---

In my laboratory we employ a multifaceted approach to research. We study the three-dimensional structures of proteins in detail and use this information to construct hypotheses about interactions that may be crucial for a protein's stability or function. We then test these hypotheses by using molecular biology techniques to create mutant proteins with amino acid substitutions at positions we believe to be important. The in vitro properties of these mutant proteins are assessed using biophysical methods such as circular dichroism spectroscopy, tryptophan fluorescence spectroscopy, and nuclear magnetic resonance spectroscopy.In this way, can determine exactly how particular amino acid substitutions affect the protein's activity and thermodynamic stability.We also assess the ability of these mutant proteins to carry out their normal functions inside the cell. All of this research is aided by our studies in the area of bioinformatics. These investigations involve the construction and careful analysis of large and comprehensive sequence alignments. We are developing new methods to extract useful information from this rich source of data, and we have designed a number of successful experiments based on conclusions drawn from our bioinformatics studies.