PI

Postdoctoral Research: The Scripps Research Institute
Advisors: Kurt Wuthrich and Scott Lesley
NMR and X-ray crystallography of Membrane proteins.

PhD: The University of California Los Angeles (2001)
Advisor: Wayne Hubbell
Mapping protein backbone dynamics with EPR Spectroscopy and site – directed spin labeling.

BA, high honors: Smith College (1996)
Advisor: David Bickar

Professor Columbus is interested in accelerating membrane protein techniques to investigate the structure and dynamics of membrane proteins involved in bacterial pathogenesis.

Linda Columbus’ CV

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Graduate Student

BS: Chemistry, Winthrop University (2011)
Ashton conducted undergraduate research with Dr. Takita Sumter on the regulation of High Mobility Group A1 proteins involved in colon cancer.

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Graduate Student

BS: Chemistry, Pennsylvania State University (2001)
M. Ed: Temple University, Educational Psychology (2006)
Alison conducted undergraduate research in the Guiltinan lab at the Penn State Biotechnology Institute, then taught chemistry and biology in Hershey, PA.

Alison’s research uses liposome (lipid vesicle) systems to investigate membrane proteins involved in bacterial pathogen – host interactions. Ultimately, her research aims to utilize the cellular hijacking mechanisms invented by pathogens (e.g. inducing phagocytosis, controlling cellular trafficking, and causing cell death) in the design of protein-decorated liposomes with novel characteristics desirable for drug delivery.

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Graduate Student

BS: Chemistry, University of Pittsburgh (2007)
Dan worked with Dr. David Pratt on rotationally resolved electronic spectroscopy and Dr. Megan Spence on solid state NMR of lipid bilayer systems.

Dan’s research aims to determine the binding mechanism of opacity associated (Opa) proteins located in the membrane of Neisseria bacteria. These proteins bind to human host receptors, CEACAM and heparin sulfate proteoglycan, and induce phagocytosis of the bacteria. He will be using various nuclear magnetic resonance (NMR) experiments and isotope labeling techniques to calculate a three dimension structure of OpaI reconstituted in detergent micelles. From there he will map out the interaction between CEACAM1 and Opa.

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Graduate Student

BS: Chemistry, University of Wisconsin-Madison (2007)
Brett worked with Dr. John Wright on ultrafast pulse recognition hardware and software design and implementation.

Brett aims to use quantitative information obtained from EPR spectra to improve structure and dynamics determination for α-helical membrane proteins. His work investigating the structure and dynamics of spin labels on a model membrane protein, LeuT, has provided a quantitative understanding of the EPR lineshape of detergent/lipid exposed nitroxides. Currently he is working with a model protein, TM0026, to assess the degree to which this understanding can improve paramagnetic relaxation enhancement (PRE) derived nuclear magnetic resonance (NMR) α-helical membrane protein structure determination.

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Graduate Student

BS: Chemistry with a Specialization in Biochemistry BA: Interdisciplinary Computer Science, University of Virginia (2011)
Chris conducted undergraduate research with Dr. Michael Shirts working on the automation of alchemical molecular design.

Chris’ current research involves developing computational workflows to augment static 3D structures with information about the ligand-binding properties of a protein of interest. Also I am interested in the development of tools which facilitate research based curricula.

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Co-advisor: Cameron Mura

Graduate Student

BA: Chemistry, Franklin and Marshall College (2009)
Ryan worked with Dr. Rick Moog on determining the Kamlet-Taft solvent parameters for various micellar environments.

Ryan’s research aims to investigate the effects of detergents on the structure and function of membrane proteins.

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Graduate Student

BS: Biology, Penn State Berks (2011)
Jen conducted undergraduate research with Dr. Ike Shibley looking at the effect of alcohol on protein expression levels in the brain of fetal chicks, and on redesigning the undergraduate Organic Chemistry courses.

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Graduate Student

MS: Chemistry, University of N. Carolina at Charlotte (2010)
BS: Chemistry, University of N. Carolina at Chapel Hill (2005)
Ryan worked with Dr. Joanna Krueger at UNC-Charlotte studying structures of protein complexes in solution using small-angle x-ray and neutron scattering.

Ryan is studying the physical determinants of membrane protein structure and dynamics. Detergent micelles are typically employed to solubilize and stabilize membrane proteins in a protein-detergent complex (PDC). Properties such as the matching of the hydrophobic dimensions between detergent micelle and membrane protein are key factors in stabilizing the protein’s fold, but a molecular understanding of protein-detergent interactions that stabilize a membrane protein fold is unknown. Ryan aims to investigate the geometry, structure, and dynamics of PDCs using biophysical methods such as NMR, EPR, and SAXS.

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Technician

BS: Chemistry with biochemistry focus, University of Virginia (2011)

Dan is working on characterizing proteins with known structure, but unknown function. Specifically, his work focuses on TM1385 which has been annotated as a glucose-6-phosphate isomerase; however, the function has yet to be investigated experimentally. Glucose-6-phosphate isomerases are a class of enzymes involved in the glycolysis and the gluconeogenisis pathways. They interconvert fructose-6-phosphate and glucose-6-phosphate. Kinetic studies and NMR studies (in collaboration with Golda Harris) are being conducted on both the wild type and the mutated forms of TM1385 to investigate the function and mechanism of TM1385.

Undergraduate Student – Fourth Year

Chemistry major with biochemistry focus

Tsiga’s research aims to further elucidate nixtroxide spin label dynamics at solvent exposed sites on α-helical membrane proteins. This project follows on the heels of a paper published by the lab (Biochemistry 49:10045–10060 (2010)) in which a model for nitroxide motion in an aliphatic environment was proposed. Tsiga will be extending this project to encompass a greater diversity of sites on α-helical membrane proteins using multiple nitroxide side chains, EPR linewidth simulations and X-ray crystallography on a model system α-helical membrane protein, LeuT.

Undergraduate Student – Fourth Year

Chemistry major with biochemistry focus
Distinguished Major Program

Jackie is studying the direct binding of Opa_HS (Opa₅₀) to heparansulfate proteoglycan receptors (HSPGs) using fluorescence techniques and heparin, a structural analog of HSPGs. She aims to confirm a selective interaction between this membrane protein and the host receptor and quantify the binding affinity. Further understanding of the intrinsic protein and receptor properties that determine this selectivity will enhance studies of the protein-triggered engulfment of the pathogens.

Undergraduate Student – Fourth Year

Chemistry major with biochemistry focus
Distinguished Major Program

Golda is studying the catalytic mechanism of TM1385, a phosphoglucose isomerase (PGI) enzyme from Thermotoga maritima. She aims to distinguish between two possible mechanisms of the enzyme-catalyzed isomerization; enediol intermediate or direct hydride shift through ¹H NMR and 2D ¹H-¹³C NMR spectroscopy. Mutational studies will also help to determine the roles of conserved active site residues in the catalytic mechanism. A better understanding of the mechanism used by the PGI from T. maritima will contribute to knowledge of the relationship between a particular PGI catalytic mechanism, the structure of the active site, and the overall fold of the enzyme.

Undergraduate Student – Fourth Year

Chemistry major with biochemistry focus
Distinguished Major Program

Sarah is working on characterizing the function of the protein 10640157 from the thermophilic bacterium Thermoplasma acidophilum. Based on the protein’s structure, it was putatively identified as a ribokinase. However, her research has shown that there is no evidence to support ribokinase activity. Instead, the protein 10640157 appears to use adenosine as substrate rather than ribose. She is currently investigating additional substrates and optimizing solution conditions to quantify the kinetic parameters of 10640157 activity.

Undergraduate Student – Fourth Year

Chemistry major with biochemistry focus

Elleansar is working on characterizing proteins with known structure, but unknown function.