lethal genes


Summary: Genes which result in the premature death of the organism; dominant lethal genes kill heterozygotes, whereas recessive lethal genes kill only homozygotes.

Top Publications

  1. ncbi Gene mapping within the T/t complex of the mouse. I. t-Lethal genes are nonallelic
    K Artzt
    Cell 28:463-70. 1982
  2. ncbi Exploring genetic interactions and networks with yeast
    Charles Boone
    Banting and Best Department of Medical Research and Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto M5S 3E1, Canada
    Nat Rev Genet 8:437-49. 2007
  3. ncbi MEX-3 is a KH domain protein that regulates blastomere identity in early C. elegans embryos
    B W Draper
    Department of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Cell 87:205-16. 1996
  4. pmc Targeted disruption of fibroblast growth factor (FGF) receptor 2 suggests a role for FGF signaling in pregastrulation mammalian development
    E Arman
    Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel 76100, USA
    Proc Natl Acad Sci U S A 95:5082-7. 1998
  5. ncbi The concept of synthetic lethality in the context of anticancer therapy
    William G Kaelin
    Howard Hughes Medical Institute, 44 Binney Street, Mayer 457, Boston, Massachusetts 02115, USA
    Nat Rev Cancer 5:689-98. 2005
  6. ncbi Adaptive evolution drives divergence of a hybrid inviability gene between two species of Drosophila
    Daven C Presgraves
    Department of Biology, University of Rochester, Rochester, New York 14627, USA
    Nature 423:715-9. 2003
  7. ncbi Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice
    F Shalaby
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Nature 376:62-6. 1995
  8. pmc Quasispecies made simple
    J J Bull
    Institute for Cellular and Molecular Biology, Section of Integrative Biology, University of Texas, Austin, Texas, United States of America
    PLoS Comput Biol 1:e61. 2005
  9. ncbi Cardiomyopathy in zebrafish due to mutation in an alternatively spliced exon of titin
    Xiaolei Xu
    Cardiovascular Research Center, Massachusetts General Hospital, 149 13th Street, Charlestown, Massachusetts 02129, USA
    Nat Genet 30:205-9. 2002
  10. ncbi Epithelial detachment due to absence of hemidesmosomes in integrin beta 4 null mice
    R van der Neut
    Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Nat Genet 13:366-9. 1996

Detail Information

Publications231 found, 100 shown here

  1. ncbi Gene mapping within the T/t complex of the mouse. I. t-Lethal genes are nonallelic
    K Artzt
    Cell 28:463-70. 1982
    ..In all cases these lethal mutations were nonallelic to tw12. These results, together with evidence for functional relatedness, suggest the t-lethals may be a gene family spread out over more than 15 centiMorgans of chromosome 17...
  2. ncbi Exploring genetic interactions and networks with yeast
    Charles Boone
    Banting and Best Department of Medical Research and Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto M5S 3E1, Canada
    Nat Rev Genet 8:437-49. 2007
    ..A comparative understanding of genetic-interaction networks promises insights into some long-standing genetic problems, such as the nature of quantitative traits and the basis of complex inherited disease...
  3. ncbi MEX-3 is a KH domain protein that regulates blastomere identity in early C. elegans embryos
    B W Draper
    Department of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Cell 87:205-16. 1996
    ..We propose that MEX-3 contributes to anterior-posterior asymmetry by regulating one or more mRNAs involved in specifying the fate of the posterior blastomere...
  4. pmc Targeted disruption of fibroblast growth factor (FGF) receptor 2 suggests a role for FGF signaling in pregastrulation mammalian development
    E Arman
    Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel 76100, USA
    Proc Natl Acad Sci U S A 95:5082-7. 1998
    ..The role of early FGF signaling in pregastrulation development as a possible adaptation to mammalian (amniote) embryogenesis is discussed...
  5. ncbi The concept of synthetic lethality in the context of anticancer therapy
    William G Kaelin
    Howard Hughes Medical Institute, 44 Binney Street, Mayer 457, Boston, Massachusetts 02115, USA
    Nat Rev Cancer 5:689-98. 2005
    ..not been exploited in the past because there were no robust methods for systematically identifying synthetic lethal genes. This is changing as a result of the increased availability of chemical and genetic tools for perturbing gene ..
  6. ncbi Adaptive evolution drives divergence of a hybrid inviability gene between two species of Drosophila
    Daven C Presgraves
    Department of Biology, University of Rochester, Rochester, New York 14627, USA
    Nature 423:715-9. 2003
    ..These results show that a lethal hybrid incompatibility has evolved as a by-product of adaptive protein evolution...
  7. ncbi Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice
    F Shalaby
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Nature 376:62-6. 1995
    ..These results indicate that Flk-1 is essential for yolk-sac blood-island formation and vasculogenesis in the mouse embryo...
  8. pmc Quasispecies made simple
    J J Bull
    Institute for Cellular and Molecular Biology, Section of Integrative Biology, University of Texas, Austin, Texas, United States of America
    PLoS Comput Biol 1:e61. 2005
    ..Based on this framework, we argue that the lethal mutagenesis of a viral infection by mutation-inducing drugs is not a true error catastophe, but is an extinction catastrophe...
  9. ncbi Cardiomyopathy in zebrafish due to mutation in an alternatively spliced exon of titin
    Xiaolei Xu
    Cardiovascular Research Center, Massachusetts General Hospital, 149 13th Street, Charlestown, Massachusetts 02129, USA
    Nat Genet 30:205-9. 2002
    ..Absence of Titin function thus results in blockage of sarcomere assembly and causes a functional disorder resembling human dilated cardiomyopathies, one form of which is described in another paper in this issue...
  10. ncbi Epithelial detachment due to absence of hemidesmosomes in integrin beta 4 null mice
    R van der Neut
    Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Nat Genet 13:366-9. 1996
    ..No evidence was found for impaired T-cell development, nor for defects in myelination in the peripheral nervous system...
  11. pmc Significant conservation of synthetic lethal genetic interaction networks between distantly related eukaryotes
    Scott J Dixon
    Banting and Best Department of Medical Research and Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Room 1330, Toronto, ON, Canada M5S 3E1
    Proc Natl Acad Sci U S A 105:16653-8. 2008
    ..We define a conserved yeast network (CYN) composed of 106 genes and 144 interactions and suggest that this network may help understand the shared biology of diverse eukaryotic species...
  12. ncbi Gamma-tubulin is a component of the spindle pole body that is essential for microtubule function in Aspergillus nidulans
    B R Oakley
    Department of Molecular Genetics, Ohio State University, Colombus 43210
    Cell 61:1289-301. 1990
    ..We propose that gamma-tubulin attaches microtubules to the spindle pole body, nucleates microtubule assembly, and establishes microtubule polarity in vivo...
  13. ncbi Targeted mutation of the DNA methyltransferase gene results in embryonic lethality
    E Li
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142
    Cell 69:915-26. 1992
  14. ncbi Synthetic lethal screen identification of chemosensitizer loci in cancer cells
    Angelique W Whitehurst
    Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Nature 446:815-9. 2007
  15. pmc Hybrid lethal systems in the Drosophila melanogaster species complex. II. The Zygotic hybrid rescue (Zhr) gene of D. melanogaster
    K Sawamura
    Department of Genetics, Graduate University for Advanced Studies, National Institute of Genetics, Shizuoka, Japan
    Genetics 133:307-13. 1993
    ..A model is proposed to explain the genetic mechanisms of hybrid lethalities as well as the evolutionary pathways...
  16. ncbi The tumor suppressor gene Brca1 is required for embryonic cellular proliferation in the mouse
    R Hakem
    Amgen Institute, Toronto, Ontario, Canada
    Cell 85:1009-23. 1996
    ..Thus, the death of Brca1(5-6) mutant embryos prior to gastrulation may be due to a failure of the proliferative burst required for the development of the different germ layers...
  17. pmc Targeted disruption of gp130, a common signal transducer for the interleukin 6 family of cytokines, leads to myocardial and hematological disorders
    K Yoshida
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    Proc Natl Acad Sci U S A 93:407-11. 1996
    ..Some gp130-/- embryos show anemia due to impaired development of erythroid lineage cells. These results indicate that gp130 plays a crucial role in myocardial development and hematopoiesis during embryogenesis...
  18. ncbi Paralysis and early death in cysteine string protein mutants of Drosophila
    K E Zinsmaier
    California Institute of Technology, Division of Biology, Pasadena 91125
    Science 263:977-80. 1994
    ..Deletion of the csp gene in Drosophila causes a temperature-sensitive block of synaptic transmission, followed by paralysis and premature death...
  19. pmc The product of the spindle formation gene sad1+ associates with the fission yeast spindle pole body and is essential for viability
    I Hagan
    Department of Biophysics, Faculty of Science, Kyoto University, Japan
    J Cell Biol 129:1033-47. 1995
    ..Sad1 may play a role in SPB structure, such as maintaining a functional interface with the nuclear membrane or in providing an anchor for the attachment of microtubule motor proteins...
  20. ncbi Disruption of the single tropomyosin gene in yeast results in the disappearance of actin cables from the cytoskeleton
    H P Liu
    Section on Biochemistry Molecular, Cornell University, Ithaca, New York 14853
    Cell 57:233-42. 1989
    ..These results strongly suggest that tropomyosin interacts with F actin in vivo and may play an important role in assembling or stabilizing actin cables in yeast...
  21. pmc Systematic yeast synthetic lethal and synthetic dosage lethal screens identify genes required for chromosome segregation
    Vivien Measday
    Wine Research Centre and Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada V6T 1Z4
    Proc Natl Acad Sci U S A 102:13956-61. 2005
    ..Our study shows that systematic genetic screens are a powerful means to discover roles for uncharacterized genes and genes with alternative functions in chromosome maintenance that may not be discovered by using proteomics approaches...
  22. pmc Multiple genetic pathways for restarting DNA replication forks in Escherichia coli K-12
    S J Sandler
    Department of Microbiology, University of Massachusetts, Amherst 01003, USA
    Genetics 155:487-97. 2000
    ..It is further hypothesized that the dnaC809 suppression of priA2::kan requires priC and rep, whereas dnaC809,820 suppression of priA2::kan does not...
  23. pmc Segmental aneuploidy and the genetic gross structure of the Drosophila genome
    D L Lindsley
    Genetics 71:157-84. 1972
    ..Moreover, except for the single triplo-lethal locus, the effects of hyperploidy are much less pronounced than those of the corresponding hypoploidy...
  24. ncbi Targeted disruption of mouse conventional kinesin heavy chain, kif5B, results in abnormal perinuclear clustering of mitochondria
    Y Tanaka
    Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Hongo, Japan
    Cell 93:1147-58. 1998
    ..These data collectively indicate that kinesin is essential for mitochondrial and lysosomal dispersion rather than for the Golgi-to-ER traffic in these cells...
  25. pmc Construction, characterization, and complementation of a conditional-lethal DNA topoisomerase IIalpha mutant human cell line
    Adam J Carpenter
    Gene Targeting Group, Medical Research Council Clinical Sciences Centre, Imperial College Faculty of Medicine, Hammersmith Hospital Campus, London W12 ONN, United Kingdom
    Mol Biol Cell 15:5700-11. 2004
  26. ncbi The Drosophila gene hid is a direct molecular target of Ras-dependent survival signaling
    A Bergmann
    Massachusetts Institute of Technology, Howard Hughes Medical Institute, Department of Biology, Cambridge 02139, USA
    Cell 95:331-41. 1998
    ..These findings define a novel mechanism by which growth factor signaling directly inactivates a critical component of the intrinsic cell death machinery. These studies provide further insights into the function of ras as an oncogene...
  27. ncbi Homologous recombination is responsible for cell death in the absence of the Sgs1 and Srs2 helicases
    S Gangloff
    CEA de Fontenay aux Roses, UMR 217 CNRS CEA DSV DRR LERA, 92265 Fontenay aux Roses, France
    Nat Genet 25:192-4. 2000
    ..Yeast SRS2 encodes another DNA helicase involved in the maintenance of genome integrity. Our data suggest that some defects observed in BS, WS or RTS are the consequence of unrestrained recombination...
  28. ncbi Large-scale identification of essential Salmonella genes by trapping lethal insertions
    Karin Knuth
    CREATOGEN AG, Ulmer Str 160a, D 86156 Augsburg, Germany
    Mol Microbiol 51:1729-44. 2004
    ..The results of this large-scale screening indicate that in rich media, the class of Salmonella genes indispensable for growth is composed of approximately 490 genes...
  29. pmc Colonization of America by Drosophila subobscura: heterotic effect of chromosomal arrangements revealed by the persistence of lethal genes
    F Mestres
    , Facultat de Biologia, Universitat de Barcelona, Diagonal 645, 08071 Barcelona, Spain
    Proc Natl Acad Sci U S A 98:9167-70. 2001
    ..In Palearctic populations lethal genes are not associated in general with particular chromosomal arrangements...
  30. ncbi The art and design of genetic screens: caenorhabditis elegans
    Erik M Jorgensen
    Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA
    Nat Rev Genet 3:356-69. 2002
    ..Since 1974, when Sydney Brenner published his pioneering genetic screen, researchers have developed increasingly powerful methods for identifying genes and genetic pathways in C. elegans...
  31. pmc Perturbations in the spi1p GTPase cycle of Schizosaccharomyces pombe through its GTPase-activating protein and guanine nucleotide exchange factor components result in similar phenotypic consequences
    A Matynia
    Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Cell Biol 16:6352-62. 1996
  32. ncbi Genetic interactions between tumor suppressors Brca1 and p53 in apoptosis, cell cycle and tumorigenesis
    X Xu
    Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, 10 9N105, Bethesda, Maryland, USA
    Nat Genet 28:266-71. 2001
    ..These findings provide a mechanism for BRCA1-associated breast carcinogenesis...
  33. pmc The severe slow growth of Deltasrs2 Deltarqh1 in Schizosaccharomyces pombe is suppressed by loss of recombination and checkpoint genes
    Mohamed Maftahi
    Department of Environmental Health Sciences, Columbia University, Mailman School of Public Health and College of Physicians and Surgeons, Kolb Building, Room 114, 722 West 168th Street, New York, NY 10032, USA
    Nucleic Acids Res 30:4781-92. 2002
    ..This lethality is suppressed in a Deltarhp51 background. Together, these results demonstrate a clear genetic interaction between rqh1+, srs2+ and the genes of the homologous recombination pathway...
  34. pmc Genetic analyses of Schizosaccharomyces pombe dna2(+) reveal that dna2 plays an essential role in Okazaki fragment metabolism
    H Y Kang
    National Creative Research Initiative Center for Cell Cycle Control, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Changan Ku Suwon, Kyunggi Do, 440 746, Korea
    Genetics 155:1055-67. 2000
    ..We propose that dna2(+) acts as a central protein to form a complex with other proteins required to coordinate the multienzyme process for Okazaki fragment elongation and maturation...
  35. pmc Inactivation of CtIP leads to early embryonic lethality mediated by G1 restraint and to tumorigenesis by haploid insufficiency
    Phang Lang Chen
    Department of Biological Chemistry, College of Medicine, University of California Irvine, Sprague Hall, Room 124, Irvine, CA 92697, USA
    Mol Cell Biol 25:3535-42. 2005
    ..Taken together, this finding uncovers a novel G(1)/S regulation in that CtIP counteracts Rb-mediated G(1) restraint. Deregulation of this function leads to a defect in early embryogenesis and contributes, in part, to tumor formation...
  36. ncbi PS2 integrin requirements in Drosophila embryo and wing morphogenesis
    M C Brabant
    Department of Biochemistry, University of Arizona, Tucson 85721
    Dev Biol 157:49-59. 1993
    ..By varying times of transgene induction, we find that integrin function is required from very early in metamorphosis until at least the last 24-48 hr of wing development...
  37. ncbi Gene mapping within the T/t complex of the mouse. III: t-Lethal genes are arranged in three clusters on chromosome 17
    K Artzt
    Cell 39:565-72. 1984
    ..The overall picture emerges as three clusters of t-lethal genes: one near the proximally located tail interaction factor (tT) containing tw73; one numerous cluster associated ..
  38. ncbi Mutations in a novel gene, myoblast city, provide evidence in support of the founder cell hypothesis for Drosophila muscle development
    E Rushton
    Department of Zoology, University of Cambridge, UK
    Development 121:1979-88. 1995
    ..We suggest that this subset of myoblasts represents the proposed muscle founder cells and we draw an analogy between these founder cells and the muscle pioneers described for grasshopper muscle development...
  39. pmc Harlequin ichthyosis (ichq): a juvenile lethal mouse mutation with ichthyosiform dermatitis
    J P Sundberg
    Jackson Laboratory, Bar Harbor, Maine 04609 1500, USA
    Am J Pathol 151:293-310. 1997
    ..The harlequin ichthyosis mouse mutation is very similar to human type 2 harlequin ichthyosis for which it may be a good model...
  40. pmc Genes critical for muscle development and function in Caenorhabditis elegans identified through lethal mutations
    B D Williams
    Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110
    J Cell Biol 124:475-90. 1994
    ..Similar evidence suggests that one of the genes associated with mild effects on lattice assembly may code for tropomyosin. Many of the newly identified genes are likely to play critical roles in muscle development and function...
  41. pmc YB-1 is important for late-stage embryonic development, optimal cellular stress responses, and the prevention of premature senescence
    Zhi Hong Lu
    Division of Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Mol Cell Biol 25:4625-37. 2005
    ..These data suggest that YB-1 normally represses the transcription of CDK inhibitors, making it an important component of the cellular stress response signaling pathway...
  42. ncbi Small eyes (Sey): a homozygous lethal mutation on chromosome 2 which affects the differentiation of both lens and nasal placodes in the mouse
    B L Hogan
    J Embryol Exp Morphol 97:95-110. 1986
    ..Sey/Sey embryos develop to term but without eyes or nose, and die soon after birth. Further analysis of Sey/Sey embryos may throw light on the mechanisms underlying morphogenesis of craniofacial structures in mammals...
  43. ncbi Dominant lethality and insect population control
    Luke Alphey
    Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK
    Mol Biochem Parasitol 121:173-8. 2002
    ..We consider alternative strategies based on the use of conditional dominant lethals that are not always active in the environment...
  44. ncbi Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis
    Y Mishina
    Department of Molecular Genetics, University of Texas, M D Anderson Cancer Center, Houston 77030, USA
    Genes Dev 9:3027-37. 1995
  45. pmc Stage-specific apoptosis, developmental delay, and embryonic lethality in mice homozygous for a targeted disruption in the murine Bloom's syndrome gene
    N Chester
    Howard Hughes Medical Institute, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115 USA
    Genes Dev 12:3382-93. 1998
    ..Both the apoptotic wave and the appearance of micronuclei in red blood cells are likely cellular consequences of damaged DNA caused by effects on replicating or segregating chromosomes...
  46. ncbi Targeted disruption of the gene encoding DNA ligase IV leads to lethality in embryonic mice
    D E Barnes
    Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Curr Biol 8:1395-8. 1998
    ..Thus, unlike Ku70/80 and DNA-PKcs [11] [12] [13] [14], DNA ligase IV has an essential function in early mammalian development...
  47. ncbi Insect population control using a dominant, repressible, lethal genetic system
    D D Thomas
    Department of Zoology, Wellcome Trust Centre for the Epidemiology of Infectious Disease, Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK
    Science 287:2474-6. 2000
    ..Both methods work efficiently in Drosophila melanogaster, and we expect these principles to be widely applicable to more economically important organisms...
  48. pmc The conditional inactivation of the beta-catenin gene in endothelial cells causes a defective vascular pattern and increased vascular fragility
    Anna Cattelino
    FIRC Institute of Molecular Oncology, 16 20139, Milan, Italy
    J Cell Biol 162:1111-22. 2003
    ..This may become more marked when the vessels are exposed to high or turbulent flow, such as at bifurcations or in the beating heart, leading to fluid leakage or hemorrhages...
  49. pmc E-cadherin null mutant embryos fail to form a trophectoderm epithelium
    L Larue
    Max Planck Institut fur Immunbiologie, Freiburg, Germany
    Proc Natl Acad Sci U S A 91:8263-7. 1994
    ..These results demonstrate the pivotal role of E-cadherin in one of the most basic morphogenetic events in the development of multicellular organisms, the biogenesis of an epithelium...
  50. ncbi Searching for pattern and mutation in the Drosophila genome with a P-lacZ vector
    E Bier
    Howard Hughes Medical Institute, San Francisco, California
    Genes Dev 3:1273-87. 1989
    ..This type of screen appears to be an effective way to find new loci that may play a role in the development of the Drosophila nervous system...
  51. pmc A genetic method for generating Drosophila eyes composed exclusively of mitotic clones of a single genotype
    R S Stowers
    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA
    Genetics 152:1631-9. 1999
    ..We illustrate the utility of the method by applying it to lethal mutations in the synaptic transmission genes synaptotagmin and syntaxin...
  52. ncbi The glp-1 locus and cellular interactions in early C. elegans embryos
    J R Priess
    Medical Research Council, Laboratory of Molecular Biology, Cambridge, England
    Cell 51:601-11. 1987
    ..These mutations are all alleles of glp-1, a gene also involved in the control of germ cell proliferation during postembryonic development of C. elegans...
  53. ncbi Eco-friendly insect management
    Ernst A Wimmer
    Göttinger Zentrum für Molekulare Biowissenschaften GZMB, Institut fur Zoologie, Anthropologie und Entwicklungsbiologie, Georg August Universitat Gottingen, Justus von Liebig Weg 11, 37077 Gottingen, Germany
    Nat Biotechnol 23:432-3. 2005
  54. pmc Targeted disruption of the MKK4 gene causes embryonic death, inhibition of c-Jun NH2-terminal kinase activation, and defects in AP-1 transcriptional activity
    D Yang
    Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester 01605, USA
    Proc Natl Acad Sci U S A 94:3004-9. 1997
    ..These data establish that MKK4 is a JNK activator in vivo and demonstrate that MKK4 is an essential component of the JNK signal transduction pathway...
  55. pmc Expanded metabolic reconstruction of Helicobacter pylori (iIT341 GSM/GPR): an in silico genome-scale characterization of single- and double-deletion mutants
    Ines Thiele
    Department of Bioengineering, University of California San Diego, 9500 Gilman Dr 0412, La Jolla, CA 92093 0412, USA
    J Bacteriol 187:5818-30. 2005
    ..In addition, in silico double-deletion studies identified a total of 47 synthetic lethal mutants involving 67 different metabolic genes in rich medium...
  56. ncbi Constitutive NF-kappa B activation, enhanced granulopoiesis, and neonatal lethality in I kappa B alpha-deficient mice
    A A Beg
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Genes Dev 9:2736-46. 1995
    ..However, I kappa B alpha is required for the postinduction repression of NF-kappa B in fibroblasts. These results define distinct roles for the two forms of I kappa B and demonstrate the necessity for stringent control of NF-kappa B...
  57. pmc Mining protein networks for synthetic genetic interactions
    Sri R Paladugu
    Keck Graduate Institute of Applied Life Sciences, 535 Watson Drive, Claremont, CA 91711, USA
    BMC Bioinformatics 9:426. 2008
  58. ncbi Regulation of sexual differentiation in D. melanogaster via alternative splicing of RNA from the transformer gene
    R T Boggs
    Cell 50:739-47. 1987
    ..Substitution of a heat shock promoter for the tra promoter still leads to female-specific differentiation of otherwise tra-females. We suggest a mechanism by which Sex-lethal controls itself and tra...
  59. ncbi Involvement of the TRAP220 component of the TRAP/SMCC coactivator complex in embryonic development and thyroid hormone action
    M Ito
    Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, New York 10021, USA
    Mol Cell 5:683-93. 2000
    ..These results indicate that TRAP220 is essential for a wide range of physiological processes but also that it has gene- and activator-selective functions...
  60. ncbi Tumorigenesis and a DNA repair defect in mice with a truncating Brca2 mutation
    F Connor
    CRC Centre for Cell and Molecular Biology, Chester Beatty Laboratories, Institute of Cancer Research, London, UK
    Nat Genet 17:423-30. 1997
    ..We show that Brca2 is required for efficient DNA repair, and our results suggest that loss of the p53 checkpoint may be essential for tumour progression triggered by mutations in BRCA2...
  61. ncbi Evolutionary plasticity of genetic interaction networks
    Julia Tischler
    The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK
    Nat Genet 40:390-1. 2008
    ..Genetic interactions are therefore unlikely to represent simple redundancy between genes or pathways, and genetic interactions from yeast do not directly predict genetic interactions in higher eukaryotes, including humans...
  62. ncbi Synaptic transmission persists in synaptotagmin mutants of Drosophila
    A DiAntonio
    Department of Molecular and Cellular Physiology, Stanford University Medical Center, California 94305 5426
    Cell 73:1281-90. 1993
    ..The lethality of synaptotagmin in late first instar larvae is probably due to a perturbation of transmission that leaves the main apparatus for vesicle docking and fusion intact...
  63. ncbi Nup145p is required for nuclear export of mRNA and binds homopolymeric RNA in vitro via a novel conserved motif
    E Fabre
    European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany
    Cell 78:275-89. 1994
    ..Fragments of Nup145p and Nup116p including this motif bind specifically to homopolymeric RNAs in vitro. Nup145p, Nup116p, and Nup100p thus represent a novel class of nucleoporins involved in nucleocytoplasmic transport...
  64. ncbi Implications of high RNA virus mutation rates: lethal mutagenesis and the antiviral drug ribavirin
    Shane Crotty
    Department of Microbiology and Immunology, University of California, San Francisco 94143, USA
    Microbes Infect 4:1301-7. 2002
    ..In this review we discuss the genetic explanations, evolutionary implications, and drug development opportunities associated with RNA virus mutagenesis...
  65. ncbi Mutations affecting the cytoskeletal organization of syncytial Drosophila embryos
    W Sullivan
    Department of Biology, Sinsheimer Laboratories, University of California, Santa Cruz 95064
    Development 118:1245-54. 1993
    ..In addition to identifying new genes involved in cytoskeletal organization, these mutations provide insights into cytoskeletal function during early Drosophila embryogenesis...
  66. ncbi A dominant lethal genetic system for autocidal control of the Mediterranean fruitfly
    Peng Gong
    Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK
    Nat Biotechnol 23:453-6. 2005
    ..We show that these properties should prove advantageous for the implementation of insect pest control programs...
  67. ncbi Generation of a conditional Ppap2b/Lpp3 null allele
    Diana Escalante-Alcalde
    Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, USA
    Genesis 45:465-9. 2007
    ..A generalized Cre-mediated recombination of this allele yielded a phenotype fundamentally identical to our previously reported Ppap2b null allele...
  68. pmc Error-threshold exists in fitness landscapes with lethal mutants
    Nobuto Takeuchi
    BMC Evol Biol 7:15; author reply 15. 2007
    ..In this article, we study whether the above conclusion holds in high-dimensional genotype space without the assumption of the adjacency of mutations, where the consequences of mutation-selection dynamics can be qualitatively different...
  69. pmc Modeling synthetic lethality
    Nolwenn Le Meur
    Division of Public Health Sciences, Fred Hutchinson Cancer Center Research, Program in Computational Biology, Seattle, WA 98109, USA
    Genome Biol 9:R135. 2008
    ..We propose statistical and computational tools that can be used to find relationships between synthetic lethality and cellular organizational units...
  70. pmc Suppressors of spindle checkpoint defect (such) mutants identify new mdf-1/MAD1 interactors in Caenorhabditis elegans
    Maja Tarailo
    Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    Genetics 175:1665-79. 2007
    ..elegans. The such-1/APC5-like mutation, h1960, significantly delays anaphase onset both in germline and in early embryonic cells...
  71. pmc Growth retardation, DNA repair defects, and lack of spermatogenesis in BRCA1-deficient mice
    V L Cressman
    Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Mol Cell Biol 19:7061-75. 1999
  72. ncbi Genetic and electrophysiological studies of Drosophila syntaxin-1A demonstrate its role in nonneuronal secretion and neurotransmission
    K L Schulze
    Howard Hughes Medical Institute, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030
    Cell 80:311-20. 1995
    ..These data demonstrate that syntaxin plays a key role in nonneuronal secretion and is absolutely required for evoked neurotransmission...
  73. ncbi Integrated genomic and pharmacological approaches to identify synthetic lethal genes as cancer therapeutic targets
    Shinji Mizuarai
    Department of Cancer Research, Banyu Tsukuba Research Institute, Merck Research Laboratory, Tsukuba, Ibaraki 300 2611, Japan
    Curr Mol Med 8:774-83. 2008
    ..This review introduces the research that could successfully identify synthetic lethal genes in cancer cells harboring major gene alterations such as p53, RB, K-Ras, or Myc...
  74. pmc Drosophila beta spectrin functions independently of alpha spectrin to polarize the Na,K ATPase in epithelial cells
    R R Dubreuil
    Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, IL 60637, USA
    J Cell Biol 149:647-56. 2000
    ..The results establish a role for beta spectrin in determining the subcellular distribution of the Na, K ATPase and, unexpectedly, this role is independent of alpha spectrin...
  75. ncbi Involvement of yeast carboxy-terminal domain kinase I (CTDK-I) in transcription elongation in vivo
    G Jona
    Department of Molecular Genetics, The Weizmann Institute of Science, 76100, Rehovot, Israel
    Gene 267:31-6. 2001
    ..Our results suggest that CTDK-I plays an important role in transcriptional elongation in vivo, possibly by creating a form of RNA polymerase that is less prone to transcriptional arrest...
  76. pmc Neuronal abnormalities in microtubule-associated protein 1B mutant mice
    W Edelmann
    Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 93:1270-5. 1996
    ..Similar histological and immunochemical changes were observed in the olfactory bulb, hippocampus, and retina, providing a basis for the observed phenotypes...
  77. ncbi Inactivation of the glycine transporter 1 gene discloses vital role of glial glycine uptake in glycinergic inhibition
    Jesus Gomeza
    Department of Neurochemistry, Max Planck Institute for Brain Research, Deutschordenstrasse 46, 60528 Frankfurt, Germany
    Neuron 40:785-96. 2003
    ..Thus, during early postnatal life, GlyT1 is essential for regulating glycine concentrations at inhibitory GlyRs, and GlyT1 deletion generates symptoms found in human glycine encephalopathy...
  78. ncbi Components of the spindle-assembly checkpoint are essential in Caenorhabditis elegans
    R Kitagawa
    Department of Medical Genetics, University of British Columbia, 6174 University Boulevard, Vancouver, British Columbia V6T 1Z3, Canada
    Nat Cell Biol 1:514-21. 1999
    ..In the absence of mdf gene products, errors in chromosome segregation arise and accumulate, ultimately leading to genetic lethality...
  79. pmc BIM1 encodes a microtubule-binding protein in yeast
    K Schwartz
    Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA
    Mol Biol Cell 8:2677-91. 1997
    ..One of the human homologues, EB1, has been reported previously as binding APC, itself a microtubule-binding protein and the product of a gene implicated in the etiology of human colon cancer...
  80. ncbi Mekk3 is essential for early embryonic cardiovascular development
    J Yang
    Department of Immunology, The University of Texas M D Anderson Cancer Center, Houston, Texas, USA
    Nat Genet 24:309-13. 2000
    ..We conclude that Mekk3 is necessary for blood vessel development and may be a possible target for drugs that control angiogenesis...
  81. ncbi Silencing the Drosophila ribosomal protein L14 gene using targeted RNA interference causes distinct somatic anomalies
    Espen Enerly
    Division of Cell and Molecular Biology, Institute of Biology, University of Oslo, Blindernveien 31, N 0315 Oslo, Norway
    Gene 320:41-8. 2003
    ..We show, at the RNA and phenotypic levels, that RNAi efficiently reduces RpL14 gene expression throughout development, causing lethality and distinct and dramatic somatic anomalies in both developing and differentiated cells...
  82. pmc The Arabidopsis PILZ group genes encode tubulin-folding cofactor orthologs required for cell division but not cell growth
    Katharina Steinborn
    ZMBP, Entwicklungsgenetik, Universitat Tubingen, D 72076 Tubingen, Germany
    Genes Dev 16:959-71. 2002
  83. pmc Synthetic lethality of Drosophila in the absence of the MUS81 endonuclease and the DmBlm helicase is associated with elevated apoptosis
    Kirsten Trowbridge
    Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA
    Genetics 176:1993-2001. 2007
    ..Lethality and elevated apoptosis were partially suppressed by a mutation in spn-A, which encodes the ortholog of the strand invasion protein Rad51. These findings provide insights into the causes of synthetic lethality...
  84. ncbi DNA helicase gene interaction network defined using synthetic lethality analyzed by microarray
    Siew Loon Ooi
    Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, 617 Hunterian Building, 725 North Wolfe Street, Baltimore, Maryland 21205, USA
    Nat Genet 35:277-86. 2003
    ..SLAM detects synthetic lethality efficiently and ranks candidate genetic interactions, making it an especially useful method...
  85. ncbi Mob2p interacts with the protein kinase Orb6p to promote coordination of cell polarity with cell cycle progression
    Ming Chin Hou
    Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Cell Sci 116:125-35. 2003
    ..Our results suggest that Mob2p, along with Orb6p, is required for coordinating polarized cell growth during interphase with the onset of mitosis...
  86. ncbi Targeted disruption of the neurochondrin/norbin gene results in embryonic lethality
    Reiko Mochizuki
    Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki 305 8577, Japan
    Biochem Biophys Res Commun 310:1219-26. 2003
    ..5 and 6.5 dpc. This result indicates that neurochondrin/norbin gene function is essential for the early embryogenesis...
  87. ncbi A transgene-based, embryo-specific lethality system for insect pest management
    Carsten Horn
    Lehrstuhl fur Genetik, Universitat Bayreuth, Universitätsstrasse 30 NWI, 95447 Bayreuth, Germany
    Nat Biotechnol 21:64-70. 2003
    ..The embryonic lethality can be suppressed maternally, which will allow it to be combined with transgenic female-specific lethality systems to raise only vigorous but sterile males...
  88. ncbi Reverse genetics of essential genes in tissue-culture cells: 'dead cells talking'
    Damien F Hudson
    Wellcome Trust Centre for Cell Biology, ICMB, Swann Building, University of Edinburgh, UK
    Trends Cell Biol 12:281-7. 2002
    ..These include gene targeting in mouse, human and chicken DT40 cells, and recent advances in double-stranded RNA-mediated interference (RNAi)...
  89. pmc Lamin B1 is required for mouse development and nuclear integrity
    Laurent Vergnes
    Veterans Affairs Greater Los Angeles Healthcare System, David Geffen School of Medicine, University of California, Los Angeles, CA 90073, USA
    Proc Natl Acad Sci U S A 101:10428-33. 2004
    ..These mutant mice and cell lines derived from them will be useful models for studying the role of the nuclear lamina in various cellular processes...
  90. pmc Embryonic lethality and fetal liver apoptosis in mice lacking the c-raf-1 gene
    M Mikula
    Department of Cell and Microbiology, Institute of Microbiology and Genetics and Research Institute of Molecular Pathology, Vienna Biocenter, 1030 Vienna, Austria
    EMBO J 20:1952-62. 2001
    ..These results indicate that the essential function of Raf-1 is to counteract apoptosis rather than to promote proliferation, and that effectors distinct from the MEK/ERK cascade must mediate the anti-apoptotic function of Raf-1...
  91. ncbi The GAGA factor is required in the early Drosophila embryo not only for transcriptional regulation but also for nuclear division
    K M Bhat
    Department of Molecular Biology, Princeton University, NJ 08544, USA
    Development 122:1113-24. 1996
    ..These defects are likely to be related to the association of the GAGA protein with heterochromatic satellite sequences which is observed throughout the cell cycle...
  92. pmc Destabilization of yeast micro- and minisatellite DNA sequences by mutations affecting a nuclease involved in Okazaki fragment processing (rad27) and DNA polymerase delta (pol3-t)
    R J Kokoska
    Department of Biology and Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill 27599, USA
    Mol Cell Biol 18:2779-88. 1998
    ..We also found that rad27 and pol3-01 (an allele carrying a mutation in the "proofreading" exonuclease domain of DNA polymerase delta) mutations were synthetically lethal...
  93. pmc On biological functions mapping to the heterochromatin of Drosophila melanogaster
    S Pimpinelli
    Genetics 109:701-24. 1985
    ..Some general implications of these inferences are considered...
  94. pmc Bypassing anaphase by fission yeast cut9 mutation: requirement of cut9+ to initiate anaphase
    I Samejima
    Department of Biophysics, Faculty of Science, Kyoto University, Japan
    J Cell Biol 127:1655-70. 1994
    ..The nuc2+ and cut9+ genes share an essential function to initiate anaphase. The cold-sensitive scn1 and scn2 mutations, defective in late anaphase, can suppress the ts phenotype of cut9...
  95. ncbi Mutational analysis of Saccharomyces cerevisiae ARF1
    R A Kahn
    Laboratory of Biological Chemistry, NCI, National Institutes of Health, Bethesda, Maryland 20892
    J Biol Chem 270:143-50. 1995
    ..Two high-copy suppressors of this conditional phenotype were cloned and sequenced. One of these suppressors, SFS4, was found to be identical to PBS2/HOG4, recently shown to encode a microtubule-associated protein kinase kinase in yeast...
  96. pmc Neural tube defects and abnormal brain development in F52-deficient mice
    M Wu
    Howard Hughes Medical Institute, Center for Learning and Memory, Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 93:2110-5. 1996
    ..Disruption of F52 in mice therefore identifies a gene whose mutation results in isolated neural tube defects and may provide an animal model for common human neural tube defects...
  97. ncbi Hybrid lethal systems in the Drosophila melanogaster species complex
    K Sawamura
    Department of Biology, School of Education, Waseda University, Tokyo, Japan
    Genetica 88:175-85. 1993
  98. pmc Unexpected combinations of null mutations in genes encoding the actin cytoskeleton are lethal in yeast
    A E Adams
    Department of Molecular and Cellular Biology, Life Sciences South, University of Arizona, Tuscon 85721
    Mol Biol Cell 4:459-68. 1993
    ..Determination of the molecular basis for this surprising conclusion will provide unique insights into the essential mechanisms that regulate the actin cytoskeleton...
  99. pmc Establishing genetic interactions by a synthetic dosage lethality phenotype
    E S Kroll
    Department of Molecular Biology and Genetics, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA
    Genetics 143:95-102. 1996
    ..Furthermore, synthetic dosage lethality is easily adapted to the study of cloned genes in other organisms...
  100. ncbi Mutations in the carboxyl-terminal propeptide of the pro alpha 1(I) chain of type I collagen result in defective chain association and produce lethal osteogenesis imperfecta
    S D Chessler
    Department of Pathology, University of Washington, Seattle 98195
    J Biol Chem 268:18218-25. 1993
    ..These findings extend the range of lethal mutations in the type I collagen genes and help to identify regions of the carboxyl-terminal propeptide that may be important for chain-chain recognition and molecular assembly...
  101. pmc Actin organization, bristle morphology, and viability are affected by actin capping protein mutations in Drosophila
    R Hopmann
    Department of Biology, Washington University, St Louis, Missouri 63130, USA
    J Cell Biol 133:1293-305. 1996
    ..Our data demonstrate that CP has an essential function during development, and further suggest that CP is required to regulate actin assembly during the development of specialized structures that depend on actin for their morphology...

Research Grants62

    John Schimenti; Fiscal Year: 2009
    ..Many of the uncloned mutations currently map to regions containing none or few known lethal genes, ensuring that several new essential genes or functional elements will be identified...
  2. Genetics and Biology of Pancreatic Ductal Adenocarcinoma
    RONALD ANTHONY DEPINHO; Fiscal Year: 2013
    ..MIT) with the integrating goals of determining the roles of KRAS* synthetic lethal genes in PDAC development and maintenance, the effect of co-extinction of PI3K/MEK pathways In PDAC and associated ..
  3. Exploiting synthetic lethality of hematopoietic lineage cells to develop novel ta
    KYLE RUSSELL BONNEAU; Fiscal Year: 2012
    ..Identification of these hematopoieitc-specific lethal genes would allow for the development of novel targeted therapies for combating diverse blood cancers, and for ..
  4. Evolution of cancer-specific molecular requirements for glioblastoma multiforme (
    Jun Zhu; Fiscal Year: 2013
    ..for Glioblastoma multiforme (GBM), an incurable form of brain cancer, we have demonstrated the existence of GBM-lethal genes, which when inhibited render patient GBM tumor cells sensitive to cellular stresses that arise as a consequence ..
  5. Genetic elements of cancer cell survival in tumor microenvironment stresses
    MELISSA M KEENAN; Fiscal Year: 2013
    ..Our lab recently identified synthetically lethal genes for breast cancer cell survival under one TME stress, and so we expect that applying the concept genome-wide is ..
    Bruce Baker; Fiscal Year: 1999
    ..The genetic analysis of dosage compensation in Drosophila has lead to the discovery of four male specific lethal genes and which appear to be the primary mediators of dosage compensation while the sex-lethal gene, also a ..
  7. The Ubiquitin-Proteasome System in Metazoan Embryogenesis
    Zhirong Bao; Fiscal Year: 2013
    ..We have identified ~50 conserved, embryonic lethal genes that are required for UPS substrate specificity...
  8. Model-guided Identification of Synthetic Lethal Genes for Drug Target Development
    Bernhard O Palsson; Fiscal Year: 2013
  9. RNA Interference in Drosophila
    Dean Smith; Fiscal Year: 2007
    ..clones will be restricted to the compound eye, therefore we will recover mutations in viable and in potentially lethal genes required for RNAi not identified in other systems, 3...
    Nancy Hopkins; Fiscal Year: 2003
    ..The embryonic lethal genes of zebrafish are require for the normal patterning, growth and differentiation of the fish embryo, including ..
  11. Completion of a Large Insertional Screen in Zebrafish
    Nancy Hopkins; Fiscal Year: 2005
    ..The majority of such embryonic mutants are lethal. To rapidly clone the embryonic lethal genes of the zebrafish, our lab developed and applied a method of insertional mutagenesis...
  12. Localization of Recombination sites in E. coli
    Steven J Sandler; Fiscal Year: 2010
    ..These new reagents will also provide important molecular tools for others in the research community. PHS 398 (Rev. 09/04) Page 2 Principal Investigator/Program Director (Last, first, middle): SANDLER, STEVEN, J ..
  13. Population genetics of transgenes in mosquito vectors
    Fred Gould; Fiscal Year: 2008
    ..A user-friendly form of the models as well as an accessible manual will be developed and placed on the internet. ..
  14. Mouse Mutagenesis Workshops
    David Beier; Fiscal Year: 2006
    ..Ultimately, this workshop will serve the goal of improving public health by facilitating the generation and utilization of model systems for biomedical investigation. ..
  15. Small Laboratory Animal Imaging: High Resolution Microcomputed Tomography System
    RAMIRO TORIBIO; Fiscal Year: 2006
    ..Salary and benefits for the Supervisor and Space and utilities for the instrument will be provided by Department of Veterinary Biosciences and the College of Veterinary Medicine. [unreadable] [unreadable]..
  16. ROS induced cellular toxicity and tissue damage
    Atanu Duttaroy; Fiscal Year: 2006
    ..Depletion of MnSOD function from each of these tissues will provide important insight regarding the contribution of ROS towards cellular aging. [unreadable] [unreadable]..
  17. Involvement of a K+ Channel in C. elegans Male Behavior
    ELIZABETH DESTASIO; Fiscal Year: 2005
    ..Lastly, this research will help delineate the connections between motility, functions of particular muscle cells, and organismal behavior. ..
  18. Function and evolution of microRNAs
    Fabio Piano; Fiscal Year: 2006
    ..This project is an intensive collaboration between a bioinformatics lab (focused on gene regulatory processes), and an experimental lab (RNAi functional genomics in nematodes) [unreadable] [unreadable]..
  19. Genome Instability in Cells and Tissues of the Zebrafish
    Forrest Spencer; Fiscal Year: 2006
    ..abstract_text> ..
  20. 2006 Cancer Model Mechanisms
    William Kaelin; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  21. Epigenetic Regulation of Gene Expression During Early Mouse Embryogenesis
    M Smith; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
    DAVID O BROCHTA; Fiscal Year: 2008
    ..gambiae populations, 3) develop Herves into a mosquito gene vector. These aims will be accomplished by performing a combination of laboratory and field-based studies using molecular and population genetics tools. ..
  23. Dopamine Receptor Regulation by GRKs in Drug Abuse
    Richard Premont; Fiscal Year: 2008
    ..The results of these studies will define the role of GRK6 in setting the basal tone of dopamine signaling in the striatum. [unreadable] [unreadable] [unreadable]..
    Carl Frieden; Fiscal Year: 2008
    ..Both these projects employ novel real-time and equilibrium NMR methodology in addition to standard. ..
  25. Genetic Analysis of Developmental Mutations
    David Beier; Fiscal Year: 2007
    ..Finally, for a small number of mice, we will attempt to identify the causal locus by positional cloning, with an aim towards developing the most efficient protocols for this. ..
  26. CNS Stem Cells for Alzheimer's Disease Therapy
    George Carlson; Fiscal Year: 2005
    ..The objectives of this grant are to test human neural stern cells as candidate therapeutics for the treatment of Alzheimer's disease. ..
    Phyllis Faust; Fiscal Year: 2002
    Atanu Duttaroy; Fiscal Year: 2002
    Marnie Halpern; Fiscal Year: 2001
    ..As in non-vertebrate genetic systems, a zebrafish deletion panel is an essential resource, providing the necessary bridge between DNA sequence and gene function. ..
  30. Evolutionary genomics of new Drosophila genes
    DAVEN PRESGRAVES; Fiscal Year: 2004
    ..The methods developed will be applicable in comparative analysis of other genomes, including those of humans and their primate relatives. ..
    Thao Dang; Fiscal Year: 2005
    ..The support given by this K08 award will allow Dr. Dang to build on her existing knowledge and promote her transition to an independent investigator in a highly competitive environment. ..
  32. Function and Mechanisms of the N-End Rule Pathway
    Yong Tae Kwon; Fiscal Year: 2007
    ..abstract_text> ..
    Michel Sadelain; Fiscal Year: 2004
  34. Myosins VIIA, VIIB & XV in Fly Hearing and Morphogenesis
    DANIEL KIEHART; Fiscal Year: 2009
    ..Together, our studies offer unique opportunities to probe the supramolecular protein complexes that require motor protein function and that drive cellular function in auditory reception, vestibular function and morphogenesis. ..
  35. Proteomics of Ubiquitin-Dependent N-End Rule Pathway
    Yong Tae Kwon; Fiscal Year: 2009
    ..We will examine the physiological significance underlying the N-end rule dependent proteolysis of RGS4, -5, and -16, emerging in vivo N-end rule substrates. ..
    Domenico Accili; Fiscal Year: 2009
    ..abstract_text> ..
  37. The Role of MYST histone acetyltransferases in genome stability
    M Smith; Fiscal Year: 2008
    ..These experiments will greatly expand our understanding of Hbo1 function in regulating DNA replication and cell proliferation. ..
    Matteo Pellegrini; Fiscal Year: 2002
    ..Those with roles related to virulence will serve as new, previously unknown targets for therapeutic drugs. Once experimentally validated, these targets will be marketed to our pharmeceutical customers and partners. ..
  39. Gap Junction Mediated Signaling and Vascular Responses
    Alexander M Simon; Fiscal Year: 2010
    ..Finally, these studies could also lead to new approaches to control vasculogenesis and angiogenesis in other clinically important settings, such as anti-angiogenesis treatments designed to fight cancer. ..
  40. Mutagenesis of the Mammalian Imprinting Process(es)
    Eugene Rinchik; Fiscal Year: 2002
    ..abstract_text> ..
  41. Mammalian Mitochondrial One-Carbon Metabolism
    DEAN RAMSAY APPLING; Fiscal Year: 2010
    ..abstract_text> ..
    Robert Kass; Fiscal Year: 2001
    Tomohiro Matsumoto; Fiscal Year: 2001
    John Roth; Fiscal Year: 2004
    ..coli. Understanding this metabolism may contribute to understanding the natural lifestyle of Salmonellae. ..
  45. Targeting of 6-Phosphofructo-2 kinase in Cancer
    Jason Chesney; Fiscal Year: 2008
    ..We expect that these studies will support the role of iPFK-2 as the molecular target of F6P33 and thus validate the development of small molecule inhibitors of iPFK-2 as antineoplastic agents. [unreadable] [unreadable]..
    DEAN APPLING; Fiscal Year: 2005
    ..abstract_text> ..
  47. Using Synthetic Lethality to Select Cancer Drug Targets
    William Kaelin; Fiscal Year: 2005
    ..Moreover, they may establish a new paradigm for the selection of anticancer drug targets based on inactivating mutations of TSG. ..
  48. Dynamic Regulation of y-Globin mRNA Stability
    J Russell; Fiscal Year: 2004
  49. Genetic Manipulation of Insects
    DAVID O BROCHTA; Fiscal Year: 2004
    ..The meeting is an uncommon opportunity for graduate students and postdoctoral fellows to obtain a high level synopsis of the field of insect molecular genetics and to make important career-advancing interactions. ..
  50. Chromosome Transmission Fidelity
    Forrest Spencer; Fiscal Year: 2004
    Erik Jorgensen; Fiscal Year: 2004
    ..Ultimately, these studies might help explain the molecular behavior of neuroactive drugs and lead to the development of new and more specific pharmaceuticals which act on individual neurotransmitter systems. ..
  52. CNS defects in a murine Zellweger syndrome model
    Phyllis Faust; Fiscal Year: 2007
  53. Elucidating the Function of Novel Epigenetic Element
    HEATHER TRUE KROB; Fiscal Year: 2005
  54. Emerging Mechanisms of Epigenetic Regulation
    JEANNIE LEE; Fiscal Year: 2003
    ..Appreciate the agricultural implications of epigenetics, such as those relating to plant viral defense mechanisms, animal cloning, and imprinting. ..
  55. 24-Capillary Reveal Mutation Discovery System
    George Carlson; Fiscal Year: 2003
    ..The Spectrumedix Reveal 2410 will not only accelerate current research at McLaughlin Research Institute, but help in recruiting new biomedical researchers in the field of neurogenetics. ..
  56. PTHrP on normal osteoblast differentiation and function
    RAMIRO TORIBIO; Fiscal Year: 2008
    ..Dr. Thomas Rosol's laboratory will provide an excellent environment for developing the skills necessary to become a successful independent researcher. ..
    DANIEL KIEHART; Fiscal Year: 2002
    ..5 to 1 billion years of evolution that separate insects from mammals. Together, they promise to bring the powerful tools of Drosophila genetics and molecular genetics to bear on this important biological problem. ..
  58. Tn5 as an insect genomics tool
    DAVID O BROCHTA; Fiscal Year: 2002
    ..gambiae make this is a high risk project but one whose impact on the field of medical entomology and efforts to control the transmission of malaria will be enormous if it is successful. ..
  59. A Luciferase Fusion Protein Library to Identify & Monitor Ubiquitylation Targets
    William Kaelin; Fiscal Year: 2008
    ..Reisolation of HIF in aims 2 and 3 would constitute proof of concept with respect to the potential utility of this approach. ..
  60. Real-Time Imaging of Hypoxia based on VHL Activity
    William Kaelin; Fiscal Year: 2006
    ..unreadable] [unreadable]..