protein engineering

Summary

Summary: Procedures by which protein structure and function are changed or created in vitro by altering existing or synthesizing new structural genes that direct the synthesis of proteins with sought-after properties. Such procedures may include the design of MOLECULAR MODELS of proteins using COMPUTER GRAPHICS or other molecular modeling techniques; site-specific mutagenesis (MUTAGENESIS, SITE-SPECIFIC) of existing genes; and DIRECTED MOLECULAR EVOLUTION techniques to create new genes.

Top Publications

  1. pmc Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter
    L M Guzman
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Bacteriol 177:4121-30. 1995
  2. ncbi The discovery of zinc fingers and their applications in gene regulation and genome manipulation
    Aaron Klug
    MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom
    Annu Rev Biochem 79:213-31. 2010
  3. pmc A novel TALE nuclease scaffold enables high genome editing activity in combination with low toxicity
    Claudio Mussolino
    Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany
    Nucleic Acids Res 39:9283-93. 2011
  4. ncbi Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein
    Nathan C Shaner
    Nat Biotechnol 22:1567-72. 2004
  5. ncbi Engineering and characterization of a superfolder green fluorescent protein
    Jean Denis Pédelacq
    Bioscience Division, MS M888, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
    Nat Biotechnol 24:79-88. 2006
  6. pmc Modularly assembled designer TAL effector nucleases for targeted gene knockout and gene replacement in eukaryotes
    Ting Li
    Department of Genetics, Development and Cell Biology, Laurence H Baker Center for Bioinformatics and Biological Statistics, University of Nebraska, Lincoln, NE 68588, USA
    Nucleic Acids Res 39:6315-25. 2011
  7. pmc Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA)
    Jeffry D Sander
    Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA
    Nat Methods 8:67-9. 2011
  8. pmc Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases
    Yannick Doyon
    Sangamo BioSciences, Inc, Pt Richmond Tech Center, 501 Canal Blvd, Suite A100, Richmond, California 94804, USA
    Nat Biotechnol 26:702-8. 2008
  9. pmc Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases
    Xiangdong Meng
    Program in Gene Function and Expression, University of Massachusetts Medical School, Lazare Research Building, 6th Floor, 364 Plantation St, Worcester, Massachusetts 01605, USA
    Nat Biotechnol 26:695-701. 2008
  10. pmc Engineered zinc finger nickases induce homology-directed repair with reduced mutagenic effects
    Cherie L Ramirez
    Molecular Pathology Unit, Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Nucleic Acids Res 40:5560-8. 2012

Research Grants

Detail Information

Publications304 found, 100 shown here

  1. pmc Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter
    L M Guzman
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Bacteriol 177:4121-30. 1995
    ..We have exploited the tight regulation of the PBAD promoter to study the phenotypes of null mutations of essential genes and explored the use of pBAD vectors as an expression system...
  2. ncbi The discovery of zinc fingers and their applications in gene regulation and genome manipulation
    Aaron Klug
    MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom
    Annu Rev Biochem 79:213-31. 2010
    ..g., from nucleases or integrases, to form chimeric proteins, genomes could be manipulated or modified. Several applications of such engineered zinc finger proteins are described here, including some of therapeutic importance...
  3. pmc A novel TALE nuclease scaffold enables high genome editing activity in combination with low toxicity
    Claudio Mussolino
    Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany
    Nucleic Acids Res 39:9283-93. 2011
    ..The combination of high nuclease activity with reduced cytotoxicity and the simple design process marks TALENs as a key technology platform for targeted modifications of complex genomes...
  4. ncbi Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein
    Nathan C Shaner
    Nat Biotechnol 22:1567-72. 2004
    ..Three monomers with distinguishable hues from yellow-orange to red-orange have higher quantum efficiencies...
  5. ncbi Engineering and characterization of a superfolder green fluorescent protein
    Jean Denis Pédelacq
    Bioscience Division, MS M888, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
    Nat Biotechnol 24:79-88. 2006
    ..X-ray crystallographic structural analyses helped explain the enhanced folding of superfolder GFP relative to folding reporter GFP...
  6. pmc Modularly assembled designer TAL effector nucleases for targeted gene knockout and gene replacement in eukaryotes
    Ting Li
    Department of Genetics, Development and Cell Biology, Laurence H Baker Center for Bioinformatics and Biological Statistics, University of Nebraska, Lincoln, NE 68588, USA
    Nucleic Acids Res 39:6315-25. 2011
    ....
  7. pmc Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA)
    Jeffry D Sander
    Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA
    Nat Methods 8:67-9. 2011
    ..The simplicity and efficacy of CoDA will enable broad adoption of ZFN technology and make possible large-scale projects focused on multigene pathways or genome-wide alterations...
  8. pmc Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases
    Yannick Doyon
    Sangamo BioSciences, Inc, Pt Richmond Tech Center, 501 Canal Blvd, Suite A100, Richmond, California 94804, USA
    Nat Biotechnol 26:702-8. 2008
    ..The frequency and precision of gene-disruption events observed suggest that this approach should be applicable to any loci in zebrafish or in other organisms that allow mRNA delivery into the fertilized egg...
  9. pmc Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases
    Xiangdong Meng
    Program in Gene Function and Expression, University of Massachusetts Medical School, Lazare Research Building, 6th Floor, 364 Plantation St, Worcester, Massachusetts 01605, USA
    Nat Biotechnol 26:695-701. 2008
    ..The use of engineered ZFNs to introduce heritable mutations into a genome obviates the need for embryonic stem cell lines and should be applicable to most animal species for which early-stage embryos are easily accessible...
  10. pmc Engineered zinc finger nickases induce homology-directed repair with reduced mutagenic effects
    Cherie L Ramirez
    Molecular Pathology Unit, Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Nucleic Acids Res 40:5560-8. 2012
    ..ZFNickases thus provide a promising means for inducing HDR-mediated gene modifications while reducing unwanted mutagenesis caused by error-prone NHEJ...
  11. ncbi Strategies and challenges for the next generation of therapeutic antibodies
    Alain Beck
    Centre d Immunologie Pierre Fabre CIPF, 5 Avenue Napoleon III, F74160, Saint Julien en Genevois, France
    Nat Rev Immunol 10:345-52. 2010
    ..Here, we discuss strategies to select the best therapeutic antigen targets, to optimize the structure of IgG antibodies and to design related or new structures with additional functions...
  12. ncbi Recombinant protein expression in Escherichia coli
    F Baneyx
    Department of Chemical Engineering University of Washington Box 351750, Seattle, WA 98195, USA
    Curr Opin Biotechnol 10:411-21. 1999
    ..coli, together with serendipitous discoveries and the availability of improved genetic tools are making this bacterium more valuable than ever for the expression of complex eukaryotic proteins...
  13. ncbi Adding new chemistries to the genetic code
    Chang C Liu
    The Scripps Research Institute, La Jolla, California 92037, USA
    Annu Rev Biochem 79:413-44. 2010
    ....
  14. ncbi Design of a novel globular protein fold with atomic-level accuracy
    Brian Kuhlman
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Science 302:1364-8. 2003
    ..2 angstroms) to the design model. The ability to design a new protein fold makes possible the exploration of the large regions of the protein universe not yet observed in nature...
  15. pmc Homing endonucleases: from microbial genetic invaders to reagents for targeted DNA modification
    Barry L Stoddard
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, A3 025, Seattle, WA 98109, USA
    Structure 19:7-15. 2011
    ..Engineered homing endonucleases proteins are now being used to generate targeted genomic modifications for a variety of biotech and medical applications...
  16. pmc De novo-engineered transcription activator-like effector (TALE) hybrid nuclease with novel DNA binding specificity creates double-strand breaks
    Magdy M Mahfouz
    Center for Plant Stress Genomics and Technology, King Abdullah University of Science and Technology, Thuwal 23955 6900, Kingdom of Saudi Arabia
    Proc Natl Acad Sci U S A 108:2623-8. 2011
    ..Taken together, our data show the feasibility of engineering TALE-based hybrid nucleases capable of generating site-specific DSBs and the great potential for site-specific genome modification in plants and eukaryotes in general...
  17. ncbi Advanced genetic strategies for recombinant protein expression in Escherichia coli
    Hans Peter Sørensen
    Laboratory of BioDesign, Department of Molecular Biology, Aarhus University, Gustav Wieds Vej 10 C, DK 8000 Aarhus C, Denmark
    J Biotechnol 115:113-28. 2005
    ..The macromolecular background for a variety of obstacles and genetic state-of-the-art solutions are presented...
  18. ncbi Expression of heterologous proteins in Pichia pastoris: a useful experimental tool in protein engineering and production
    Rachel Daly
    ARC Special Research Centre for Green Chemistry, Monash University, Building 23, Wellington Road, Clayton, Victoria 3800, Australia
    J Mol Recognit 18:119-38. 2005
    ..Procedures to prevent glycosylation through manipulation of cell culture conditions or via enzymatic and site-directed mutagenesis methods are also discussed...
  19. pmc Targeted gene addition to a predetermined site in the human genome using a ZFN-based nicking enzyme
    Jianbin Wang
    Sangamo Biosciences Inc, Richmond, California 94804, USA
    Genome Res 22:1316-26. 2012
    ..Moreover, the potential for a SSB to direct repair pathway choice (i.e., HDR but not NHEJ) may prove advantageous for certain therapeutic applications such as the targeted correction of human disease-causing mutations...
  20. pmc High-frequency modification of plant genes using engineered zinc-finger nucleases
    Jeffrey A Townsend
    Department of Genetics, Development and Cell Biology, Iowa State University, Ames, Iowa 50011, USA
    Nature 459:442-5. 2009
    ..More than 40% of recombinant plants had modifications in multiple SuR alleles. The observed high frequency of gene targeting indicates that it is now possible to efficiently make targeted sequence changes in endogenous plant genes...
  21. pmc ZiFiT (Zinc Finger Targeter): an updated zinc finger engineering tool
    Jeffry D Sander
    Molecular Pathology Unit, Center for Cancer Research, and Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Nucleic Acids Res 38:W462-8. 2010
    ..ZiFiT is freely available on the web without registration at http://bindr.gdcb.iastate.edu/ZiFiT/...
  22. pmc Mammalian expression of infrared fluorescent proteins engineered from a bacterial phytochrome
    Xiaokun Shu
    Howard Hughes Medical Institute, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0647, USA
    Science 324:804-7. 2009
    ..Because their wavelengths penetrate tissue well, IFPs are suitable for whole-body imaging. The IFPs developed here provide a scaffold for further engineering...
  23. pmc Engineering domain fusion chimeras from I-OnuI family LAGLIDADG homing endonucleases
    Sarah Baxter
    Department of Immunology, University of Washington, Seattle, WA 98195, USA
    Nucleic Acids Res 40:7985-8000. 2012
    ..This method will be useful for creating large numbers of chimeric LHEs for genome engineering applications...
  24. pmc I-Mutant2.0: predicting stability changes upon mutation from the protein sequence or structure
    Emidio Capriotti
    Laboratory of Biocomputing, CIRB Department of Biology, University of Bologna via Irnerio 42, 40126 Bologna, Italy
    Nucleic Acids Res 33:W306-10. 2005
    ..0 as a unique and valuable helper for protein design, even when the protein structure is not yet known with atomic resolution. Availability: http://gpcr.biocomp.unibo.it/cgi/predictors/I-Mutant2.0/I-Mutant2.0.cgi...
  25. pmc Assembly of custom TALE-type DNA binding domains by modular cloning
    Robert Morbitzer
    Institute of Biology, Genetics, University of Munich LMU, 82152 Martinsried and Institute of Biology, Martin Luther University, 06099 Halle, Germany
    Nucleic Acids Res 39:5790-9. 2011
    ..This approach enables the rapid and flexible production of dTALEs for gene regulation and genome editing in routine and high-throughput applications...
  26. pmc Assembly of designer TAL effectors by Golden Gate cloning
    Ernst Weber
    Icon Genetics GmbH, Halle Saale, Germany
    PLoS ONE 6:e19722. 2011
    ..Applying this strategy, we assembled designer TALEs with new target specificities and tested their function in vivo...
  27. pmc Ultrafast protein splicing is common among cyanobacterial split inteins: implications for protein engineering
    Neel H Shah
    Department of Chemistry, Princeton University, 325 Frick Chemistry Laboratory, Princeton, New Jersey 08544, USA
    J Am Chem Soc 134:11338-41. 2012
    ..This comprehensive survey of split inteins provides indispensable information for the development and improvement of intein-based tools for chemical biology...
  28. pmc Computational reprogramming of homing endonuclease specificity at multiple adjacent base pairs
    Justin Ashworth
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Nucleic Acids Res 38:5601-8. 2010
    ....
  29. pmc High frequency targeted mutagenesis in Arabidopsis thaliana using zinc finger nucleases
    Feng Zhang
    Department of Genetics, Cell Biology, and Development and Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA
    Proc Natl Acad Sci U S A 107:12028-33. 2010
    ..Taken together, our results suggest that it should now be possible to obtain mutations in any Arabidopsis target gene regardless of its mutant phenotype...
  30. pmc Scaffolds: interaction platforms for cellular signalling circuits
    András Zeke
    Department of Biochemistry, Eotvos Lorand University, Pazmany Peter setany 1 C, H 1117 Budapest, Hungary
    Trends Cell Biol 19:364-74. 2009
    ..In this review, we discuss the role of scaffold proteins as efficient tools for assembling intracellular signalling complexes, both natural and artificial...
  31. pmc An inducible translocation strategy to rapidly activate and inhibit small GTPase signaling pathways
    Takanari Inoue
    Stanford University, Department of Molecular Pharmacology, Clark Center, 318 Campus Drive, Stanford, California 94305 5439, USA
    Nat Methods 2:415-8. 2005
    ..As signaling processes often occur within minutes, such rapid perturbations provide a powerful tool to investigate the role, selectivity and timing of Rho GTPase-mediated signaling processes...
  32. pmc Tapping natural reservoirs of homing endonucleases for targeted gene modification
    Ryo Takeuchi
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North A3 025, Seattle, WA 98109, USA
    Proc Natl Acad Sci U S A 108:13077-82. 2011
    ..The ubiquitous presence and diversity of LHEs described in this study may facilitate the creation of many tailored nucleases for genome editing...
  33. pmc Structure-guided reprogramming of serine recombinase DNA sequence specificity
    Thomas Gaj
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 108:498-503. 2011
    ..These results demonstrate that unique resolvase and invertase derivatives can be developed to site-specifically modify the human genome in the context of zinc-finger recombinase fusion proteins...
  34. ncbi Structure of a 16-nm cage designed by using protein oligomers
    Yen Ting Lai
    University of California Los Angeles Biomedical Engineering Interdepartmental Program, Los Angeles, CA 90095, USA
    Science 336:1129. 2012
    ..The strategy of fusing together oligomeric protein domains can be generalized to produce other kinds of cages or extended materials...
  35. ncbi Recombinant protein expression and purification: a comprehensive review of affinity tags and microbial applications
    Carissa L Young
    Department of Chemical Engineering, University of Delaware, Newark, DE, USA
    Biotechnol J 7:620-34. 2012
    ..This review serves as an excellent literature reference for those working on protein fusion tags...
  36. pmc Use of combinatorial genetic libraries to humanize N-linked glycosylation in the yeast Pichia pastoris
    Byung Kwon Choi
    Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA
    Proc Natl Acad Sci U S A 100:5022-7. 2003
    ..Here we report a yeast able to synthesize hybrid glycans in high yield and open the door for engineering yeast to perform complex human-like glycosylation...
  37. pmc Requirements of the engineered leader peptide of nisin for inducing modification, export, and cleavage
    Annechien Plat
    BiOMaDe Technology Foundation, Nijenborgh 4, 9747 AG Groningen, Netherlands
    Appl Environ Microbiol 77:604-11. 2011
    ..Reducing the leader peptide to MSTKDFNLDLR led to 3- or 4-fold dehydration. Taken together, the FNLD box is crucial for inducing posttranslational modifications...
  38. ncbi Engineered protein scaffolds as next-generation antibody therapeutics
    Michaela Gebauer
    Lehrstuhl fur Biologische Chemie, Technische Universitat Munchen, Freising Weihenstephan, Germany
    Curr Opin Chem Biol 13:245-55. 2009
    ....
  39. ncbi A photoactivatable GFP for selective photolabeling of proteins and cells
    George H Patterson
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Science 297:1873-7. 2002
    ..Here, we use the photoactivatable GFP both as a free protein to measure protein diffusion across the nuclear envelope and as a chimera with a lysosomal membrane protein to demonstrate rapid interlysosomal membrane exchange...
  40. ncbi Introduction to current and future protein therapeutics: a protein engineering perspective
    Paul J Carter
    Department of Antibody Engineering, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080 4990, USA
    Exp Cell Res 317:1261-9. 2011
    Protein therapeutics and its enabling sister discipline, protein engineering, have emerged since the early 1980s. The first protein therapeutics were recombinant versions of natural proteins...
  41. ncbi Codon bias and heterologous protein expression
    Claes Gustafsson
    DNA 2 0, 1455 Adams Drive, Menlo Park, CA 94025, USA
    Trends Biotechnol 22:346-53. 2004
    ..Redesign strategies are discussed here, including modification of translation initiation regions, alteration of mRNA structural elements and use of different codon biases...
  42. pmc Beyond directed evolution--semi-rational protein engineering and design
    Stefan Lutz
    Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA 30322, USA
    Curr Opin Biotechnol 21:734-43. 2010
    Over the past two decades, directed evolution has transformed the field of protein engineering. The advances in understanding protein structure and function, in no insignificant part a result of directed evolution studies, are ..
  43. ncbi Antibody recycling by engineered pH-dependent antigen binding improves the duration of antigen neutralization
    Tomoyuki Igawa
    Chugai Pharmaceutical Co Ltd, Fuji Gotemba Research Laboratories, Shizuoka, Japan
    Nat Biotechnol 28:1203-7. 2010
    ..Engineering pH dependency into the interactions of therapeutic antibodies with their targets may enable them to be delivered less frequently or at lower doses...
  44. pmc Targeted plasmid integration into the human genome by an engineered zinc-finger recombinase
    Charles A Gersbach
    The Skaggs Institute for Chemical Biology, Department of Molecular Biology, CA, USA
    Nucleic Acids Res 39:7868-78. 2011
    ..This work demonstrates the potential for broad applicability of the ZFR technology in genome engineering, synthetic biology and gene therapy...
  45. pmc Creating highly specific nucleases by fusion of active restriction endonucleases and catalytically inactive homing endonucleases
    Ines Fonfara
    Institut fur Biochemie, Justus Liebig Universitat Giessen, Heinrich Buff Ring 58, D 35392, Giessen, Germany
    Nucleic Acids Res 40:847-60. 2012
    ....
  46. pmc Oligomerized pool engineering (OPEN): an 'open-source' protocol for making customized zinc-finger arrays
    Morgan L Maeder
    Molecular Pathology Unit, Center for Cancer Research, and Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, Massachusetts, USA
    Nat Protoc 4:1471-501. 2009
    ..Here we provide a detailed protocol for carrying out OPEN to engineer zinc-finger arrays that have a high probability of functioning as ZFNs. Using OPEN, researchers can generate multiple, customized ZFNs in approximately 8 weeks...
  47. pmc Introduction of Culex toxicity into Bacillus thuringiensis Cry4Ba by protein engineering
    Mohd Amir F Abdullah
    The Protein Research Group, The Ohio State University, Columbus, Ohio, USA
    Appl Environ Microbiol 69:5343-53. 2003
    ..thuringiensis Cry toxins...
  48. ncbi Affibody molecules: engineered proteins for therapeutic, diagnostic and biotechnological applications
    J Löfblom
    Department of Molecular Biotechnology, School of Biotechnology, Royal Institute of Technology KTH, AlbaNova University Center, Stockholm, Sweden
    FEBS Lett 584:2670-80. 2010
    ..Cumulative evidence suggests that the three helical scaffold domain used as basis for these molecules is highly suited to create a molecular affinity handle for vastly different applications...
  49. pmc Surface sites for engineering allosteric control in proteins
    Jeeyeon Lee
    Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA
    Science 322:438-42. 2008
    ..PAS-DHFR serves as a proof of concept for engineering regulatory activities into proteins through interface design at conserved allosteric sites...
  50. ncbi Meganucleases and DNA double-strand break-induced recombination: perspectives for gene therapy
    Frédéric Pâques
    Cellectis SA, 102, route de Noisy, 93 340 Romainville Cedex France
    Curr Gene Ther 7:49-66. 2007
    ..Finally, we will discuss the main issues that will need to be addressed in order to bring this promising technology to the patient...
  51. ncbi Isolating and engineering human antibodies using yeast surface display
    Ginger Chao
    Department of Chemical Engineering and Biological Engineering Division, Massachusetts Institute of Technology, 77 Massachusetts Avenue E19 563, Cambridge, Massachusetts 02139, USA
    Nat Protoc 1:755-68. 2006
    ..The ultimate result of following this protocol is a panel of scFvs with increased stability and affinity for an antigen of interest...
  52. pmc Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity
    Ekkehard Mössner
    GLYCART biotechnology AG, Schlieren, Switzerland
    Blood 115:4393-402. 2010
    ..Taken together, these results provide compelling evidence for the development of GA101 as a promising new therapy for the treatment of B-cell disorders...
  53. ncbi High-throughput generation of synthetic antibodies from highly functional minimalist phage-displayed libraries
    Frederic A Fellouse
    Department of Protein Engineering, Genentech Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    J Mol Biol 373:924-40. 2007
    ....
  54. pmc Engineering variants of the I-SceI homing endonuclease with strand-specific and site-specific DNA-nicking activity
    Yan Niu
    Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA
    J Mol Biol 382:188-202. 2008
    ....
  55. pmc Generation of a nicking enzyme that stimulates site-specific gene conversion from the I-AniI LAGLIDADG homing endonuclease
    Audrey McConnell Smith
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue, North Seattle, WA 98109, USA
    Proc Natl Acad Sci U S A 106:5099-104. 2009
    ..The development of sequence-specific nicking enzymes like the I-AniI nickase will facilitate comparative analyses of DNA repair and mutagenesis induced by single- or double-strand breaks...
  56. ncbi Development of zinc finger domains for recognition of the 5'-CNN-3' family DNA sequences and their use in the construction of artificial transcription factors
    Birgit Dreier
    The Skaggs Institute for Chemical Biology, La Jolla, California 92037, USA
    J Biol Chem 280:35588-97. 2005
    ..With the addition of this collection of predefined zinc finger domains, most 5'-CNN-3'-, 5'-GNN-3'-, and 5'-ANN-3'-containing sequences can now be rapidly targeted for directed gene regulation and nuclease cleavage...
  57. pmc Zinc-finger recombinase activities in vitro
    Marko M Prorocic
    Institute of Infection, Immunity and Inflammation, University of Glasgow, GBRC, Glasgow G12 8QQ, Scotland, UK
    Nucleic Acids Res 39:9316-28. 2011
    ..We discuss the causes of these phenomena, and their implications for practical applications of ZFRs...
  58. pmc High-throughput thermal scanning: a general, rapid dye-binding thermal shift screen for protein engineering
    Jason J Lavinder
    Ohio State Biochemistry Program, Department of Chemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210, USA
    J Am Chem Soc 131:3794-5. 2009
    ..This inexpensive, general, and scaleable approach enables the search for conservative, stable mutants of biotechnologically important proteins and provides a method for statistical correlation of sequence-stability relationships...
  59. pmc Immunoglobulin domain crossover as a generic approach for the production of bispecific IgG antibodies
    Wolfgang Schaefer
    Biologics Research, Pharma Research and Early Development, Roche Diagnostics GmbH, D 82372 Penzberg, Germany
    Proc Natl Acad Sci U S A 108:11187-92. 2011
    ..Because of its superior side-product profile, the CrossMab(CH1-CL) was selected for in vivo profiling and showed potent antiangiogenic and antitumoral activity...
  60. pmc A novel strategy to engineer DNA polymerases for enhanced processivity and improved performance in vitro
    Yan Wang
    Department of Research and Development, MJ Bioworks Inc, 7000 Shoreline Court, South San Francisco, CA 94080, USA
    Nucleic Acids Res 32:1197-207. 2004
    ..Here we report a protein engineering-based approach to significantly improve the processivity of DNA polymerases by covalently linking the ..
  61. pmc Engineering global regulator Hha of Escherichia coli to control biofilm dispersal
    Seok Hoon Hong
    Department of Chemical Engineering, Texas A and M University, College Station, TX 77843 3122, USA
    Microb Biotechnol 3:717-28. 2010
    ..Hha variant Hha24E9 (K62X) was also obtained that decreased biofilm formation by inducing gadW, glpT and phnF but that did not alter biofilm dispersal. Hence, Hha may be engineered to influence both biofilm dispersal and formation...
  62. ncbi Modulation of the effector functions of a human IgG1 through engineering of its hinge region
    William F Dall'Acqua
    Department of Antibody Discovery and Protein Engineering, MedImmune, One MedImmune Way, Gaithersburg, MD 20878, USA
    J Immunol 177:1129-38. 2006
    ..We also define, for the first time in such a systematic fashion, the relationship between various characteristics of the middle and upper hinge and the corresponding effector functions...
  63. pmc Computational thermostabilization of an enzyme
    Aaron Korkegian
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center FHCRC, 1100 Fairview Avenue North, Seattle, WA 98109, USA
    Science 308:857-60. 2005
    ..The redesigned enzyme induced an increased, temperature-dependent bacterial growth rate under conditions that required its activity, thereby coupling molecular and metabolic engineering...
  64. ncbi Efficient tumor targeting with high-affinity designed ankyrin repeat proteins: effects of affinity and molecular size
    Christian Zahnd
    Universitat Zurich, Biochemisches Institut, Winterthurerstrasse, 8057 Zurich, Switzerland
    Cancer Res 70:1595-605. 2010
    ....
  65. ncbi Designing repeat proteins: well-expressed, soluble and stable proteins from combinatorial libraries of consensus ankyrin repeat proteins
    H Kaspar Binz
    Biochemisches Institut, Universitat Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    J Mol Biol 332:489-503. 2003
    ..Moreover, the favorable biophysical properties and the modularity of the AR fold may account, partly, for the abundance of natural AR proteins...
  66. ncbi A designed ankyrin repeat protein evolved to picomolar affinity to Her2
    Christian Zahnd
    Biochemisches Institut der Universitat Zurich, Winterthurerstr 190, CH 8057 Zurich, Switzerland
    J Mol Biol 369:1015-28. 2007
    ....
  67. pmc Zinc-finger protein-targeted gene regulation: genomewide single-gene specificity
    Siyuan Tan
    Sangamo BioSciences, Inc, Point Richmond Tech Center II, 501 Canal Boulevard, Richmond, CA 94804, USA
    Proc Natl Acad Sci U S A 100:11997-2002. 2003
    ..These data demonstrate the utility of ZFP TFs as precise tools for target validation, and highlight their potential as clinical therapeutics...
  68. pmc Rapid and highly efficient construction of TALE-based transcriptional regulators and nucleases for genome modification
    Lixin Li
    Division of Chemical and Life Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955 6900, Kingdom of Saudi Arabia
    Plant Mol Biol 78:407-16. 2012
    ..Our dTALE repeat assembly approach along with the web tool idTALE will expedite genome-engineering applications in a variety of cell types and organisms including plants...
  69. pmc RosettaDesign server for protein design
    Yi Liu
    Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA
    Nucleic Acids Res 34:W235-8. 2006
    ..RosettaDesign has been experimentally validated and has been used previously to stabilize naturally occurring proteins and design a novel protein structure...
  70. pmc Site-directed transposon integration in human cells
    Stephen R Yant
    Department of Pediatrics and Genetics, Stanford University School of Medicine, Stanford, CA 94305 5208, USA
    Nucleic Acids Res 35:e50. 2007
    ..These findings illustrate the feasibility of directed transposon integration and highlight potential means for future development...
  71. ncbi Kemp elimination catalysts by computational enzyme design
    Daniela Röthlisberger
    Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
    Nature 453:190-5. 2008
    The design of new enzymes for reactions not catalysed by naturally occurring biocatalysts is a challenge for protein engineering and is a critical test of our understanding of enzyme catalysis...
  72. ncbi Macromolecular modeling with rosetta
    Rhiju Das
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Annu Rev Biochem 77:363-82. 2008
    ..Emerging connections to crystallographic phasing, NMR modeling, and lower-resolution approaches are described and critically assessed...
  73. pmc Modular system for the construction of zinc-finger libraries and proteins
    Beatriz Gonzalez
    The Skaggs Institute for Chemical Biology, La Jolla, California, USA
    Nat Protoc 5:791-810. 2010
    ..We also describe the construction of a customized ZF-TF that can be transferred to a number of expression vectors. This protocol can be completed in 9-11 d...
  74. ncbi Optimization of humanized IgGs in glycoengineered Pichia pastoris
    Huijuan Li
    GlycoFi Inc 21 Lafayette Street, Lebanon, New Hampshire 03766, USA
    Nat Biotechnol 24:210-5. 2006
    ..Glycoengineered P. pastoris provides a general platform for producing recombinant antibodies with human N-glycosylation...
  75. pmc Generation of redesigned homing endonucleases comprising DNA-binding domains derived from two different scaffolds
    Sylvestre Grizot
    Cellectis SA, 102 Avenue Gaston Roussel, 93235 Romainville Cedex, France
    Nucleic Acids Res 38:2006-18. 2010
    ..The DmoCre based meganucleases can therefore offer new possibilities for various genome engineering applications...
  76. ncbi Circular permutation: a different way to engineer enzyme structure and function
    Ying Yu
    Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA 30322, USA
    Trends Biotechnol 29:18-25. 2011
    ....
  77. pmc An affinity-based scoring scheme for predicting DNA-binding activities of modularly assembled zinc-finger proteins
    Jeffry D Sander
    Department of Genetics, Development and Cell Biology, Bioinformatics and Computational Biology Program, Iowa State University, Ames, IA 50011, USA
    Nucleic Acids Res 37:506-15. 2009
    ..91). We propose that success rates for ZFP modular assembly can be significantly improved by exploiting the score-based strategy described here...
  78. pmc Engineering and identifying supercharged proteins for macromolecule delivery into mammalian cells
    David B Thompson
    Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA
    Methods Enzymol 503:293-319. 2012
    ..This chapter summarizes methods for engineering supercharged proteins, optimizing cell penetration, identifying naturally occurring supercharged proteins, and using these proteins for macromolecule delivery into mammalian cells...
  79. ncbi The generation of zinc finger proteins by modular assembly
    Mital S Bhakta
    Department of Pharmacology, Genome Center, University of California at Davis, Davis, CA, USA
    Methods Mol Biol 649:3-30. 2010
    ..Such ZFPs might be useful as starting materials to perform other methods described in this volume. Here, we also describe a single-strand annealing recombination assay for the initial testing of zinc finger nucleases...
  80. ncbi A universal code for RNA recognition by PUF proteins
    Aleksandra Filipovska
    Western Australian Institute for Medical Research and Centre for Medical Research, The University of Western Australia, Perth, Australia
    Nat Chem Biol 7:425-7. 2011
    ..These repeat sequences can be used to create PUF domains capable of selectively binding RNA targets of diverse sequence and structure...
  81. pmc Shortened engineered human antibody CH2 domains: increased stability and binding to the human neonatal Fc receptor
    Rui Gong
    Protein Interactions Group, Center for Cancer Research Nanobiology Program, Center for Cancer Research, National Institutes of Health, Frederick, Maryland 21702, USA
    J Biol Chem 286:27288-93. 2011
    ....
  82. pmc Targeted mutagenesis in zebrafish using customized zinc-finger nucleases
    Jonathan E Foley
    Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA
    Nat Protoc 4:1855-67. 2009
    ..Using these methods, zebrafish founders carrying targeted mutations can be identified within 4 months...
  83. pmc TRITON: a graphical tool for ligand-binding protein engineering
    Martin Prokop
    National Centre for Biomolecular Research and Department of Biochemistry, Faculty of Science, Masaryk University, Kotlarska 2, 611 37 Brno, Czech Republic
    Bioinformatics 24:1955-6. 2008
    ..TRITON can now be used to design ligand-binding proteins, to study protein-ligand binding mechanisms or simply to dock any ligand to a protein...
  84. ncbi A recombinant polypeptide extends the in vivo half-life of peptides and proteins in a tunable manner
    Volker Schellenberger
    Amunix, Inc, Mountain View, California, USA
    Nat Biotechnol 27:1186-90. 2009
    ..Based on data on XTEN fusions to exenatide, glucagon, GFP and human growth hormone, we expect that XTEN will enable dosing of otherwise rapidly cleared protein drugs at up to monthly intervals in humans...
  85. ncbi Moss bioreactors producing improved biopharmaceuticals
    Eva L Decker
    Plant Biotechnology, Faculty of Biology, University of Freiburg, Schaenzlestr 1, D 79104 Freiburg, Germany
    Curr Opin Biotechnol 18:393-8. 2007
    ..By targeted gene replacements, moss strains were created with non-immunogenic humanised glycan patterns. These were proven to be superior to currently used mammalian cell lines in producing antibodies with enhanced effectiveness...
  86. ncbi Post-translational modifications of protein biopharmaceuticals
    Gary Walsh
    Department of Chemical and Environmental Sciences and the Materials and Surface Science Institute, University of Limerick, Limerick City, Ireland
    Drug Discov Today 15:773-80. 2010
    ..This review considers the PTMs most often associated with therapeutic proteins and focuses upon more recent advances in engineering PTMs with the aim of improving the application-relevant functional characteristics of these drugs...
  87. ncbi Evaluation of a modular strategy for the construction of novel polydactyl zinc finger DNA-binding proteins
    David J Segal
    The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Biochemistry 42:2137-48. 2003
    ..These results have important implications for the design of proteins that can recognize extended DNA sequences, as well as provide insights into the general rules of recognition for naturally occurring zinc finger proteins...
  88. ncbi Protein engineering to stabilize soluble amyloid β-protein aggregates for structural and functional studies
    Torleif Härd
    Department of Molecular Biology, Swedish University of Agricultural Sciences SLU, Uppsala, Sweden
    FEBS J 278:3884-92. 2011
    ..Here we review recent studies in which protein engineering, and in particular disulfide engineering, has been applied to stabilize different Aβ aggregates...
  89. pmc Overcoming transcription activator-like effector (TALE) DNA binding domain sensitivity to cytosine methylation
    Julien Valton
    CELLECTIS S A, 8 rue de la croix Jarry, 75013 Paris, France
    J Biol Chem 287:38427-32. 2012
    ..Using a combination of biochemical, structural, and cellular approaches, we were able to identify the molecular basis of such sensitivity and propose a simple, drug-free, and universal method to overcome it...
  90. pmc Broad neutralization of human immunodeficiency virus type 1 (HIV-1) elicited from human rhinoviruses that display the HIV-1 gp41 ELDKWA epitope
    Gail Ferstandig Arnold
    Center for Advanced Biotechnology and Medicine, 679 Hoes Lane, Piscataway, NJ 08854 5638, USA
    J Virol 83:5087-100. 2009
    ....
  91. ncbi Effects of charge on antibody tissue distribution and pharmacokinetics
    C Andrew Boswell
    Department of Pharmacokinetic and Pharmacodynamic Sciences, Genentech Research and Early Development, South San Francisco, California 94080, USA
    Bioconjug Chem 21:2153-63. 2010
    ....
  92. ncbi Lantibiotics: peptides of diverse structure and function
    Joanne M Willey
    Department of Biology, Hofstra University, Hempstead, New York 11549, USA
    Annu Rev Microbiol 61:477-501. 2007
    ..collection of molecules and introduce some recently discovered peptides, review advances in enzymology and protein engineering, and discuss the regulatory networks that govern the synthesis of the lantibiotics by the producing ..
  93. ncbi Biosimilar, biobetter, and next generation antibody characterization by mass spectrometry
    Alain Beck
    Centre d Immunologie Pierre Fabre CIPF, 5 Av Napoleon III, BP 60497, 74164 Saint Julien en Genevois, France
    Anal Chem 84:4637-46. 2012
    ..In addition, the structural and functional insights gained both by state-of-the art and emerging MS methods used for biobetters and next generation antibodies design and optimization will also be highlighted...
  94. ncbi Expanding the genetic code of Escherichia coli with phosphoserine
    Hee Sung Park
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    Science 333:1151-4. 2011
    ..This system has general utility in protein engineering, molecular biology, and disease research.
  95. pmc Targeted manipulation of mammalian genomes using designed zinc finger nucleases
    Karthikeyan Kandavelou
    Department of Environmental Health Sciences, Johns Hopkins School of Public Health, Baltimore, MD 21205, USA
    Biochem Biophys Res Commun 388:56-61. 2009
    ..Furthermore, re-engineered obligate heterodimer FokI nuclease domain variants appear to completely eliminate or greatly reduce the toxicity of ZFNs to mammalian cells, including human cells...
  96. ncbi A glycoengineered anti-CD19 antibody with potent antibody-dependent cellular cytotoxicity activity in vitro and lymphoma growth inhibition in vivo
    Elizabeth Ward
    Department of Research, MedImmune, LLC, Gaithersburg, MD 20787, USA
    Br J Haematol 155:426-37. 2011
    ..The results also suggest that the combination of the ADCC-enhanced CD19 mAb with an anti-CD20 mAb could be a novel approach for the treatment of B cell lymphomas...
  97. pmc Tetravalent single-chain avidin: from subunits to protein domains via circularly permuted avidins
    Henri R Nordlund
    Department of Biological and Environmental Science, Nanoscience Center, P O Box 35 YAB, FIN 40014 University of Jyväskylä, Finland
    Biochem J 392:485-91. 2005
    ..avidin monomers, scAvd enables each one of the four avidin domains to be independently modified by protein engineering. Therefore the scAvd scaffold can be used to construct spatially and stoichiometrically defined ..
  98. pmc Stabilization of neurotoxic Alzheimer amyloid-beta oligomers by protein engineering
    Anders Sandberg
    Institute of Biomedicine, University of Gothenburg, SE 405 30 Gothenburg, Sweden
    Proc Natl Acad Sci U S A 107:15595-600. 2010
    ....
  99. pmc Evaluation of a (64)Cu-labeled cystine-knot peptide based on agouti-related protein for PET of tumors expressing alphavbeta3 integrin
    Lei Jiang
    Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, China
    J Nucl Med 51:251-8. 2010
    ..In this study, we evaluated the potential of engineered integrin-binding AgRP peptides for use as cancer imaging agents in living subjects...
  100. pmc An engineered knottin peptide labeled with 18F for PET imaging of integrin expression
    Zheng Miao
    Molecular Imaging Program at Stanford MIPS, Bio X Program, Stanford University, Stanford, California 94305, USA
    Bioconjug Chem 20:2342-7. 2009
    ..5D allows integrin-specific PET imaging of U87MG tumors with good contrast and further demonstrates that knottins are excellent peptide scaffolds for development of PET probes with potential for clinical translation...
  101. pmc Antigen specificity of gammadelta T cells depends primarily on the flanking sequences of CDR3delta
    Xueyan Xi
    Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Peking Union Medical College, National Key Laboratory of Medical Molecular Biology, Beijing 100005, China
    J Biol Chem 284:27449-55. 2009
    ..Our results demonstrate that TCRdelta primarily uses conserved flanking regions to bind ligands. This finding may provide an explanation for the limited number of gammadelta TCR ligands that have as yet been identified...

Research Grants77

  1. STRUCTURE & FUNCTION RELATIONSHIP: PROSTANOID RECEPTORS
    Ke He Ruan; Fiscal Year: 2008
    ..Determine the solution conformation of segments comprising the intracellular domains. ..
  2. Prostaglandin I synthase, Thromboxane A synthase & Prostaglandin E synthase
    Ke He Ruan; Fiscal Year: 2009
    ....
  3. High-avidity multimeric cancer imaging agent
    Anna Wu; Fiscal Year: 2005
    ..In particular, through protein engineering, recombinant antibody fragments can be produced that are optimized for in vivo tumor targeting, blood ..
  4. Cloning and Engineering of Nicking enzymes
    Shuang yong Xu; Fiscal Year: 2004
    ..abstract_text> ..
  5. Engineering DNA nicking endonucleases
    Shuang yong Xu; Fiscal Year: 2006
    ..Under Phase II funding, this isothermal amplification method (NEMDA) will be optimized and the sensitivity will be improved. Finally, we will investigate the potential of NEMDA for detections of pathogens and its use in bio-prospecting. ..
  6. A universal DNA endonuclease
    Shuang yong Xu; Fiscal Year: 2005
    ..For isothermal applications of the universal nuclease at 50oC-70oC, the nuclease domain will be derived from thermophilic endonucleases. ..
  7. Conference Proposal: FASEB Nucleic Acid Enzymes
    Barry Stoddard; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  8. Structural studies of blood coagulation proteins
    Barry Stoddard; Fiscal Year: 2006
    ..The third specific aim for this project is to determine the structure of the N-terminal, D'-D3 domain from von Willebrand Factor, alone and/or in complex with factor VIII heterodimer. ..
  9. A Genetic System Able to Screen for Active DNA Demethylation
    Shuang yong Xu; Fiscal Year: 2006
    ..In addition, knowledge of the mechanism of demethylation could be crucial in converting fully differentiated adult stem cells into totipotent stem cells. [unreadable] [unreadable] [unreadable]..
  10. Engineering enzymes for anti-tumor suicide gene therapy
    Barry L Stoddard; Fiscal Year: 2010
    ..the project follows a 'design cycle'of crystallographic structure determination, computational protein engineering, directed evolution and subsequent kinetic and structural analyses...
  11. STRUCTURE AND STABILITY OF SINGLE-LAYER BETA-SHEETS
    Shohei Koide; Fiscal Year: 2005
    ..techniques including NMR spectroscopy, small angle X-ray scattering and differential scanning calorimetry, protein engineering and combinatorial library screening...
  12. Plant Biofilm Inhibitors to Discover Biofilm Genes
    Thomas Wood; Fiscal Year: 2008
    ..deduce a model for bacterial biofilm formation based on the genetic information (which genes induced/repressed) and protein information discerned (via NMR) ..
  13. Nuclear receptor probed with designer binding proteins
    Shohei Koide; Fiscal Year: 2005
    ..We expect that results from this project will fill a large gap that presently exists between out knowledge gained from the static ..
  14. Creation of site-specific DNA methyltransferases
    Marc Ostermeier; Fiscal Year: 2006
    ..A novel combinatorial protein engineering approach coupled with directed evolution will be used to created these site-specific methyltransferases...
  15. Stimulating Gene Targeting with Zinc Finger Nucleases
    Dana Carroll; Fiscal Year: 2004
    ..To demonstrate the generality of this approach to gene targeting, it will be applied to another mouse locus, the Rpo2-1 gene. ..
  16. A Genome-Derived, Epitope-Driven H. Pylori Vaccine
    Anne De Groot; Fiscal Year: 2006
    ..pylori disease as our correlate of efficacy. ..
  17. SIGNALING AND ANTITUMOR EFFECTS OF ANTIBODIES
    Ellen Vitetta; Fiscal Year: 2001
    ..These tumors will be used as targets for therapy. To this end, she has initiated collaborations at her institution and at two other institutions for the acquisition of fresh lymphomas. ..
  18. Chimeric Nucleases for Gene Targeting in Drosophila
    Dana Carroll; Fiscal Year: 2003
    ..To test the generality of the method, it will be applied to a second Drosophila locus, the rosy (ry) gene. ..
  19. A GENOME-DERIVED, EPITOPE-DRIVEN TULAREMIA VACCINE
    Anne De Groot; Fiscal Year: 2005
    ..abstract_text> ..
  20. A Novel Recombinant Protein Vaccine Against Ricin Toxin
    Ellen Vitetta; Fiscal Year: 2006
    ..When these three aims are completed, the vaccine should be ready for acute toxicology studies in two species and scale-up for Phase 1 clinical trials in humans. [unreadable] [unreadable]..
  21. Non-Viral Gene Targeting to the Brain
    William Pardridge; Fiscal Year: 2008
    ..abstract_text> ..
  22. RNA EDITING IN PLANT ORGANELLES
    Maureen Hanson; Fiscal Year: 2001
    ..The proposed research should enhance understanding of other forms of RNA processing in the biological world, especially the mechanisms of tRNA, mRNA and rRNA modification and editing. ..
  23. Development of De-immunized Botulinum Neurotoxin Type A for Dystonia
    Anne De Groot; Fiscal Year: 2008
    ..Public Health Relatedness: Knowledge of the elements of botulinum neurotoxin type A that give rise to its immunogenicity will contribute to the development of improved dystonia therapy. [unreadable] [unreadable] [unreadable]..
  24. HLA-DQ-derived RTLs for Treatment of Celiac Disease
    GREGORY BURROWS; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  25. Gene therapy vectors for pediatric brain disease
    Anne Messer; Fiscal Year: 2003
    ..Once this assay system is in place for one vector, it can also be used to test modifications of vector specificity and expression, as well as additional vectors such as AAV complexes. ..
  26. Probing the pore of CFTR using chemical modification
    Xuehong Liu; Fiscal Year: 2003
    ..mechanism to explain how HFS type diets cause insulin resistance. and hypertension, and how a LFCC diet, antioxidant therapy or exercise training aid in the control of insulin resistance and hypertension. ..
  27. Characterizing Oral Cancer Progression via Saliva Proteomics
    Timothy J Griffin; Fiscal Year: 2010
    ..As such the findings from the proposed studies will have a direct impact on improving the diagnosis and treatment of oral cancer in the clinic, thereby leading to a decrease in the significant suffering and death caused by this cancer. ..
  28. IMMUNOTOXIN-DEPLETION OF HIV-1+T CELLS
    Ellen Vitetta; Fiscal Year: 2003
    ..This is a preclinical study to evaluate a new therapeutic modality. Our results should determine the feasibility of a future clinical trial. ..
  29. Consortium for Enhancing Human Subject Research Oversite
    LEONARD ROME; Fiscal Year: 2003
    ..Creating an open source modifiable application will not only meet the high volume and extensive IRB demands of our consortium, but will likely provide a viable solution to a large number of other institutions as well. ..
  30. Molecular Complementation of Nuclear Receptors
    John T Koh; Fiscal Year: 2010
    ..We will further develop these "functionally orthogonal" estrogen/ER pairs as novel chemical biology tools for dissecting the seven or more estrogen dependent signaling pathways. ..
  31. AFP-BASED PRIME-BOOST IMMUNOTHERAPY OF HCC
    LISA BUTTERFIELD; Fiscal Year: 2006
    ..These proposed studies will permit us to determine the immunological impact of a plasmid prime-adenoviral boost directed towards a self tumor antigen and to define mechanisms of antigen presentation. ..
  32. Drug development of an Alzheimer's disease brain scan
    RUBEN BOADO; Fiscal Year: 2005
    ..The AD brain scan may allow for the early detection of those individuals at risk for later development of brain amyloid and AD, and allow for early drug therapy. ..
  33. Structure of signal peptide peptidase
    RAQUEL LIEBERMAN; Fiscal Year: 2008
    ..This first structure of an intramembrane protease will provide critical insight into the biochemistry of intramembrane proteolysis and enable structure- based AD drug development and screening. ..
  34. Centriole Orientation During Left/Right Symmetry Breaking in the Mouse
    Wallace Marshall; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  35. Live Cell Fluorescence Imaging Using Molecular Switches
    Marc Ostermeier; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  36. Rhabdovirus phosphoproteins: RNA silencing and complex formation
    Michael Goodin; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  37. Stroke neuroprotection with a recombinant fusion protein
    RUBEN BOADO; Fiscal Year: 2007
    ..The completion of the phase II work will enable the preparation of an IND to the FDA for testing of this novel neuroprotective agent in acute stroke in humans. [unreadable] [unreadable] [unreadable] [unreadable]..
  38. Engineering high affinity integrin binding proteins
    Jennifer Cochran; Fiscal Year: 2008
    ..Promising antibodies will be engineered to ultra high affinity and stability using yeast surface display to develop potent integrin antagonists. ..
  39. Simulations of Calcium Selectivity and Binding
    Robert Eisenberg; Fiscal Year: 2009
    ..We will use these computations to design highly selective Ca channels of medical and technological interest. The simulations will suggest what needs to be improved in theory and design. ..
  40. ER Chaperone Availability in Cells During Homeostasis and Misfolded Protein Stres
    Erik L Snapp; Fiscal Year: 2010
    ..We are studying, at the cellular level, the mechanisms that maintain and regulate the secretory protein folding environment. ..
  41. GenMAPP-CS, a dynamic resource pathway analysis
    Bruce R Conklin; Fiscal Year: 2010
    ..The challenge of analyzing these massive and complex datasets is a major force driving the development of GenMAPP-CS. ..
  42. Broad Neutralization of HIV-1 from Rhinoviruses Displaying gp41 MPER Sequences
    GAIL ARNOLD; Fiscal Year: 2009
    ....
  43. Study of Actinobacillus Actinomycetemcomitans Virulence
    JOSEPH DIRIENZO; Fiscal Year: 2008
    ..abstract_text> ..
  44. Targeted Neurotrophin Drug Development in Parkinson's Disease
    RUBEN BOADO; Fiscal Year: 2008
    ..This research will lead to a new neurotrophin treatment of PD, which can be administered by intravenous or subcutaneous administration. [unreadable] [unreadable] [unreadable]..
  45. The Nano-mechanics of Polycystin-1
    ANDRES FERNANDO OBERHAUSER; Fiscal Year: 2010
    ..In Aim 3 we will use protein engineering and computer simulations to develop a molecular model for PC1-ectodomain to examine the significance of its ..
  46. Intrabodies as novel neurological therapeutics
    Anne Messer; Fiscal Year: 2010
    ..These approaches should also be generally applicable for other neurodegenerative diseases that result from abnormal protein folding and accumulation, including Alzheimer's, Parkinson's, and prion diseases. ..
  47. Sugar signaling networks detected by high content fluxomics
    Wolf B Frommer; Fiscal Year: 2010
    ..The networks and databases developed in this project promise to provide novel screening methods for novel drugs as well as help identifying new drug targets. ..
  48. Rapid protein crystallization by surface mutagenesis
    Zygmunt Derewenda; Fiscal Year: 2004
    ..Funds are requested to further test the general applicability and success rate of this method, and to apply the method to a subset of targets selected for the Structural Genomic Initiative. ..
  49. Antisense imaging of brain gene expression in vivo
    William Pardridge; Fiscal Year: 2005
    ..This technology could be extended to humans and to other organs. At present, there is no parallel technology that enables the non-invasive in vivo imaging of "any gene in any person," which is the goal of this work. ..
  50. NOVEL MHC CLASS II CONSTRUCTS FOR TREATMENTS OF CBD
    GREGORY BURROWS; Fiscal Year: 2003
    ....
  51. The role of TNF receptor family in intestinal GVHD
    GERI BROWN; Fiscal Year: 2004
    ..abstract_text> ..
  52. BD FACSARIA FLOW CYTOMETER 3 LSR W/ACDU
    Patrick Daugherty; Fiscal Year: 2004
    ....
  53. Preparing high resolution membrane protein crystals
    Zygmunt Derewenda; Fiscal Year: 2005
    ..abstract_text> ..
  54. REGULATION OF BBB GLUT1 GLUCOSE TRANSPORTER
    William Pardridge; Fiscal Year: 2002
    ..These studies will provide insight into molecular mechanisms of regulation of a step crucial to the maintenance of cerebral intermediary metabolism, i.e., the continuous transport of glucose across the blood-brain barrier in vivo. ..
  55. COLLABORATIVE R01--ROLES OF G PROTEINS IN CARDIOMYOPATHY
    Bruce Conklin; Fiscal Year: 2002
    ..3. To selectively activate G protein pathways in the setting of two experimentally induced cardiomyopathy models where G protein signaling has been shown to be altered. (End of Abstract) ..
  56. MHC Class l-independent NK Cell Regulation
    Koho Iizuka; Fiscal Year: 2006
    ..2) Determine the role of Nkrpl/Clr genes in NK cell development. These studies are critical to our understanding of innate immunity and improving the manipulation of NK cells for therapeutic purposes. ..
  57. The reversal of multidrug resistance by an anti-CD19 ab.
    Ellen Vitetta; Fiscal Year: 2006
    ..abstract_text> ..
  58. GENOMIC ENZYMOLOGY: THE ENOLASE SUPERFAMILY
    JOHN GERLT; Fiscal Year: 2006
    ..4) We will test a structural blueprint for functional diversity in the (beta/alpha)7beta-barrel fold by determining whether new functions can be generated by in vitro evolution. ..
  59. GenMAPP: A tool for pathway analysis of genomic data
    Bruce Conklin; Fiscal Year: 2006
    ..With the completion these aims, GenMAPP 3.0 will provide a program that is robust, simple to use, and available without charge to the entire biological community. [unreadable] [unreadable]..
  60. CONSTRUCTION OF MAGNETIC RESONNANCE CENTER
    LEONARD ROME; Fiscal Year: 2002
    ..abstract_text> ..
  61. SCREEN FOR TUMOR SUPPRESSORS ON MOUSE CHROMOSOME 4
    Allan Bradley; Fiscal Year: 2001
    ..The pro-viral tag will facilitate the molecular identification of insertionally inactivated tumor suppressor genes in these cell lines. ..
  62. CFTR: Probing the Gating Related Movements in the Pore
    Xuehong Liu; Fiscal Year: 2007
    ....
  63. Photo-Inducible Transcriptional Regulators
    John Koh; Fiscal Year: 2007
    ..abstract_text> ..
  64. Immunobiological Role of Fertilization Antigen(FA-1)
    RAJESH NAZ; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  65. Human MHC Class II Constructs For Autoimmume Therapy
    GREGORY BURROWS; Fiscal Year: 2005
    ..Understanding how these unique, rationally engineered drugs work will provide a solid foundation for pharmacological intervention in CD4+ T cell mediated autoimmune diseases. ..
  66. PROTEIN INTERACTIONS REGULATING CELL MOTILITY
    Wendell Lim; Fiscal Year: 2009
    ....
  67. Pathogen-specific drug targets for weaponized bacteria
    Vincent Fischetti; Fiscal Year: 2007
    ..In total, these efforts target central virulence factors in critical biowarfare pathogens. ..
  68. Retrovectors for Intron-Enhanced Protein Expression
    Michael Imboden; Fiscal Year: 2005
    ..abstract_text> ..
  69. Delivery Systems for Precision Brain Cell Targeting
    Scott Banta; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  70. Mobilization of Candida albicans Biofilms
    Peter Suci; Fiscal Year: 2007
    ..albicans biofilm communities, it will provide the basis for development of methods for screening for adjuvant agents that will inhibit dissemination of these fungal infections. [unreadable] [unreadable] [unreadable]..
  71. UCB-DERIVED CD19-SPECIFIC T CELLS FOR UNIVERSAL TREATMENT OF B-CELL MALIGNANCY
    LAURENCE COOPER; Fiscal Year: 2008
    ..Lav language: T cells will be developed which can destroy B-lineage disease. [unreadable] [unreadable] [unreadable]..
  72. Characterization of A Novel 65kDa E-selectin Ligand on G-CSF Mobilized Leukocytes
    Robert Sackstein; Fiscal Year: 2008
    ..It is anticipated that the results obtained will lead to new approaches for preventing or alleviating G-CSF-induced vascular and inflammatory complications [unreadable] [unreadable] [unreadable]..
  73. CD19-Specific T-Cell Therapy for Follicular Lymphoma
    LAURENCE COOPER; Fiscal Year: 2004
    ....
  74. Structure & Biology of Hematopoietic E-/L-Selectin
    Robert Sackstein; Fiscal Year: 2006
    ..This information will contribute greatly to our understanding of the adhesive systems that regulate steady-state and pathologic hematopoiesis, as well as hematopoietic recovery following stem cell transplantation. ..
  75. Imaging Infused CD19 Specific T Cells in the Tumor
    LAURENCE COOPER; Fiscal Year: 2008
    ..This will help investigators gauge the efficacy of T-cell immunotherapies. [unreadable] [unreadable] [unreadable]..
  76. ADHESION MOLECULES MEDIATING SKIN TROPISM IN ACUTE GVHD
    Robert Sackstein; Fiscal Year: 2003
    ....