integrases

Summary

Summary: Recombinases that insert exogenous DNA into the host genome. Examples include proteins encoded by the POL GENE of RETROVIRIDAE and also by temperate BACTERIOPHAGES, the best known being BACTERIOPHAGE LAMBDA.

Top Publications

  1. ncbi Generalized lacZ expression with the ROSA26 Cre reporter strain
    P Soriano
    Nat Genet 21:70-1. 1999
  2. pmc Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus
    S Srinivas
    Department of Genetics and Development, Columbia University, New York, USA
    BMC Dev Biol 1:4. 2001
  3. pmc An optimized transgenesis system for Drosophila using germ-line-specific phiC31 integrases
    Johannes Bischof
    Frontiers in Genetics, National Center of Competence in Research, Institute of Molecular Biology, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    Proc Natl Acad Sci U S A 104:3312-7. 2007
  4. pmc A robust and high-throughput Cre reporting and characterization system for the whole mouse brain
    Linda Madisen
    Allen Institute for Brain Science, Seattle, Washington, USA
    Nat Neurosci 13:133-40. 2010
  5. ncbi A global double-fluorescent Cre reporter mouse
    Mandar Deepak Muzumdar
    Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA
    Genesis 45:593-605. 2007
  6. ncbi Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system
    Jean Livet
    Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA
    Nature 450:56-62. 2007
  7. ncbi Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety
    F Tronche
    Molecular Biology of the Cell I, Deutsches Krebsforschungzentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
    Nat Genet 23:99-103. 1999
  8. pmc Construction of transgenic Drosophila by using the site-specific integrase from phage phiC31
    Amy C Groth
    Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA
    Genetics 166:1775-82. 2004
  9. ncbi Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible form of Cre recombinase
    P S Danielian
    Department of Molecular and Cellular Biology Harvard University 16 Divinity Avenue, Cambridge Massachusetts 02138 USA
    Curr Biol 8:1323-6. 1998
  10. ncbi Inducible gene targeting in mice
    R Kuhn
    Institute for Genetics, University of Cologne, Germany
    Science 269:1427-9. 1995

Research Grants

  1. Integration and Excision by Serine Intergrases
    Graham F Hatfull; Fiscal Year: 2013
  2. CODA Assembly of Mutant Genes
    SHE PIN contact HUNG; Fiscal Year: 2010
  3. Crystallographic Studies of Retroviral Integrases
    Hideki Aihara; Fiscal Year: 2013
  4. Crystallographic Studies of Retroviral Integrases
    Hideki Aihara; Fiscal Year: 2010
  5. Structural understanding of Mu transposition
    Phoebe A Rice; Fiscal Year: 2013
  6. Structure/Function Analysis of the Retrovirus Integrase
    JONATHAN P LEIS; Fiscal Year: 2010
  7. SUBSTRATE INTERACTIONS OF A MULTIFUNCTIONAL INTEGRASE
    Michael Katzman; Fiscal Year: 2000
  8. Phenotypes of HIV-1 Integrases
    William Robinson; Fiscal Year: 2009
  9. Targeted Transgene Integration through Chromatin tethering for Globin Gene Therap
    ANDRE MICHAEL LIEBER; Fiscal Year: 2010
  10. IMPROVED ADENOVIRAL VECTORS FOR HEPATIC GENE THERAPY
    Mark Kay; Fiscal Year: 2006

Detail Information

Publications281 found, 100 shown here

  1. ncbi Generalized lacZ expression with the ROSA26 Cre reporter strain
    P Soriano
    Nat Genet 21:70-1. 1999
  2. pmc Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus
    S Srinivas
    Department of Genetics and Development, Columbia University, New York, USA
    BMC Dev Biol 1:4. 2001
    ....
  3. pmc An optimized transgenesis system for Drosophila using germ-line-specific phiC31 integrases
    Johannes Bischof
    Frontiers in Genetics, National Center of Competence in Research, Institute of Molecular Biology, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    Proc Natl Acad Sci U S A 104:3312-7. 2007
    ....
  4. pmc A robust and high-throughput Cre reporting and characterization system for the whole mouse brain
    Linda Madisen
    Allen Institute for Brain Science, Seattle, Washington, USA
    Nat Neurosci 13:133-40. 2010
    ..Our expression data are displayed in a public online database to help researchers assess the utility of various Cre-driver lines for cell-type-specific genetic manipulation...
  5. ncbi A global double-fluorescent Cre reporter mouse
    Mandar Deepak Muzumdar
    Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA
    Genesis 45:593-605. 2007
    ..In addition to serving as a global Cre reporter, the mT/mG mouse may also be used as a tool for lineage tracing, transplantation studies, and analysis of cell morphology in vivo...
  6. ncbi Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system
    Jean Livet
    Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA
    Nature 450:56-62. 2007
    ..The ability of the Brainbow system to label uniquely many individual cells within a population may facilitate the analysis of neuronal circuitry on a large scale...
  7. ncbi Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety
    F Tronche
    Molecular Biology of the Cell I, Deutsches Krebsforschungzentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
    Nat Genet 23:99-103. 1999
    ..Conditional mutagenesis of Gr in the nervous system provides genetic evidence for the importance of Gr signalling in emotional behaviour because mutant animals show an impaired behavioural response to stress and display reduced anxiety...
  8. pmc Construction of transgenic Drosophila by using the site-specific integrase from phage phiC31
    Amy C Groth
    Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA
    Genetics 166:1775-82. 2004
    ..These experiments demonstrate the potential for precise genetic engineering of the Drosophila genome with the phiC31 integrase system and will likely benefit research in Drosophila and other insects...
  9. ncbi Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible form of Cre recombinase
    P S Danielian
    Department of Molecular and Cellular Biology Harvard University 16 Divinity Avenue, Cambridge Massachusetts 02138 USA
    Curr Biol 8:1323-6. 1998
    ..Induction was ligand dependent, rapid and efficient. The results demonstrate that tamoxifen-inducible recombination can be used to effectively modify gene function in the mouse embryo...
  10. ncbi Inducible gene targeting in mice
    R Kuhn
    Institute for Genetics, University of Cologne, Germany
    Science 269:1427-9. 1995
    ..Deletion was complete in liver and nearly complete in lymphocytes within a few days, whereas partial deletion was obtained in other tissues. This method can be used for the inducible inactivation of any other gene in vivo...
  11. pmc Retroviral intasome assembly and inhibition of DNA strand transfer
    Stephen Hare
    Division of Medicine, Imperial College London, St Mary s Campus, Norfolk Place, London W2 1PG, UK
    Nature 464:232-6. 2010
    ..Our findings define the structural basis of retroviral DNA integration, and will allow modelling of the HIV-1 intasome to aid in the development of antiretroviral drugs...
  12. ncbi Transgenic mice with hematopoietic and lymphoid specific expression of Cre
    Jasper de Boer
    Department of Molecular Immunology, National Institute for Medical Research, The Ridgeway, London, GB
    Eur J Immunol 33:314-25. 2003
    ..Both of these Cre-transgenic lines will be useful in generating tissue-specific gene deletions within all the cells of hematopoietic or lymphoid tissues...
  13. ncbi Efficient recombination in diverse tissues by a tamoxifen-inducible form of Cre: a tool for temporally regulated gene activation/inactivation in the mouse
    Shigemi Hayashi
    Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA
    Dev Biol 244:305-18. 2002
    ..This inducible Cre system will be a broadly useful tool to modulate gene activity in mouse embryos, adults, and culture systems where temporal control is an important consideration...
  14. ncbi Faithful activation of an extra-bright red fluorescent protein in "knock-in" Cre-reporter mice ideally suited for lineage tracing studies
    Hervé Luche
    Institute of Immunology, University Clinics Ulm, Ulm, Germany
    Eur J Immunol 37:43-53. 2007
    ....
  15. ncbi A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration
    Thorsten Buch
    Laboratory for Molecular Immunology, Institute for Genetics, University of Cologne, D 50931 Cologne, Germany
    Nat Methods 2:419-26. 2005
    ..Notably, we show that the developing DT-specific antibody response is weak and not neutralizing, and thus does not impede the efficacy of DT. Our results validate the use of iDTR mice as a tool for cell ablation in vivo...
  16. ncbi Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knock-outs using Cre recombinase
    C Postic
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Biol Chem 274:305-15. 1999
    ..Interestingly, hepatic GK knock-out mice also have impaired insulin secretion in response to glucose. These studies indicate that deficiencies in both beta cell and hepatic GK contribute to the hyperglycemia of MODY-2...
  17. pmc A phage integrase directs efficient site-specific integration in human cells
    A C Groth
    Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305 5120, USA
    Proc Natl Acad Sci U S A 97:5995-6000. 2000
    ..These observations form the basis for site-specific integration strategies potentially useful in a broad range of genetic engineering applications...
  18. ncbi Talking about a revolution: The impact of site-specific recombinases on genetic analyses in mice
    Catherine S Branda
    Harvard Medical School, Department of Genetics, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Dev Cell 6:7-28. 2004
    ..By enabling high-fidelity DNA modifications to be induced in vitro or in vivo, these systems have incited a wave of new biology, advancing our understanding of gene function, genetic relationships, development, and disease...
  19. ncbi Mechanisms of site-specific recombination
    Nigel D F Grindley
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520 8114, USA
    Annu Rev Biochem 75:567-605. 2006
    ..Details of the site-specific recombination processes have been revealed by recent structural and biochemical studies of members of both families...
  20. ncbi Fate of the mammalian cardiac neural crest
    X Jiang
    Departments of Biological Sciences and Cell and Neurobiology, Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, IGM 240, Los Angeles, CA 90033, USA
    Development 127:1607-16. 2000
    ....
  21. ncbi Targeting Cre recombinase to specific neuron populations with bacterial artificial chromosome constructs
    Shiaoching Gong
    Gene Expression Nervous System Atlas Project, Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10021, USA
    J Neurosci 27:9817-23. 2007
  22. ncbi A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance
    J C Bruning
    Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Mol Cell 2:559-69. 1998
    ..Thus, insulin resistance in muscle contributes to the altered fat metabolism associated with type 2 diabetes, but tissues other than muscle appear to be more involved in insulin-regulated glucose disposal than previously recognized...
  23. pmc Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene
    N Harada
    Banyu Tsukuba Research Institute Merck, Tsukuba 300 2611, Japan
    EMBO J 18:5931-42. 1999
    ..Some nascent microadenomas were also found in the colon. These results present experimental genetic evidence that activation of the Wnt signaling pathway can cause intestinal and colonic tumors...
  24. ncbi Subregion- and cell type-restricted gene knockout in mouse brain
    J Z Tsien
    Howard Hughes Medical Institute, Center for Learning and Memory, Massachusetts Institute of Technology, Cambridge 02139, USA
    Cell 87:1317-26. 1996
    ..The brain subregional restricted gene knockout should allow a more precise analysis of the impact of a gene mutation on animal behaviors...
  25. pmc The mechanism of retroviral integration from X-ray structures of its key intermediates
    Goedele N Maertens
    Division of Infectious Diseases, Imperial College London, St Mary s Campus, Norfolk Place, London W2 1PG, UK
    Nature 468:326-9. 2010
    ..Our results resolve the structural basis for retroviral DNA integration and provide a framework for the design of INs with altered target sequences...
  26. pmc Site-specific genomic integration in mammalian cells mediated by phage phiC31 integrase
    B Thyagarajan
    Department of Genetics, Stanford University School of Medicine, Stanford, California 94305-5120
    Mol Cell Biol 21:3926-34. 2001
    ..This phage integrase-mediated reaction represents an effective site-specific integration system for higher cells and may be of value in gene therapy and other chromosome engineering strategies...
  27. pmc The magical touch: genome targeting in epidermal stem cells induced by tamoxifen application to mouse skin
    V Vasioukhin
    Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 96:8551-6. 1999
    ..These tools now pave the way for testing the functional role of different somatic mutations that may exist in mosaic disorders of the skin, including squamous and basal cell carcinomas...
  28. pmc Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras
    E L Jackson
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Genes Dev 15:3243-8. 2001
    ..Of particular significance, this system has led to the identification of a new cell type contributing to the development of pulmonary adenocarcinoma...
  29. ncbi Serine recombinases as tools for genome engineering
    William R A Brown
    School of Biology, Queens Medical Centre, Nottingham NG7 2UH, UK
    Methods 53:372-9. 2011
    ....
  30. pmc Growth inhibition and DNA damage induced by Cre recombinase in mammalian cells
    A Loonstra
    Division of Molecular Genetics and Center of Biomedical Genetics, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
    Proc Natl Acad Sci U S A 98:9209-14. 2001
    ..Prolonged, low levels of Cre activity permit recombination without concomitant toxicity. This urges for a careful titration of Cre activity in conditional gene modification in mammalian cells...
  31. ncbi Endogenous oncogenic K-ras(G12D) stimulates proliferation and widespread neoplastic and developmental defects
    David A Tuveson
    Abramson Family Cancer Research Institute, Abramson Cancer Center and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA
    Cancer Cell 5:375-87. 2004
    ..Our results suggest that endogenous oncogenic ras is sufficient to initiate transformation by stimulating proliferation, while further genetic lesions may be necessary for progression to frank malignancy...
  32. pmc Bromo- and extraterminal domain chromatin regulators serve as cofactors for murine leukemia virus integration
    Saumya Shree Gupta
    Institute of Virology, Hannover Medical School, Hannover, Germany
    J Virol 87:12721-36. 2013
    ..Our data suggest that BET proteins might act as chromatin-bound acceptors for the MLV preintegration complex. These results could pave a way to redirecting MLV DNA integration as a basis for creating safer retroviral vectors. ..
  33. pmc 3'-processing and strand transfer catalysed by retroviral integrase in crystallo
    Stephen Hare
    Division of Infectious Diseases, Imperial College London, London, UK
    EMBO J 31:3020-8. 2012
    ..The ground state structures moreover highlight a striking substrate mimicry utilized by the inhibitors in their binding to the IN active site and suggest ways to improve upon this clinically relevant class of small molecules...
  34. ncbi hGFAP-cre transgenic mice for manipulation of glial and neuronal function in vivo
    L Zhuo
    Department of Pathobiological Sciences, Waisman Center, University of Wisconsin, 1500 Highland Avenue, Madison, WI 53705 2280, USA
    Genesis 31:85-94. 2001
    ..Onset of Cre expression began in the forebrain by e13.5, suggesting that the hGFAP promoter is active in a multi-potential neural stem cell...
  35. pmc High-efficiency FLP and PhiC31 site-specific recombination in mammalian cells
    Christopher S Raymond
    Program in Developmental Biology, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
    PLoS ONE 2:e162. 2007
    ..Here we report the de novo synthesis of mouse codon-optimized FLP (FLPo) and PhiC31 (PhiC31o) SSRs, which result in recombination efficiencies similar to Cre...
  36. pmc Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma
    Andrew J Aguirre
    Department of Medical Oncology, Dana Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Genes Dev 17:3112-26. 2003
    ..This faithful mouse model may permit the systematic analysis of genetic lesions implicated in the human disease and serve as a platform for the identification of early disease markers and for the efficient testing of novel therapies...
  37. pmc Requirements for catalysis in the Cre recombinase active site
    Bryan Gibb
    Department of Biochemistry and Biophysics and Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Nucleic Acids Res 38:5817-32. 2010
    ..The results are discussed in the context of YR and TopIB structural models and data from related YR systems...
  38. pmc Conditional gene targeting in mouse pancreatic ß-Cells: analysis of ectopic Cre transgene expression in the brain
    Barton Wicksteed
    Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Chicago, Chicago, llinois, USA
    Diabetes 59:3090-8. 2010
    ..The objective of this study was to examine whether mouse transgenic Cre lines, used to mediate β-cell- or pancreas-specific recombination, also drive Cre expression in the brain...
  39. ncbi Identification of pseudo attP sites for phage phiC31 integrase in bovine genome
    Qing wen Ma
    Shanghai Institute of Medical Genetics, Shanghai Jiao Tong University, 24 1400 West Beijing Road, Shanghai 200040, PR China
    Biochem Biophys Res Commun 345:984-8. 2006
    ..Our study demonstrated that the phiC31 integrase system provides a new potential for genetic engineering of the bovine genome and might be beneficial for the research on ruminant...
  40. ncbi A practical summary of site-specific recombination, conditional mutagenesis, and tamoxifen induction of CreERT2
    Konstantinos Anastassiadis
    Center for Regenerative Therapy, Technische Universitaet Dresden, Dresden, Germany
    Methods Enzymol 477:109-23. 2010
    ..Recently a Cre-like recombinase, Dre has been added to the toolbox. Here, we summarize current knowledge about applications of Cre, Flp, and Dre in the mouse and present a protocol for tamoxifen induction of conditional mutagenesis...
  41. pmc Efficient site-specific integration in Plasmodium falciparum chromosomes mediated by mycobacteriophage Bxb1 integrase
    Louis J Nkrumah
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Nat Methods 3:615-21. 2006
    ..falciparum life cycle, and it illustrates the utility of Bxb1-based integrative recombination for genetic studies of intracellular eukaryotic organisms...
  42. ncbi Conditional control of gene expression in the mouse
    M Lewandoski
    Section of Genetics of Vertebrate Development, Laboratory of Cancer and Developmental Biology, National Cancer Institute Frederick Cancer Research and Development Center, Frederick, Maryland 21702 1201, USA
    Nat Rev Genet 2:743-55. 2001
    ..Here, I review these systems and discuss certain studies that exemplify the advantages and limitations of each system...
  43. pmc Notch-RBP-J signaling controls the homeostasis of CD8- dendritic cells in the spleen
    Michele L Caton
    Department of Microbiology, Columbia University Medical Center, New York, NY 10032, USA
    J Exp Med 204:1653-64. 2007
    ..Thus, canonical Notch-RBP-J signaling controls the maintenance of CD8(-) DCs in the splenic MZ, revealing an unexpected role of the Notch pathway in the innate immune system...
  44. ncbi The SOS response controls integron recombination
    Emilie Guerin
    Universite de Limoges, Faculte de Medecine, EA3175, INSERM, Equipe Avenir, 87000 Limoges, France
    Science 324:1034. 2009
    ..We found that LexA controlled expression of most integron integrases and consequently regulated cassette recombination...
  45. ncbi Vagaries of conditional gene targeting
    Marc Schmidt-Supprian
    Department of Pathology, Harvard Medical School and the CBR Institute for Biomedical Research, Boston, Massachusetts 02115, USA
    Nat Immunol 8:665-8. 2007
  46. ncbi Integration specificity of phage phiC31 integrase in the human genome
    Thomas W Chalberg
    Department of Genetics, Stanford University School of Medicine, Stanford, CA 95305 5120, USA
    J Mol Biol 357:28-48. 2006
    ..An analysis of the safety of integration sites in terms of proximity to cancer genes suggested minimal cancer risk. We conclude that integration systems derived from phiC31 integrase have great potential utility...
  47. ncbi Temporally regulated and tissue-specific gene manipulations in the adult and embryonic heart using a tamoxifen-inducible Cre protein
    D S Sohal
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Division of Molecular Cardiovascular Biology, Cincinnati, Ohio, USA
    Circ Res 89:20-5. 2001
    ....
  48. ncbi Conditional gene targeting in macrophages and granulocytes using LysMcre mice
    B E Clausen
    Institute for Genetics, University of Cologne, Germany
    Transgenic Res 8:265-77. 1999
    ..In contrast, no significant deletion was observed in tail DNA or purified T and B cells. Taken together, LysMcre mice allow for both specific and highly efficient Cre-mediated deletion of loxP-flanked target genes in myeloid cells...
  49. ncbi A reliable lacZ expression reporter cassette for multipurpose, knockout-first alleles
    Giuseppe Testa
    BIOTEC, Technische Universitat Dresden, c o Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Genesis 38:151-8. 2004
    ..Incorporation of site-specific recombination target sites creates a multipurpose allele for both knockout and conditional applications...
  50. ncbi Spatial and temporal expression of the Cre gene under the control of the MMTV-LTR in different lines of transgenic mice
    K U Wagner
    Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68198 6805, USA
    Transgenic Res 10:545-53. 2001
    ..Information provided by this study will guide the researcher to those cell types and developmental stages at which a phenotype can be expected upon deletion of relevant genes...
  51. pmc Retroviral DNA integration: viral and cellular determinants of target-site selection
    Mary K Lewinski
    Infectious Disease Laboratory, The Salk Institute, La Jolla, California, USA
    PLoS Pathog 2:e60. 2006
    ....
  52. pmc High efficiency site-specific genetic engineering of the mosquito genome
    D D Nimmo
    Centre for Applied Entomology and Parasitology, Keele University, Keele, Staffordshire UK
    Insect Mol Biol 15:129-36. 2006
    ..9-fold. The ability to efficiently target transgenes to specific chromosomal locations and the potential to integrate very large transgenes has broad applicability to research on many medically and economically important species...
  53. pmc A comparison of exogenous promoter activity at the ROSA26 locus using a ΦiC31 integrase mediated cassette exchange approach in mouse ES cells
    Chiann Mun Chen
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
    PLoS ONE 6:e23376. 2011
    ....
  54. ncbi HIV-1 proviral DNA excision using an evolved recombinase
    Indrani Sarkar
    Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D 01307 Dresden, Germany
    Science 316:1912-5. 2007
    ..Although a long way from use in the clinic, we speculate that this type of technology might be adapted in future antiretroviral therapies, among other possible uses...
  55. ncbi Targeting of cre to the Foxg1 (BF-1) locus mediates loxP recombination in the telencephalon and other developing head structures
    J M Hebert
    Department of Biological Sciences, Stanford University, Stanford, California, 94305 5020, USA
    Dev Biol 222:296-306. 2000
    ..Collectively, these data show that Foxg1-Cre mice should be useful in the deletion or ectopic expression of any floxed target gene in a Foxg1-like pattern...
  56. ncbi Stat3 activation is responsible for IL-6-dependent T cell proliferation through preventing apoptosis: generation and characterization of T cell-specific Stat3-deficient mice
    K Takeda
    Department of Biochemistry, Hyogo College of Medicine, Nishinomiya, Japan
    J Immunol 161:4652-60. 1998
    ..These results demonstrate that Stat3 activation is involved in IL-6-dependent T cell proliferation through prevention of apoptosis independently of Bcl-2...
  57. pmc High-resolution labeling and functional manipulation of specific neuron types in mouse brain by Cre-activated viral gene expression
    Sandra J Kuhlman
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America
    PLoS ONE 3:e2005. 2008
    ....
  58. ncbi Integration and excision by the large serine recombinase phiRv1 integrase
    Lori A Bibb
    Pittsburgh Bacteriophage Institute and Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Mol Microbiol 55:1896-910. 2005
    ..Although the mechanism of directional control of large serine integrases is poorly understood, a recombination directionality factor (RDF) has been identified that is required for ..
  59. ncbi Practical range of effective dose for Cre recombinase-expressing recombinant adenovirus without cell toxicity in mammalian cells
    Yasuko Baba
    Laboratory of Molecular Genetics, Institute of Medical Science, University of Tokyo, Japan
    Microbiol Immunol 49:559-70. 2005
    ..Cre-induced cell toxicity can be avoided by pre-examining the "effective range" using the purpose cell lines before starting experiments utilizing the experiment of Cre-expressing rAd...
  60. pmc Multiple new site-specific recombinases for use in manipulating animal genomes
    Aljoscha Nern
    Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147 2408, USA
    Proc Natl Acad Sci U S A 108:14198-203. 2011
    ..We also show that the KD and B3 recombinases are active in mice...
  61. pmc Molecular mechanisms of retroviral integrase inhibition and the evolution of viral resistance
    Stephen Hare
    Division of Infectious Diseases, Imperial College London, London W2 1PG, United Kingdom
    Proc Natl Acad Sci U S A 107:20057-62. 2010
    ..Furthermore, our structures predict physical proximity and an interaction between HIV-1 IN mutant residues His148 and Ser/Ala140, rationalizing the coevolution of Q148H and G140S/A mutations in drug-resistant viral strains...
  62. ncbi Phage integrases: biology and applications
    Amy C Groth
    Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305 5120, USA
    J Mol Biol 335:667-78. 2004
    Phage integrases are enzymes that mediate unidirectional site-specific recombination between two DNA recognition sequences, the phage attachment site, attP, and the bacterial attachment site, attB...
  63. pmc Functional and structural characterization of the integrase from the prototype foamy virus
    Eugene Valkov
    Division of Medicine, St Mary s Campus, Imperial College London, London, UK
    Nucleic Acids Res 37:243-55. 2009
    ....
  64. ncbi Generation of a prostate epithelial cell-specific Cre transgenic mouse model for tissue-specific gene ablation
    X Wu
    Department of Pathology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90089, USA
    Mech Dev 101:61-9. 2001
    ..The PB-Cre4 mice will be a useful resource for genetic-based studies on prostate development and prostatic disease...
  65. pmc Solution conformations of prototype foamy virus integrase and its stable synaptic complex with U5 viral DNA
    Kushol Gupta
    Department of Biochemistry and Biophysics, Perelman School of Medicine and Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104 6059, USA
    Structure 20:1918-28. 2012
    ..These results provide important insights into the architecture of the retroviral intasome...
  66. pmc A highly efficient ligand-regulated Cre recombinase mouse line shows that LoxP recombination is position dependent
    M Vooijs
    The Netherlands Cancer Institute, Division of Molecular Genetics, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    EMBO Rep 2:292-7. 2001
    ..This has important consequences when concurrent switching of multiple alleles within the same cell is needed, and highlights one of the difficulties that may be encountered when using reporter mice as indicator strains...
  67. ncbi Self-excising retroviral vectors encoding the Cre recombinase overcome Cre-mediated cellular toxicity
    D P Silver
    The Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 8:233-43. 2001
    ....
  68. ncbi Toxicity of ligand-dependent Cre recombinases and generation of a conditional Cre deleter mouse allowing mosaic recombination in peripheral tissues
    Dorothe Hameyer
    Institute of Toxicology Mouse Genetics, Johannes Gutenberg Universitat Mainz, Mainz, Germany
    Physiol Genomics 31:32-41. 2007
    ....
  69. ncbi Epiblast-restricted Cre expression in MORE mice: a tool to distinguish embryonic vs. extra-embryonic gene function
    M D Tallquist
    Program in Developmental Biology and Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Genesis 26:113-5. 2000
  70. ncbi A phage protein that binds φC31 integrase to switch its directionality
    Thanafez Khaleel
    Institute of Medical Sciences, Foresterhill, University of Aberdeen, Aberdeen AB25 2ZD, UK
    Mol Microbiol 80:1450-63. 2011
    ..b>Integrases usually require a recombination directionality factor (RDF) or Xis to control integration and excision and, as φ..
  71. ncbi Dre recombinase, like Cre, is a highly efficient site-specific recombinase in E. coli, mammalian cells and mice
    Konstantinos Anastassiadis
    Center for Regenerative Therapies Dresden, BioInnovationsZentrum Technische Universitaet Dresden, Am Tatzberg 47, 01307 Dresden, Germany
    Dis Model Mech 2:508-15. 2009
    ..Hence, we add another set of efficient tools to the genomic toolbox, which will enable the development of more sophisticated mouse models for the analysis of gene function and disease...
  72. ncbi A noninvasive genetic/pharmacologic strategy for visualizing cell morphology and clonal relationships in the mouse
    Tudor C Badea
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 23:2314-22. 2003
    ..Histochemical visualization of alkaline phosphatase activity reveals neuronal morphology with strong and uniform labeling of all processes...
  73. pmc Rapid generation of inducible mouse mutants
    Jost Seibler
    Artemis Pharmaceuticals GmbH, Neurather Ring 1, 51063 Cologne, Germany
    Nucleic Acids Res 31:e12. 2003
    ..Our findings provide a new concept allowing the generation of inducible mouse mutants within 6 months, as compared to 14 months using the current protocol...
  74. ncbi Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development
    V Brault
    Department of Molecular Embryology, Max Planck Institute of Immunobiology, Stuebeweg 51, D 79108 Freiburg, Germany
    Development 128:1253-64. 2001
    ..Our results demonstrate the pivotal role of beta-catenin in morphogenetic processes during brain and craniofacial development...
  75. ncbi Role of pathogenicity island-associated integrases in the genome plasticity of uropathogenic Escherichia coli strain 536
    Bianca Hochhut
    Institut für Molekulare Infektionsbiologie, Universitat Wurzburg, 97070 Wurzburg, Germany
    Mol Microbiol 61:584-95. 2006
    ..To investigate the role of PAI-encoded integrases for the recombination process the int genes of each unstable island of strain 536 were inactivated...
  76. ncbi Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery
    Angelo Lombardo
    San Raffaele Telethon Institute for Gene Therapy, Via Olgettina, 58, 20132 Milan, Italy
    Nat Biotechnol 25:1298-306. 2007
    ....
  77. pmc Conditional and inducible transgene expression in mice through the combinatorial use of Cre-mediated recombination and tetracycline induction
    Gusztav Belteki
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital 600 University Avenue, Toronto, Ontario, Canada M5G 1X5
    Nucleic Acids Res 33:e51. 2005
    ..The presented approach abrogates the need to generate tissue-specific rtTA transgenes for tissues where well-characterized Cre lines already exist...
  78. pmc Crystal structure of a wild-type Cre recombinase-loxP synapse reveals a novel spacer conformation suggesting an alternative mechanism for DNA cleavage activation
    Eric Ennifar
    Structural and Computational Biology Programme, EMBL, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Nucleic Acids Res 31:5449-60. 2003
    ..Our results also suggest that the Cre-induced kink next to the scissile phosphodiester activates the DNA for cleavage at this position and facilitates strand transfer...
  79. ncbi A distinctive class of integron in the Vibrio cholerae genome
    D Mazel
    Department of Microbiology and Immunology, University of British Columbia, 6174 University Boulevard, Vancouver, B C, V6T 1Z3, Canada
    Science 280:605-8. 1998
    ..VCR cassettes are found in a number of Vibrio species including a strain of V. metschnikovii isolated in 1888, suggesting that this mechanism of heterologous gene acquisition predated the antibiotic era...
  80. ncbi Good planning and serendipity: exploiting the Cre/Lox system in the testis
    Lee Smith
    MRC Human Reproductive Sciences Unit, The Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
    Reproduction 141:151-61. 2011
    ..This paper details the key considerations associated with exploitation of the Cre/Lox system and highlights a variety of validated Cre lines that have utility for conditional gene targeting within the testis...
  81. pmc Generation of a germ cell-specific mouse transgenic Cre line, Vasa-Cre
    Teresa Gallardo
    Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9072, USA
    Genesis 45:413-7. 2007
    ..This Vasa-Cre transgenic line should thus prove useful for genetic analysis of diverse aspects of gametogenesis and as a general deletor line...
  82. pmc Cre-lox-based system for multiple gene deletions and selectable-marker removal in Lactobacillus plantarum
    Jolanda M Lambert
    Wegeningen Centre for Food Science, Microbial Functionality and Safety Programme, Health and Safety Department, P O Box 20, 6710 BA Ede, The Netherlands
    Appl Environ Microbiol 73:1126-35. 2007
    ..The fact that 99.4% of the clones that were analyzed had undergone correct Cre-lox resolution emphasizes the suitability of the system described here for multiple gene replacement and deletion strategies in a single genetic background...
  83. pmc Successive and targeted DNA integrations in the Drosophila genome by Bxb1 and phiC31 integrases
    Juan Huang
    Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Genetics 189:391-5. 2011
    ..By alternately using Bxb1 and ϕC31, we were able to carry out multiple rounds of successive and targeted DNA integrations in our genomic engineering founder lines for the purpose of generating complex knock-in alleles...
  84. ncbi Cre activity causes widespread apoptosis and lethal anemia during embryonic development
    L A Naiche
    Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Genesis 45:768-75. 2007
    ..This information will be critical in both evaluating previously published work using cre alleles and in designing future experiments...
  85. pmc Split-cre complementation indicates coincident activity of different genes in vivo
    Johannes Hirrlinger
    Faculty of Medicine, Interdisciplinary Centre for Clinical Research, IZKF, University of Leipzig, Leipzig, Germany
    PLoS ONE 4:e4286. 2009
    ..Thus, split-Cre mediated genomic recombination constitutes a powerful spatial and temporal coincidence detector for in vivo targeting...
  86. pmc Estrogen receptor-alpha expression in the mammary epithelium is required for ductal and alveolar morphogenesis in mice
    Yuxin Feng
    Department of Cell and Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
    Proc Natl Acad Sci U S A 104:14718-23. 2007
    ..These observations suggest that ERalpha expression in the mammary epithelium is essential for normal ductal morphogenesis during puberty and alveologenesis during pregnancy and lactation...
  87. ncbi Integrons: agents of bacterial evolution
    Didier Mazel
    Unité Plasticité du Génome Bactérien CNRS URA 2171, Department Génomes et Génétique, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris, France
    Nat Rev Microbiol 4:608-20. 2006
    ..Here, the basic biology of integrons and superintegrons, their evolutionary history and the evidence for the existence of a novel recombination pathway is reviewed...
  88. pmc Site-specific transformation of Drosophila via phiC31 integrase-mediated cassette exchange
    Jack R Bateman
    Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genetics 173:769-77. 2006
    ..Thus, C31 integrase-mediated RMCE should greatly facilitate transgene analysis as well as permit new experimental designs...
  89. ncbi Rx-Cre, a tool for inactivation of gene expression in the developing retina
    Eric C Swindell
    Genesis 44:361-3. 2006
    ..Using these sequences, we made a Cre line that can be used for inactivation of gene expression in the developing retina...
  90. ncbi Binding and stimulation of HIV-1 integrase by a human homolog of yeast transcription factor SNF5
    G V Kalpana
    Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, College of Physicians and Surgeons, New York, NY 10032
    Science 266:2002-6. 1994
    ..The gene, termed INI1 (for integrase interactor 1), may encode a nuclear factor that promotes integration and targets incoming viral DNA to active genes...
  91. ncbi A novel transgenic technique that allows specific marking of the neural crest cell lineage in mice
    Y Yamauchi
    Institute of Molecular Embryology and Genetics, Center for Animal Resources and Development, Kumamoto University School of Medicine, 4 24 1 Kuhonji, Kumamoto, 862 0976, Japan
    Dev Biol 212:191-203. 1999
    ..We believe that P0-Cre transgenic mice will facilitate many interesting experiments, including lineage analysis, purification, and genetic manipulation of the mammalian neural crest cells...
  92. ncbi Integrase-defective lentiviral vectors: progress and applications
    M B Banasik
    Department of Pediatrics, Program in Gene Therapy, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
    Gene Ther 17:150-7. 2010
    ..Several recent publications outline the development and initial biological characterization of such vectors. Here, we discuss the potential applications and new directions for the development of integration-defective LVs...
  93. ncbi DNA topology and geometry in Flp and Cre recombination
    Alexandre A Vetcher
    Institute of Biomedical Sciences and Technology and Department of Molecular and Cell Biology, The University of Texas at Dallas, Richardson, TX 75083, USA
    J Mol Biol 357:1089-104. 2006
    ..Only modest conformational changes within this structure are needed to form the symmetric, planar DNA junction, which may be characteristic of shorter-lived intermediates along the recombination pathway...
  94. ncbi Presence and distribution of neural crest-derived cells in the murine developing thymus and their potential for differentiation
    Hidetoshi Yamazaki
    Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science, Yonago 683 8503, Japan
    Int Immunol 17:549-58. 2005
    ....
  95. ncbi Novel integrase-defective lentiviral episomal vectors for gene transfer
    J Vargas
    Division of Infectious Disease, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA
    Hum Gene Ther 15:361-72. 2004
    ..Lentiviral episomal vectors may serve as specific tools for therapeutic approaches to diseases, particularly those associated with episomal replication of DNA viruses including papillomaviruses, polyomaviruses, and herpesviruses...
  96. ncbi Temporal control of neural crest lineage generation by Wnt/β-catenin signaling
    Lisette Hari
    Cell and Developmental Biology, Institute of Anatomy, University of Zurich, CH 8057 Zurich, Switzerland
    Development 139:2107-17. 2012
    ..Thus, neural crest cells appear to be multipotent in vivo both before and after emigration from the neural tube but adapt their response to extracellular signals in a temporally controlled manner...
  97. ncbi Archaeal integrases and mechanisms of gene capture
    Q She
    Danish Archaea Centre, Institute of Molecular Biology, Copenhagen University, Sølvgade 83H, DK 1307 Copenhagen K, Denmark
    Biochem Soc Trans 32:222-6. 2004
    Archaeal integrases facilitate the formation of two distinctive types of integrated element within archaeal chromosomes: the SSV type and pNOB8 type...
  98. pmc Non-β-cell progenitors of β-cells in pregnant mice
    Sylvie Abouna
    Department of Biological Sciences, University of Warwick, Coventry, UK
    Organogenesis 6:125-33. 2010
    ..Further, there was no transdifferentiation of β-cells to other cell types in a two and half month period following labeling, including the period of pregnancy...
  99. pmc Inverse correlation between promoter strength and excision activity in class 1 integrons
    Thomas Jové
    Universite de Limoges, Faculte de Medecine, EA3175, Limoges, France
    PLoS Genet 6:e1000793. 2010
    ..There are five main Pc-P2 combinations, corresponding to five promoter strengths, and three main integrases displaying similar integration activity but very different excision efficiency...
  100. pmc Susceptible stages in Schwann cells for NF1-associated plexiform neurofibroma development
    Lu Q Le
    Departments of Developmental Biology and Dermatology, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 9133, USA
    Cancer Res 71:4686-95. 2011
    ..This model has important implications for understanding early cellular events that dictate neurofibroma development, as well as for the development of novel therapies targeting these tumors...
  101. ncbi Direct hematological toxicity and illegitimate chromosomal recombination caused by the systemic activation of CreERT2
    Atsuko Yoshioka Higashi
    Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    J Immunol 182:5633-40. 2009
    ..We discussed how to avoid the misinterpretation of the experimental results from potential toxic effects due to the activated CreER(T2)...

Research Grants64

  1. Integration and Excision by Serine Intergrases
    Graham F Hatfull; Fiscal Year: 2013
    ..analysis shows that their mechanism is distinctly different to the well-characterized tyrosine-recombinase integrases. More specifically, the Bxb1 integrase acts to recombine two DNA sites - attB and attP - that are small (<..
  2. CODA Assembly of Mutant Genes
    SHE PIN contact HUNG; Fiscal Year: 2010
    ..is an important retroviral drug target and its understanding is a major medical goal: (1) to find active soluble integrases (IN) for HIV and Ty3 that might lead to crystal structure(s) of active IN(s);(2) to understand the structural ..
  3. Crystallographic Studies of Retroviral Integrases
    Hideki Aihara; Fiscal Year: 2013
    ..During the initial 2-year R21 (ARRA) phase, we will focus on the structure determination of an intact 3-domain IN as proposed in our aim1. ..
  4. Crystallographic Studies of Retroviral Integrases
    Hideki Aihara; Fiscal Year: 2010
    ..During the initial 2-year R21 (ARRA) phase, we will focus on the structure determination of an intact 3-domain IN as proposed in our aim1. ..
  5. Structural understanding of Mu transposition
    Phoebe A Rice; Fiscal Year: 2013
    ..is the most thoroughly characterized of the large and highly diverse "DDE" family of transposases and retroviral integrases, and studies of Mu will continue to illuminate paradigms that translate to the rest of the family...
  6. Structure/Function Analysis of the Retrovirus Integrase
    JONATHAN P LEIS; Fiscal Year: 2010
    ..by applicant): This is a proposal to carry out a structure/function comparison of two different retrovirus integrases (INs) that highlight both similarities and differences in their respective viral and target DNA binding sites...
  7. SUBSTRATE INTERACTIONS OF A MULTIFUNCTIONAL INTEGRASE
    Michael Katzman; Fiscal Year: 2000
    ..2) Understand how integrase interacts with its target DNA substrates. Assays of new chimeric integrases will localize the viral DNA site (which is hypothesized to be in the C-terminal portion of the central domain) ..
  8. Phenotypes of HIV-1 Integrases
    William Robinson; Fiscal Year: 2009
    ..Inhibitors of integrase are in clinical testing. Understanding how HIV becomes resistant to these compounds and how such compounds interact with integrase are fundamental to the synthesis of better anti-HIV drugs. ..
  9. Targeted Transgene Integration through Chromatin tethering for Globin Gene Therap
    ANDRE MICHAEL LIEBER; Fiscal Year: 2010
    ..for improving targeted integration of existing retrovirus vectors through chromatin tethering of retroviral integrases. PUBLIC HEALTH RELEVANCE: We propose a novel vector system to achieve targeted integration of a large transgene ..
  10. IMPROVED ADENOVIRAL VECTORS FOR HEPATIC GENE THERAPY
    Mark Kay; Fiscal Year: 2006
    ..Using DNA transposons and site-specific phage integrases, we plan to develop gone-deleted vectors that can integrate an expression cassette into the host chromosome...
  11. MODIFYING HIV TO INTEGRATE AT PRESELECTED DNA SITES
    Frederic Bushman; Fiscal Year: 2000
    ..More recently they have found that i) they can create biologically active HIV proviruses encoding integrases fused to DNA-binding domains, and ii) preintegration complexes containing such fusions direct integration ..
  12. Growth, Differentiation and Genetic Alteration of Human ES Cells
    Gordon Keller; Fiscal Year: 2007
    ..genetic modification of the hES cells, through the use of adeno-associated viruses (AAV) and bacteriophage integrases, respectively...
  13. Inhibitors of pox virus Holliday juction resolvase
    Anca Segall; Fiscal Year: 2005
    ....
  14. Novel antibiotics that trap Holliday junctions
    Anca Segall; Fiscal Year: 2008
    ..6) Investigate the effect of the peptides on Salmonella and Staph infections in mice in two well-studied infectious disease model systems. ..
  15. LEDGF-Integrase Structural Biology
    Alan Engelman; Fiscal Year: 2005
    ..abstract_text> ..
  16. BIOCHEMICAL MECHANISM OF HIV DNA INTEGRATION
    Alan Engelman; Fiscal Year: 2009
    ..abstract_text> ..
  17. MECHANISM OF NON-INTEGRASE-MEDIATED HIV-1 REPLICATION
    Alan Engelman; Fiscal Year: 2001
    ..Further aims are to develop gene therapy vectors based on non-integrating retroviruses. ..
  18. Pathways fo Lambda Site-Specific Recombination
    ANCA MARA SEGALL; Fiscal Year: 2010
    ..The new characterization will include structural studies of the inhibitors. ..
  19. Molecular Genetics of Cadmium Toxicity
    Daniel W Nebert; Fiscal Year: 2010
    ....
  20. Retinal Gene Therapy by Site-Specific Integration
    MICHELE CALOS; Fiscal Year: 2006
    ..These experiments will move the phiC31 integrase [unreadable] [unreadable] [unreadable]..
  21. PAHs: Balance of Detoxication vs Metabolic Activation
    Daniel Nebert; Fiscal Year: 2009
    ..dissemination of ingested BaP and will be informative in clinical studies in which we would determine which haplotypes of these three human genes might be associated with resistance vs. sensitivity to PAH-induced toxicity and cancer. ..
  22. STEREOCHEMISTRY OF SITE SPECIFIC RECOMBINATION
    GREGORY VAN DUYNE; Fiscal Year: 2006
    ..abstract_text> ..
  23. STRUCTURE AND REGULATION OF PROTEIN/DNA ASSEMBLIES
    GREGORY VAN DUYNE; Fiscal Year: 2002
    ....
  24. SITE-SPECIFIC INTEGRATION FOR GENE THERAPY
    MICHELE CALOS; Fiscal Year: 2003
    ..The novel site-specific integration strategy developed here can be used to add value to most current gene therapy vectors. ..
  25. GENOTOXICITY IN CYP1A2 DEFICIENT TRANSGENIC MICE
    Daniel Nebert; Fiscal Year: 2002
    ..S. population. ..
  26. CYP1A1 GENE AND ENVIRONMENTAL TOXICITY
    Daniel Nebert; Fiscal Year: 2005
    ..abstract_text> ..
  27. Transferring integrase technology to animals
    MICHELE CALOS; Fiscal Year: 2006
    ..By scaling up to animals more similar to humans, these experiments will move the site-specific integrase technology closer to the clinic. [unreadable] [unreadable] [unreadable]..
  28. Custom integration tools for functional genomics
    MICHELE CALOS; Fiscal Year: 2003
    ..The work elaborates on a successful line of research in my laboratory involving recombination mediated by phage integrases at their compact (30 - 40-bp) attB and attP recognition sites...
  29. MUTAGENESIS PERMITTING CONTROLLED GENE EXPRESSION
    Xiaoxi Zhuang; Fiscal Year: 2003
    ..They will provide valuable resources to the scientific community for the study of gene function in vivo. ..
  30. K12 Expression: Cornea-Type Epithelial Differentiation
    WINSTON KAO; Fiscal Year: 2008
    ..Aim 3 is to examine roles of Fos on corneal-type epithelium differentiation and corneal wound healing as described in Aim 2. ..
  31. New Insights into Animals Models of Diabetes
    Edward Leiter; Fiscal Year: 2003
    ..The meeting is planned for 200 participants. Because of limited seating capacity in The Jackson Laboratory's auditorium, the meeting venue will be the Bar Harbor Regency Hotel, where participants will be housed and fed. ..
  32. Mechanism of Redox Regulation by Ape1/Ref-1
    Millie M Georgiadis; Fiscal Year: 2010
    ..We propose here to elucidate the mechanism of the redox function of Ape1 and explore its role in tumor cell response following treatment with DNA damaging agents. ..
  33. ANALYSIS OF BIDIRECTIONAL SIGNALING MECHANISMS FOR BTLA AND HVEM IN AUTOIMMUNITY
    Kenneth M Murphy; Fiscal Year: 2010
    ..Importantly, BTLA has recently been reported to be involved in the susceptibility in humans to rheumatoid arthritis. Thus, our proposed studies into this newly identified but poorly understood molecule are particularly timely. ..
  34. GLUCOKINASE GENE EXPRESSION IN PANCREATIC BETA CELL
    Mark Magnuson; Fiscal Year: 2005
    ..In Aim 3 we will determine the role of alternate RNA processing the insulin receptor in modulating both GK gene transcription and subcellular localization in the pancreatic beta cell. ..
  35. EPIGENETIC CHANGES IN FRONTAL LOBE OF SCHIZOPHRENICS
    Schahram Akbarian; Fiscal Year: 2009
    ....
  36. Design of Genetically Encoded Ca2+ Indicators for in Vivo Application
    Michael I Kotlikoff; Fiscal Year: 2010
    ..The proposal will produce novel proteins that will track the function of cells at the molecular level. ..
  37. INTEGRATION AND EXCISION OF PROPHAGES IN TUBERCULOSIS
    Graham Hatfull; Fiscal Year: 2003
    ..tuberculoses to determine whether they have functional recombination systems; whether they act as Genetic Transfer Agents; and whether they play a role in virulence of M. tuberculosis. ..
  38. Purchase of Transmission Electron Microscope (TEM)
    Michael Cox; Fiscal Year: 2003
    ..In addition, its operation will be integrated with that of the two other electron microscopes on campus (of more recent vintage), which are located in the veterinary and medical schools. ..
  39. MECHANISM OF PHAGE L5 INTEGRATION AND EXCISION
    Graham Hatfull; Fiscal Year: 2002
    ..In addition to Providing new insights into the mechanism of recombination these studies will offer new tools for mycobacterial genetics and a greater understanding of mycobacterial physiology. ..
  40. NEW MOUSE MODELS OF DIABESITY
    Edward Leiter; Fiscal Year: 2002
    ..Collectively, these studies will permit genetic and metabolic characterization of key events in the transition from simple obesity to diabesity in thee novel mouse models. ..
  41. Stromal Contributions of Adipocytes in Breast Cancer
    Philipp Scherer; Fiscal Year: 2009
    ..These studies will help define the role of mammary adipocytes in the pathogenesis of breast cancer. ..
  42. Role of ALK3 in atrioventricular valve development
    Vinciane Gaussin; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  43. MECHANISMS FOR CHEMOPREVENTION OF COLON CANCER
    CHINTHALAPALLY RAO; Fiscal Year: 2004
    ..Tissue distribution and comparative metabolism studies of curcumin and PEMC will be studied with synthetic [3H] curcumin and [3H]-PEMC in vivo in male F-344 rats. ..
  44. MECHANISM OF HIV DNA INTEGRATION
    Frederic Bushman; Fiscal Year: 2005
    ..Long term, these studies, together with data on protein structures, will provide a high-resolution picture of the organization and function of preintegration complexes. ..
  45. Role of SLP-76 in Naive and Memory T Cell Function
    JONATHAN MALTZMAN; Fiscal Year: 2006
    ..In addition to Dr. Koretzky, an advisory committee of physician-scientists has been formed to oversee scientific and career development. [unreadable] [unreadable]..
  46. MECHANISM OF INSERTION SEQUENCE TRANSLOCATION
    NIGEL GRINDLEY; Fiscal Year: 2005
    ..We intend to focus on the role of the accessory transposition protein, TnpB in activation of TnpA (allowing it to cleave uncleaved transposon ends) and in transposition immunity. ..
  47. Chromatin Pathology in Cerebral Cortex of Schizophrenics
    Schahram Akbarian; Fiscal Year: 2006
    ..Finally, the proposed studies will provide the framework for future proposals designed to map histone modification patterns across entire chromosomes in human brain, including alterations in major psychiatric disease. ..
  48. HPV in Differentiated Human Airway Epithelia In Vitro
    John Lee; Fiscal Year: 2006
    ..These studies will provide new insight into HPV-related airway disease and should hasten the development of new treatments. ..
  49. 2003 Genetic Toxicology Gordon Conference
    Anthony Carr; Fiscal Year: 2007
    ..We particularly air to obtain funding to support applications from minority groupings and younger scientists. We have already identified a significant participation of women amongst our list of speakers. ..
  50. SACRAL CREST CELLS AND ENTERIC NEURODEVELOPMENT
    Raj Kapur; Fiscal Year: 2005
    ..The results of this study will further our understanding of normal enteric neurodevelopment and congenital disorders of intestinal motility. ..
  51. Conditional Deletion of Dnaic1 as a Model of Primary Ciliary Dyskinesia
    LAWRENCE OSTROWSKI; Fiscal Year: 2007
    ..If successful, this model will also provide a novel system to investigate other questions concerning pulmonary health and disease. [unreadable] [unreadable] [unreadable]..
  52. The role of EGFR signaling in progression of Kras-induced pacreatic tumors
    Anna Means; Fiscal Year: 2007
    ..The studies proposed here investigate EGFR signaling as a potential biomarker and/or therapeutic target, by studying its effects on tumorigenesis in a mouse model of pancreatic cancer. [unreadable] [unreadable] [unreadable]..
  53. Recombinant FIV vectors for the delivery of siRNA therapy to joints
    Stephanos Kyrkanides; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  54. FATE MAPS OF EMBRYONIC GENE EXPRESSION IN MICE
    STEPHEN O GORMAN; Fiscal Year: 2004
    ....
  55. PREVENTION OF COLORECTAL CANCER BY iNOS AND COX-2 SELECTIVE INHIBITORS
    CHINTHALAPALLY RAO; Fiscal Year: 2008
    ..abstract_text> ..
  56. TMRNA AND TRANS TRANSLATION--MECHANISM AND BIOLOGY
    Kelly Williams; Fiscal Year: 2003
    ..5) Analyze structure of tmRNA alone and in trans-translation complexes by chemical probing, cross-linking, crystallographic, and electron micrographic (the latter two collaborative) approaches. ..
  57. Adiponectin: Effects on Graves' Optalmopathy
    Philipp Scherer; Fiscal Year: 2005
    ....
  58. Adipogenesis, Obesity and Inflammation
    Philipp Scherer; Fiscal Year: 2005
    ..Some sessions will be held jointly with the "Diabetes Mellitus and the control of Cellular Energy Metabolism" meeting that will effectively complement the obesity meeting. ..
  59. Web-Based System for Research Protocol Submission
    Roberto Gomez; Fiscal Year: 2003
    ..We will try to reach small institutions by annoucements and demonstrations at local, regional and national meetings of the Society for Research Administration, International. ..