that lead to well known diseases such as Alzheimer's, cystic fibrosis and mad cow. Recent work includes their development of new laser techniques which enabled the group to discover that some proteins undergo structural changes following synthesis and biological activation in ways that were not detected by other methods. The groups primary laser based experimental approach is based on single molecule spectroscopy. Current work is now focusing specifically on understanding the origin of cellular toxicity in amyloidogenic diseases including Alzheimer's and type 2 diabetes. These diseases are characterized by protein deposits (plaques, etc) in the target tissue. The historical hypothesis has been that these deposits are the origin of the pathology. However, recent results suggest that the origin of cellular toxicity arises from the formation of small oligomers a long time before for the formation of the deposits. The small oligomers have been hypothesized to permeabilize the cellular membrane, leading to cell death. Studying the oligomers by conventional means is extremely challenging because they are highly heterogeneous, occur in small concentrations and have only a short life. Single molecule spectroscopy is perfect for the study of these structures. Our work is aimed at following the development of these oligomers and correlating the structure with the onset of cellular interactions and cell death.



Representative Publications
C.J. Fischer, J.A. Schauerte, D.G. Steel, A. Gafni, “The triplet-state lifetime of indole in aqueous and viscous environments: significance to the interpretation of room temperature phosphorescence in proteins,” J. Am. Chem. Soc. 124 pp 10359-10366 (2002). Jue Shi, Bruce A. Palfey, Joseph Dertouzos, Ari Gafni, and Duncan Steel, “Single molecule study of kinetics and mechanism of dihydroorotate dehydrogenase (DHOD),” Journal of the American Chemical Society 126, 6914-6922 (2004) Jeffrey R. Brender, Joe Dertouzos, David P. Ballou, Vincent Massey, Bruce A. Palfey, Barrie Entsch Ari Gafni, and Duncan Steel, “Conformational Dynamics of the Isoalloxazine Ring in Substrate-free PHBH: Single Molecule Studies”, JACS 27, pp18171-18178 (2005). Jue Shi, Ari Gafni, and Duncan Steel, “Simulated Data Sets for Single Molecule Kinetics: Some Limitations and Complications of Data Analysis,” European Biophysics Journal, in press (2006). Jue Shi, Joe Dertouzos, Ari Gafni, Duncan Steel, Bruce A. Palfey “Single-Molecule Kinetics Reveals New Signatures of Half-sites Reactivity in Dihydroorotate Dehydrogenase A Catalysis,” Proc. National Academy of Sciences, USA 103 pp5775-5780 (2006). Jue Shi, Gafni, A. and Steel, DG: Application of single molecule spectroscopy in studies of enzyme kinetics and mechanisms. Meth. Enzymol. 2006, in press.

Home
Search