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Education and Experience

Baylor University, Waco, TX, B.S. Chemistry, 1990
University of Iowa, Iowa City,  Ph.D., Biochemistry, 1995
W.M. Keck Center for Computational Biology, Postdoctoral Fellow, 1995-99
    Laboratories of B. Montgomery Pettit, Chemistry, University of Houston and 
    Kathleen Matthews, Biochemistry & Cell Biology, Rice University
Rice University, Biochemistry & Cell Biology Robert A. Welch Postdoctoral Fellow,
    2000-2002
Rice University, Biochemistry & Cell Biology, Research Scientist, 2002-2004
University of Kansas Medical Center, Assistant Professor, Biochemistry and Molecular
    Biology, 2004 - present

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Major Research Interests

Area of research emphasis:  Protein structure-function

 

A protein's molecular structure dictates its function. Frequently, proteins with similar structures perform similar functions. Data from the genome projects confirm that gross structural architectures can be used several times within a single organism. However, differences in fine structural details dictate specific and distinct functions critical to maintaining overall health. These details are not easy to decipher, as their identification is obscured by evolutionary “noise” in unimportant regions of the protein.  My approach to understanding the links between protein structure and function is to compare and contrast highly similar proteins.  My initial model system is the LacI/GalR family, whose proteins control transcriptional response in bacterial metabolic processes.  Specifically, I am interested in the information transmission that occurs through the protein structure between two distant binding sites required for the signaling process (allostery). Two projects, experimental and computational, are in progress:

EXPERIMENTAL: The general strategy is to interchange small regions of the highly related LacI/GalR proteins and use tools from biology and biochemistry to tease apart important details from irrelevant variations. Previous work predicts that allosteric communication will be destroyed in chimeric proteins, but additional mutations will restore intra-protein communication. Results will give insight to the required functional components of bacterial pathogens and can be applied to understanding distinct functions within other protein families.

COMPUTATIONAL: The core domains of LacI/GalR transcription control proteins are also structurally homologous to the periplasmic binding proteins and extracellular domains of some G-protein coupled receptors. All of these families are involved in signaling processes and utilize the same general strategy - bind a small molecule in a central cleft and propagate the message to another part of the protein. Differences between the proteins include: (1) The small molecule signal is different for each protein. (2) The signaling pathways through the protein structure as well as the final molecular location of the information is different both within and between the protein families. Targeted molecular dynamics (TMD) will be used to simulate motions in the proteins as the message is propagated from one binding site to another.  Data from related proteins will then be compared and contrasted to identify the range of signaling pathways supported by the common underlying protein fold.

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Databases of LacI Variants
Structural Effects of LacI Variants
Functional Effects of LacI Variants

Representative Publications

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