Linda Columbus

Johnson MB, Ball LM, Daily KP, Martin JN, Columbus L and Criss AK. Opa+ Neisseria gonorrhoeae has reduced survival in human neutrophils via Src family kinase-mediated bacterial trafficking into mature phagolysosomes Cellular Microbiology.17:648-665 (2015)


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.

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Linda’s CV

Columbus L, Kroncke B.Solution NMR Structure Determination of Polytopic α-Helical Membrane Proteins: A Guide to Spin Label Paramagnetic Relaxation Enhancement Restraints. Methods in Enzymology 557: 329 – 348 (2015).

Straub AC, Mutchler S, Billaud M, Mykhaylo A, Palmer L, Le TH, Somlyo AV, Columbus L, Isakson BE. Hemoglobin α/eNOS coupling in endothelium is required for nitric oxide scavenging during vasoconstriction. Arteriosclerosis, Thrombosis, and Vascular Biology 34:2594 – 2600 (2014).

Isakson and Columbus receive Ivy Foundation Grant

The Ivy Foundation Biomedical Innovation Grants awarded Isakson and Columbus $80,000 in funding to develop novel anti-hypertensive therapeutics that target the hemoglobin alpha and eNOS interaction that they discovered.
Read more about other awards at UVA Today

Oliver RC, Lipfert J, Fox DA, Lo RH, Kim JJ, Doniach S, Columbus L. Tuning micelle dimensions and properties with binary surfactant mixtures
Langmuir. 30(44):13353-61 (2014)

Research from the Columbus Lab featured on cover of JACS

Opa proteins are outer membrane proteins in Neisseria meningitidis and Neisseria gonorrhoeae that have flexible extracelullar loops that interact with human receptors. This Opa-receptor interaction triggers the engulfment of the bacterium by human host cells. The cover shows several conformers of these loops extending from the Opa β-barrel which is embedded in a lipid bilayer.
View article.
And highlighted in the JACS Spotlight.

Fox DA , Larsson P, Lo RH, Kroncke BM, Kasson PM, and Columbus L

Structure of the Neisserial Outer Membrane Protein Opa60: Loop Flexibility Essential to Receptor Recognition and Bacterial Engulfment. Journal of the American Chemical Society. 136:9938 – 9946 (2014).

And highlighted in JACS Spotlight.

Lo RH, Kroncke BM, Solomon TL, and Columbus L. Mapping Membrane Protein Backbone Dynamics: A Comparison of Site-Directed Spin Labeling with NMR 15N-Relaxation Measurements
Biophysical Journal. 107: 1697-702 (2014).

Butcher JT, Johnson T, Beers J, Columbus L, Isakson BE.Hemoglobin α in the blood vessel wall. Free Radical Biology & Medicine 73C:136 – 142 (2014).

Baker LA, Chakraverty D, Columbus L, Feig AL, Jenks WS, Pilarz M, Stains M, Waterman R, and Wesemann J. Cottrell Scholars Collaborative New Faculty Workshop: Professional Development for New Chemistry Faculty and Initial Assessment of Its Efficacy Journal of Chemical Education 91: 1874-1881 (2014).

Ashton Brock and Ryan Lo present at the 58th Annual Meeting of the Biophysical Society

Linda, Ryan, and Ashton attended the 58th Annual Meeting of the Biophysical Society in San Francisco on February 15 – 19, 2014

Ryan presented a poster entitled “Structure, dynamics and receptor binding of Opa proteins” on Monday afternoons poster session.

Ashton presented a platform talk entitled “Influence of detergent properties on the solubilization and purification of membrane proteins” on Monday morning. Ashton also received a travel award from the Biophysical Society to attend the meeting.

Fox DA and Columbus L. Solution NMR resonance assignment strategies for β-barrel membrane proteins. Protein Science. 22: 1133–1140 (2013).

Anton BP et al. The COMBREX project: design, methodology, and initial results. PLoS Biol. 11:e1001638 (2013).

Linda receives the Virginia Outstanding Faculty Award

The Outstanding Faculty Awards are the Commonwealth’s highest honor for faculty at Virginia’s public and private colleges and universities. These awards recognize superior accomplishments in teaching, research, and public service.
See the articles in UVA Today and Cavalier Daily.

Columbus Lab Undergraduates Present at SURC 2014

On Thursday, January 30th, The Columbus Lab undergraduates drove to the University of Tennessee in Knoxville to attend the 46th Southeast Undergraduate Research Conference. Graduate students, Ashton Brock and Jennifer Martin and Linda joined them for the adventure.

Nana Bosomtwe presented a poster entitled Thermophilic Coupling Enzymes: Enabling Functional Studies at Physiological Temperatures and was the recipient of a travel award to the conference.

Elleansar Okwei presented a poster entitled Unraveling Aminotransferase Specificity: The activity of TM1131, TM1698, and TM1255 and received a Best Poster Presentation Award in the Biochemical division.

Tomihiro Ono presented a poster entitled Modulating Micelle Fluidity for Membrane Protein Structural Studies and received a Best Poster Presentation Award in the Physical division.

Sebastein Ortez presented a poster entitled Progress Towards Understanding OpaD Interactions with CEACAM1 and received a Best Poster Presentation Award in the Biochemical division.

Jessica Yoo presented a poster entitled Progress Towards Co-crystallization of the Broad Range Thermoplasma acidophilum nucleoside kinase (TaNK) with Substrates.

Kenwood BM, Weaver JL, Bajwa A, Poon IK, Byrne FL, Murrow BA, Calderone JA, Huang L, Divakaruni AS, Tomisg JL Okabe K, Lo RH, Coleman GC, Columbus L, Yan Z, Saucrman JJ, Smith JS, Homes JW, Lynch KR, Ravichandran KS, Uchiyama S, Santos WL, Rogers GW, Okusa MD, Bayliss DA, Hoehn KL. Identification of a novel mitochondrial uncoupler that does not depolarize the plasma membrane. Molecular Metabolism. 3:114 – 123 (2014).

Oliver RC, Lipfert J, Fox DA, Lo RH, Doniach S, Columbus L. Dependence of Micelle Size and Shape on Detergent Alkyl Chain Length and Head Group PLoS ONE. 8:e62488 (2013).

Fox and Columbus paper highlighted in Protein Science

Solution NMR resonance assignment strategies for β-barrel membrane proteins published this month in Protein Science was highlighted “In This Issue” by the journal.

Elkin SR, Kumar A, Price CW, Columbus L. A broad specificity nucleoside kinase from Thermoplasma acidophilum. Proteins. 81:568-82 (2013).

Straub AC, Lohman AW, Billaud M, Johnstone SR, Dwyer ST, Lee MY, Bortz PS, Best AK, Columbus L, Gaston B, Isakson BE. Endothelial cell expression of haemoglobin α regulates nitric oxide signalling. Nature. 491:473-7 (2012).

Linda receives UVA All-University Teaching Award

The UVA All-University Teaching Award is given for excellence in teaching with additional emphasis on research and service accomplishments. Nine awards were given each year to faculty through-out the University. Read more about this years awardees.

Kroncke B.M. and Columbus L. Identification and removal of nitroxide spin label contaminant: Impact on PRE studies of α-helical membrane proteins in detergent. Protein Science 21: 589–595 (2012).

Dewald AH, Hodges JC, Columbus L. Physical Determinants of β-Barrel Membrane Protein Folding in Lipid Vesicles. Biophysical Journal 100:2131 – 2140 (2011).

Ryan, Ryan, and Linda attend the FASEB Conference: Molecular Biophysics of Membranes in Snowmass, CO

This years FASEB Conference: Molecular Biophysics of Membranes was in Snowmass, CO and The University of Virgina was well represented with the Kasson, Tamm, Wiener, and Columbus laboratories represented. Ryan Oliver and Ryan Lo presented posters entitled “Modulating the physical properties of micelles using binary detergent mixtures for future membrane protein investigations” and “Effects of detergent, ionic strength, and temperature on the quality of β-barrel membrane protein NMR spectra”, respectively. Ryan Lo’s poster earned him an NSF Travel Award. The conference program was intense, but we managed some time for hiking.
Maroon Bells
Ryan Oliver and Linda
Ryan Lo and Ryan Oliver
Ryan O says the water is pretty cold.

Kroncke BM, Horanyi PS, and Columbus L. Structural origins of nitroxide side chain dynamics on membrane protein α-helical sites. Biochemistry 49:10045–10060 (2010)

Beuck C, Szymczyna BR, Kerkow DE, Carmel AB, Columbus L, Stanfield RL, Williamson JR. Structure of the GLD-1 homodimerization domain: insights into STAR protein-mediated translational regulation. Structure 18:377-89 (2010).

Columbus L, Lipfert J, Jambunathan K, Fox DA, Sim AYL, Doniach S, and Lesley SA. Mixing and Matching Detergents for Membrane Protein NMR Structure Determination J. Am. Chem. Soc. 131:7320–7326 (2009)

Columbus L, Nakamoto, RK, Cafiso, DS. Chapter in Wiley Encyclopedia of Chemical Biology (2008)

McCleverty C*, Columbus L*, Kreusch A, Lesley SA. Structure and ligand binding of the soluble domain of a Thermotoga maritima membrane protein of unknown function TM1634. Protein Science 17:869-77 (2008).

Lipfert J, Columbus L, Chu V, Doniach S. Analysis of small-angle X-ray scattering data of protein-detergent complexes with singular value decomposition. Journal of Applied Crystallography 40: s235-s239 (2007)

Lipfert J, Columbus L, Chu V, Lesley SA, Doniach S. Size and shape of detergent micelles determined by small-angle X-ray scattering. Journal of Physical Chemistry B 111: 12427-12438 (2007)

Columbus L, Lipfert J, Klock H, Millet I, Doniach S, Lesley SA. Expression, purification, and characterization of Thermotoga maritimamembrane proteins for structure determination. Protein Science 15: 961-975 (2006)

Kroncke and Columbus paper highlighted in Protein Science

Identification and removal of nitroxide spin label contaminant: Impact on PRE studies of α-helical membrane proteins in detergent published this month in Protein Science was highlighted “In This Issue” by the journal.

Columbus L, Peti W, Herrmann T, Etezady T, Wüthrich K. NMR structure determination of the conserved hypothetical protein TM1816 from Thermotoga maritima . Proteins: Structure, Function and Bioinformatics 60: 552-557 (2005)

Columbus L, Hubbell WL. Mapping backbone dynamics in solution with site-directed spin labeling: GCN4-58 bZip free and bound to DNA. Biochemistry 43: 7273-7287 (2004)

Liang ZC, Lou Y, Freed JH, Columbus L, Hubbell WL. A multifrequency electron spin resonance study of T4 lysozyme dynamics using the slowly relaxing local structure model Journal of Physical Chemistry B 108: 17649-17659 (2004)

Alison and Jackie’s paper #15 of the “Top 25 Hottest Articles” in Biophysical Journal

According to Science Direct, from April to June 2011

Physical Determinants of Beta-Barrel Membrane Protein Folding in Lipid Vesicles
Biophysical Journal, Volume 100, Issue 9, May 2011, Pages 2131-2140
Dewald, Alison H.; Hodges, Jacqueline C.; Columbus, L.

is 15th in the “Top 25 Hottest Articles” of Biophysical Journal.

Columbus L, Hubbell WL. A new spin on protein dynamics. Trends in Biochemical Sciences, 27: 288-295 (2002)

Columbus L, Kalai T, Jeko J, Hideg K, Hubbell WL. Molecular motion of spin labeled side chains in α-helices: Analysis by variation of side chain structure. Biochemistry 40: 3828-3846 (2001)

Gaponenko V, Howarth JW, Columbus L, Gasmi-Seabrook G, Yuan J, Hubbell WL, Rosevear PR. Protein global fold determination using site-directed spin and isotope labeling. Protein Science 9: 302-309 (2000)

Gross A, Columbus L, Hideg K, Altenbach C, Hubbell WL. Structure of the KcsA potassium channel from Streptomyces lividans: A site-directed spin labeling study of the second transmembrane segment. Biochemistry 38: 10324-10335 (1999)

Dan and Linda contribute to CIL’s Biomolecular NMR Product Catalog.

The new Cambridge Isotope Laboratories, Inc. Biomolecular NMR Product Catalog has pieces written by various NMR spectroscopists that utilize their isotopes. Dan adn Linda wrote a piece entitled “The role of deuterated detergents in NMR structure determination of membrane proteins” and is found on page 33.

Ryan, Ryan, and Linda attend the MidAtlantic BioSAXS Workshop

This April, Ryan Oliver, Ryan Lo, and Linda attended the Rigaku and UNC Chapel Hill sponsored MidAtlantic BioSAXS Workshop. The day-long workshop focused on the latest developments in BioSAXS technologies and applications.

Linda receives a 2010 Cottrell Scholar Award

The Cottrell Scholar Award (awarded by the Research Corporation for Science Advancement) supports the Columbus lab’s research on the structure and dynamics of bacterial outer membrane proteins and their interactions with host receptors. Specifically, the proposal focuses on the outer membrane opacity-associated (Opa) proteins from Neisseria, which induce engulfment of the bacterium in non-phagocytic cells by binding to host receptors. The results may provide insight into the pathogenesis of Neisseria, aid in the rational design of novel antibiotics, vaccine development, and targeting of liposome pharmaceutical carriers. The education component of the award allows Prof. Columbus to offer a UVA chemistry undergraduate course, which will introduce methods of drug discovery, entitled “From Lab Bench to Your Medicine Cabinet” in Fall 2011.

The Cottrell Scholar Awards are designed for institutions and faculty members who are committed to excel at both teaching and research. These awards ($75,000) enable recipients to implement their plans to become outstanding scientists and educators as well as tomorrow’s academic and scientific leaders. The awards also seek to reinforce faculty mentoring, communication, and a heightened appreciation for instruction in university science departments. This year their were 11 recipients of the award including another UVA faculty, Prof. Austen Lamacraft, in the UVA Physics Department.

The Cottrell Scholar Awards, instituted in 1994, are named in honor of Frederick Gardner Cottrell, scientist, inventor, and philanthropist. Dr. Cottrell founded Research Corporation for Science Advancement in 1912 and provided means for scientific research and experimentation at scholarly institutions. He not only contributed fundamentally and practically to scientific knowledge, but he dedicated his career to enlisting science in the service of society.

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