Research Team - NEW MEXICO CONSORTIUM

The Human Health and Agricultural Research Team scientists at the NMC are:

Gupta Goutam Alzheimers Team - New Mexico Consortium, Los Alamos, New Mexico

Goutam Gupta

Senior Research Scientist, New Mexico Consortium

https://newmexicoconsortium.org/goutam-gupta/

After obtaining his MS in Particle Physics, Dr. Gupta obtained his MS and PhD in Molecular Biophysics from the Indian Institute of Science, Bangalore, India. His PhD thesis on “Conformational Flexibility of DNA” garnered him a national young scientist award in 1983. After post-doctoral training in SUNY at Albany he began work at Los Alamos National Laboratory in 1990 in Theoretical Biology and Biophysics. Dr. Gupta’s group was the first to determine the high-resolution NMR structures of these DNA repeats and structure-function correlations to describe the mechanisms by which these repeats are abnormally expanded and cause aberrant expression of the associated genes and proteins leading to onset and progression of disease. He also determined the high-resolution NMR structures of different gp120-V3 loops and performed immunological assays to show how subtle changes in sequence lead to neutralizing escape mutants.

Dr. Gupta has combined structural biology, immunology, and genome research to determine the mechanisms of action of pathogenic bacteria and their virulence factors and toxins. This knowledge led to the development of pre-symptomatic diagnosis and therapy of human and plant bacteria. Currently, Dr. Gupta is also working on Alzheimer’s Disease to determine how the brain’s innate immune defense is compromised by amyloid formation and how it’s immunity can be re-engineered to prevent amyloid formation.

Selected Publications:

An engineered innate immune defense protects grapevines from Pierce disease. A. M. Dandekar, H. Gouran, A. M. Ibanez, S. L. Uratsu, C. B. Aguero, S. McFarland, Y. Borhani, P. A. Feldstein, G. Bruening, R. Nascimento, L. R. Goulart, P. E. Pardington, A. Chaudhary, M. Norvell, E. Civerolo, and G. Gupta. March 2012. Proceedings of the National Academy of Sciences. Volume 109, Number 10, 3721-3725.

A Dual-Purpose Protein Ligand for Effective Therapy and Sensitive Diagnosis of Anthrax. Momchilo Vuyisich, S. Gnanakaran, Julie A. Lovchik, C. Rick Lyons, Goutam Gupta. August 2008. The Protein Journal. 27:292.

Design of Chimeric Receptor Mimics with Different TCRVβ Isoforms: Type-specific Inhibition of Superantigen Pathogenesis. Hong-Geller E, Möllhoff M, Shiflett PR, Gupta G. 2004. J Biol Chem. 279: 5676–5684.

Hairpins are formed by the single DNA strands of the fragile X triplet repeats: structure and biological implications. Chen X, Mariappan SV, Catasti P, Ratliff R, Moyzis RK, Laayoun A, Smith SS, Bradbury EM, Gupta G. 1995. Proc Natl Acad Sci USA. 92:5199-5203.

Human immunodeficiency virus (HIV) antigens: structure and serology of multivalent human mucin MUC1-HIV V3 chimeric proteins. Fontenot, J. D., J. M. Gatewood, S. V. Mariappan, C. P. Pau, B. S. Parekh, J. R. George, and G. Gupta. 1995. Proc. Natl. Acad. Sci. USA 92:315-319.

Local and global structural properties of the HIV-MN V3 loop. P. Catasti, J.D. Fontenot, E.M. Bradbury, G. Gupta. 1995. J. Biol. Chem. 270. pp. 2224-2232.

Loss of a neutralizing epitope by a spontaneous point mutation in the V3 loop of HIV-1 isolated from an infected laboratory worker. Veronese FM, Reitz MS, Gupta G, Robert-Guroff M, Boyer-Thompson C, Louie A, Gallo RC, Lusso P. 1993. J Biol Chem. 268: 25894–25901.

Conformational flexibility of DNA: polymorphism and handedness. G Gupta, M Bansal, V Sasisekharan. 1980. Proceedings of the National Academy of Sciences. 77 (11), 6486-6490.

Patents:

Biomarkers for the pre-symptomatic diagnosis of huanglongbing (hlb) in citrus and use thereof. Goutam Gupta, Eddie Wayne Stover, Paige Pardington Melinda Wren. US Patent 20170145478 A1. May 25, 2017.

Compositions and methods for the treatment of Pierce’s Disease. Goutam Gupta. US Patent 20090158470 A1. June 18, 2009.

Structure-based receptor MIMICS targeted against bacterial superantigen toxins. Goutam Gupta, Elizabeth Hong-Geller, Patrick Shiflett, Nancy Lehnert. US Patent 20050260222 A1. November 24, 2005.

Thomas Terwilliger Alzheimers Team - New Mexico Consortium, Los Alamos, New Mexico

Thomas C. Terwilliger

B Division, LANL, NMC Research Scientist

https://solve.lanl.gov/terwilliger

Dr. Terwilliger’s research has focused on the development of algorithms for determination of macromolecular structures and determining structures of proteins from pathogenic organisms. He is a member of the Phenix software team, leading the development of tools for improving the images of protein structures determined by X-ray crystallography and cryo-electron microscopy and tools for constructing atomic models of macromolecules from these images. He was the inventor of the “SOLVE” software that allowed the first fully automatic interpretation of macromolecular X-ray diffraction data. He was the leader of two NIH Protein Structure Initiative Centers and is the author of over 200 publications.

Selected Publications

Can I solve my structure by SAD phasing? Anomalous signal in SAD phasing. Terwilliger, T. C., Bunkóczi, G., Hung, L.-W., Zwart, P. H., Smith, J. L., Akey, D. L., Adams, P.D. 2016. Acta Cryst. D72, 346-358.

Outcome of the First wwPDB/CCDC/D3R Ligand Validation Workshop. Adams, P.D., et al. 2016. Structure 24, 502-408.

A suite of engineered GFP molecules for oligomeric scaffolding. Leibly, D. J., Arbing, M. A., Pashkov, I., DeVore, N., Waldo, G.S., Terwilliger, T.C., Yeates, T.O. 2015. Structure 23, 1754-1768.

X-ray structure determination using low-resolution electron microscopy maps for molecular replacement. Jackson, R. N., Terwilliger, T. C., Read, R. J., Wiedenheft, B. 2015. Nature Protocols 10, 1275-1284.

Macromolecular X-ray structure determination using weak single-wavelength anomalous data. Bunkóczi, G., McCoy, A.J., Echols, N., Grosse-Kunstleve, R.W., Adams, P.D., Holton, J. M., Read, R.J., Terwilliger, T.C. 2015. Nature Methods 12, 127-130.

Subfamily-specific adaptations in the structures of two penicillin-binding proteins from Mycobacterium tuberculosis. Prigozhin, D.M., Krieger, I.V., Huizar, J.P., Mavrici, D., Waldo, G.S., Hung, L.W., Sacchettini, J.C., Terwilliger, T.C., Alber, T. 2014. PLos ONE 9, e116249.

Crystal structure of the CRISPR RNA-guided surveillance complex from Escherichia coli. Jackson, R.N., Golden, S.M., van Erp, P.B.G., Carger, J., Westra, E.R., Brouns, S.J.J., van der Oost, J., Terwilliger, T.C., Read, R.J., Widenheft, B. 2014. Science 345, 1473-1479.

Continuous mutual improvement of macromolecular structure models in the PDB and of X-ray crystallographic software: the dual role of deposited experimental data. Terwilliger, T.C., Bricogne, G. 2014. Acta Cryst. D70, 2533-2543.

Crystal structure of AcrB complexed with linezolid at 3.5 Å resolution. Hung, L.-W., Kim, H.-B., Murakami, S., Gupta, G., Kim, C.-Y., Terwilliger, T.C. 2013. J. Struct. Func. Genomics 14, 71-75.

Improved Crystallographic Structures Using Extensive Combinatorial Refinement. Nwachukwu, J. C., Southern, M. R., Kiefer, J. R., Afonine, P. V., Adams, P. D., Terwilliger, T. C., Nettles, K. W. 2013. Structure, 21, 1923-1930.

Improved low-resolution crystallographic refinement with Phenix and Rosetta. DiMaio, F., Echols, N., Headd, J. J., Terwilliger, T. C., Adams, P. D., & Baker, D. (2013). Nature Methods 10, 1102-1104.

Crystal structure of Bacillus subtilis GabR, an autorepressor and transcriptional activator of gabT. Edayathumangalam, R., Wu, R., Garcia, R., Wang, Y., Wang, W., Kreinbring, C. A., Bach, A., Liao, J., Stone, T., Terwilliger, T.C., Hoang, Q.Q., Belitsky, B.R., Petsko, G.A., Liu, D. (2013). Proceedings of the National Academy of Sciences, 110, 17820-17825.

Improving molecular replacement by density and energy guided protein structure optimization DiMaio, F., Terwilliger, T.C., Read, R.J., Wlodawer, A., Oberdorfer, G., Wagner, U., Valkov, E., Alon, A., Fass, D., Axelrod, H.L., Das, D., Vorobiev, S.M., Iwai, H., Pokkuluri, P.R., D. Baker (2011). Nature 473, 540-543.

PHENIX: a comprehensive Python-based system for macromolecular structure solution. Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L.-W., Kapral, G. J., Grosse-Kunstleve, R. W., McCoy, A. J., Moriarty, N. W., Oeffner, R., Read, R. J., Richardson, D. C., Richardson, J. S., Terwilliger, T. C., Zwart, P. H. 2010. Acta Cryst. D66, 213-221.

New Molecular Reporters for Rapid Protein Folding Assays. Cabantous S, Rogers Y, Terwilliger T, Waldo GS (2008). PLoS ONE 3(6): 1-10 (e2387).

Protein production and purification. Structural Genomics Consortium et al.,. Nature Methods. 2008, 135-46.

Functional linkages can reveal protein complexes for structure determination. Kim, S.M., Bowers, P.M., Pal, .D, Strong, M., Terwilliger, T.C., Kaufmann, M., Eisenberg, .D. (2007). Structure 15, 1079-1089.

Is one solution good enough? Furnham, N., Blundell, T. L., DePristo, M. A., Terwilliger, T.C. (2006). Nature Structural & Molecular Biology 13, 184 – 185.

Engineering and characterization of a superfolder green fluorescent protein. Pédelacq, J.-D., Cabantous, S., Tran, T., Terwilliger, T.C., Waldo, G. S. (2006). Nature Biotechnology, 24, 79-88.

Structure of pyrR (Rv1379) from Mycobacterium tuberculosis: a persistence gene and protein drug target. Kantardjieff KA, Vasquez C, Castro P, Warfel NM, Rho BS, Lekin T, Kim CY, Segelke BW, Terwilliger TC, Rupp B. 2005. Acta Cryst D 61, 355-364.

Protein tagging and detection with engineered self-assembling fragments of green fluorescent protein. Cabantous, S., Terwilliger, T. C., Waldo, G. S. (2005). Nature Biotechnology 23, 102-107.

Structures and technology for biologists.Terwilliger, T. C. 2004. Nature Structural and Molecular Biology 11, 296-297.

The Crystal Structure of the First Enzyme in the Pantothenate Biosynthetic Pathway, Ketopantoate Hydroxymethyltransferase, from M. tuberculosis. Chaudhuri, B. N., Sawaya, M. R., Kim, C.-Y., Waldo, G. S., Park, M. S., Terwilliger, T. C. & Todd O. Yeates, T. O. 2003. Structure, 11, 753-764

Engineering soluble proteins for structural genomics. Pédelacq, J.-D., Piltch, E., Liong, E. E., Berendzen, J., Kim, C.-Y., Rho, B.-S., Park, M. S., Terwilliger, T. C. & Waldo, G. S (2012). Nature Biotechnology, 20, 927-932.

Structural Genomics in North America. Terwilliger, T. C. (2000). Nature Structural Biology 7, 935-939.

Maximum-likelihood density modification. Terwilliger, T. C. (2000). Acta Crystallographica, D55, 965-972.

Automated MAD and MIR structure solution. Terwilliger, T. C. and Berendzen, J. (1999). Acta Crystallographica, D55, 849-861.

Rapid protein-folding assay using green fluorescent protein. Waldo, G., Standish, B. M., Berendzen, J. & Terwilliger, T. C. (1999) Nature Biotechnology 17, 691-695.

Structure Of Translation Initiation-Factor 5a From Pyrobaculum-Aerophilum At 1.75 Angstrom Resolution. Peat T.S., Newman J, Waldo G.S, Berendzen J., Terwilliger T.C. (1998) Structure 6, 1207-1214.

Potential use of additivity of mutational effects in simplifying protein engineering. Skinner, M. M. and Terwilliger, T. C. (1996) Proc. Natl. Acad. Sci. USA 93, 10753-10757.

Structure of the gene V protein of bacteriophage f1 determined by multiwavelength X- ray diffraction on the selenomethionyl protein. Skinner, M. M., Zhang, H., Leschnitzer, D. H. , Guan, Y., Bellamy, H., Sweet, R. M., Gray, C. W., Konings, R. N. H., Wang, A. H.-J., and T. C. Terwilliger (1994). Proc. Natl. Acad. Sci. USA 91, 2071-2075.

Engineering multiple properties of a protein by combinatorial mutagenesis. Sandberg, W. S and T. C. Terwilliger (1993). Proc. Natl. Acad. Sci. USA 90, 8367-8371.

Energetics of repacking a protein interior. Sandberg, W. S. and T. C. Terwilliger (1991). Proc. Natl. Acad. Sci. USA 88, 1706-1710.

Influence of interior packing and hydrophobicity on the stability of a protein. Sandberg, W. S. and T. C. Terwilliger (1989). Science 245, 54-57.

Surface structure recognized for covalent modification of the aspartate receptor in chemotaxis. Terwilliger, T. C., Wang, J. Y. and D. E. Koshland, Jr. (1986). Proc. Natl. Acad. Sci. USA 83, 6707-6710.

The hydrophobic moment detects periodicity in protein hydrophobicity. Eisenberg, D., Weiss, R. M., and T. C. Terwilliger. (1984). Proc. Natl. Acad. Sci. USA 81, 140-144.

The helical hydrophobic moment: a measure of the amphiphilicity of a helix. Eisenberg, D., Weiss, R. M., and T. C. Terwilliger (1982). Nature 299, 371-374.