William Laws

William R. Laws
Research Associate Professor

Email: bill.laws@umontana.edu

Phone: (406) 243-4107

Bill Laws came to UM in 2002 as part of the Core Spectroscopy Facility for Structural Biology. He obtained a B.S. in Chemistry from Purdue University in 1971 and a Ph.D. in Biochemistry from Johns Hopkins University in 1977. His thesis, under the guidance of Lenny Brand, employed time-resolved fluorescence to examine the use of excited-state proton transfer in studying biological systems. A post-doctoral position with Joe Shore in Detroit gave him experience with stopped-flow kinetics and enzyme-ligand interactions. As a visiting scientist and senior research associate with John Sutherland at Brookhaven National Laboratory, he designed and built a time-resolved fluorescence spectrometer for use at the National Synchrotron Light Source. He joined the faculty of Mount Sinai School of Medicine in 1985, where he taught biochemistry and physical biochemistry and continued studies towards the application of time-resolved fluorescence and other physical techniques to the study of biological systems.

 

Research Interests

We are interested in the role of structural changes, especially local dynamics, in the function of a biological macromolecule. These perturbations can result from the binding of small ligands or an interaction with another macromolecule. To investigate these motions, we employ ultrafast time-resolved fluorescence measurements; this technique provides us with picosecond/nanosecond resolution of events at specific sites in the macromolecule.

We are collaborating in employing this technology to a variety of systems. For example, we are using the intrinsic fluorescence from the amino acids phenylalanine and tyrosine to examine calcium-binding effects on calmodulin, an important regulatory protein of a number of biological processes. Another project is the use of the intrinsic fluorescence from the amino acid tryptophan to explore the roles of side chain motions on the function of the structural protein collagen. We are also involved with studies on the membrane-associated protein that starts blood coagulation, as well as enzyme-DNA complexes that achieve DNA repair.

Another aspect of our research is in the development of naturally-occurring (intrinsic) fluorescent molecules, new analogs of intrinsic fluorophores, as well as new extrinsic fluorescent probes by performing basic spectroscopic studies and then learning to apply them to a biological system. In addition, we work on the development of new/improved data acquisition, new mathematical approaches to data analysis, application of information from other biophysical techniques, and combining these experimental studies with theory, molecular modeling, and dynamic simulations. To help in these areas, we have recently installed a new laser system and unique sample chamber. However, we still want to extend our abilities of obtaining high quality time-resolved fluorescence data under different conditions, and to extract more information from the data, to help explore complicated systems.

Representative Publications

Vyleta, N.P., Coley, A.L., and Laws, W.R., (2004), Resolution of Molecular Dynamics by Time-Resolved Fluorescence Anisotropy: Verification of Two Kinetic Models, J. Phys. Chem. A 108:5156-5160 .

Simon-Lukasik, K.V., Persikov, A., Brodsky, B. Ramshaw, J.A., Laws, W.R., Ross, J.B.A., and Ludescher, R.D. (2003) Fluorescence Determination of Tryptophan Side Chain Accessibility and Dynamics in Triple-Helical Collagen-Like Peptides. Biophys. J. 84:501-508.

Feinstein, E., Deikus, G., Rusinova, E., Rachofsky, E.L., Ross, J.B.A., and Laws, W.R. (2003) Constrained Analysis of Fluorescence Anisotropy Decay: Application to Experimental Protein Dynamics. Biophys. J. 84:599-611.

Bialik, C.N., Wolf, B., Rachofsky, E.L., Ross, J.B.A, and Laws, W.R. (1998). Dynamics of Biomolecules: Assignment of Local Motions by Fluorescence Anisotropy Decay. Biophys. J. 75:2564-2573.

 

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