D Horn

Summary

Affiliation: London School of Hygiene and Tropical Medicine
Country: UK

Publications

  1. pmc Deletion of a trypanosome telomere leads to loss of silencing and progressive loss of terminal DNA in the absence of cell cycle arrest
    Lucy Glover
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Nucleic Acids Res 35:872-80. 2007
  2. pmc Sequence homology and microhomology dominate chromosomal double-strand break repair in African trypanosomes
    Lucy Glover
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Nucleic Acids Res 36:2608-18. 2008
  3. pmc Two essential MYST-family proteins display distinct roles in histone H4K10 acetylation and telomeric silencing in trypanosomes
    Taemi Kawahara
    London School of Hygiene and Tropical Medicine, London, UK
    Mol Microbiol 69:1054-68. 2008
  4. pmc Histone deacetylases play distinct roles in telomeric VSG expression site silencing in African trypanosomes
    Qiao Ping Wang
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Mol Microbiol 77:1237-45. 2010
  5. pmc High-throughput decoding of antitrypanosomal drug efficacy and resistance
    Sam Alsford
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Nature 482:232-6. 2012
  6. pmc Microhomology-mediated deletion and gene conversion in African trypanosomes
    Lucy Glover
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Nucleic Acids Res 39:1372-80. 2011
  7. pmc DNA break site at fragile subtelomeres determines probability and mechanism of antigenic variation in African trypanosomes
    Lucy Glover
    London School of Hygiene and Tropical Medicine, London, United Kingdom
    PLoS Pathog 9:e1003260. 2013
  8. pmc Cell-cycle-regulated control of VSG expression site silencing by histones and histone chaperones ASF1A and CAF-1b in Trypanosoma brucei
    Sam Alsford
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Nucleic Acids Res 40:10150-60. 2012
  9. pmc Trypanosomal histone γH2A and the DNA damage response
    Lucy Glover
    London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
    Mol Biochem Parasitol 183:78-83. 2012
  10. pmc RNA interference, growth and differentiation appear normal in African trypanosomes lacking Tudor staphylococcal nuclease
    Sam Alsford
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Mol Biochem Parasitol 174:70-3. 2010

Collaborators

Detail Information

Publications48

  1. pmc Deletion of a trypanosome telomere leads to loss of silencing and progressive loss of terminal DNA in the absence of cell cycle arrest
    Lucy Glover
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Nucleic Acids Res 35:872-80. 2007
    ..The results provide direct evidence for telomere-dependent repression but suggest a telomere-independent mode of VSG-silencing. They also indicate the absence of a telomere-loss checkpoint in T. brucei...
  2. pmc Sequence homology and microhomology dominate chromosomal double-strand break repair in African trypanosomes
    Lucy Glover
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Nucleic Acids Res 36:2608-18. 2008
    ..These DSBR pathways available to T. brucei likely underlie patterns of antigenic variation and the evolution of the vast VSG gene family...
  3. pmc Two essential MYST-family proteins display distinct roles in histone H4K10 acetylation and telomeric silencing in trypanosomes
    Taemi Kawahara
    London School of Hygiene and Tropical Medicine, London, UK
    Mol Microbiol 69:1054-68. 2008
    ..The results are also consistent with the idea that HAT1 contributes to establishing boundaries between transcriptionally active and repressed telomeric domains in T. brucei...
  4. pmc Histone deacetylases play distinct roles in telomeric VSG expression site silencing in African trypanosomes
    Qiao Ping Wang
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Mol Microbiol 77:1237-45. 2010
    ..We conclude that DAC1 and DAC3 play distinct roles in subtelomeric gene silencing and that DAC3 represents the first readily druggable target linked to VSG ES control in the African trypanosome...
  5. pmc High-throughput decoding of antitrypanosomal drug efficacy and resistance
    Sam Alsford
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Nature 482:232-6. 2012
    ....
  6. pmc Microhomology-mediated deletion and gene conversion in African trypanosomes
    Lucy Glover
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Nucleic Acids Res 39:1372-80. 2011
    ..We discuss the contribution of MMEJ pathways to genome evolution, subtelomere recombination and antigenic variation...
  7. pmc DNA break site at fragile subtelomeres determines probability and mechanism of antigenic variation in African trypanosomes
    Lucy Glover
    London School of Hygiene and Tropical Medicine, London, United Kingdom
    PLoS Pathog 9:e1003260. 2013
    ..Our results show how subtelomere fragility can generate the triggers for the major antigenic variation mechanisms in the African trypanosome...
  8. pmc Cell-cycle-regulated control of VSG expression site silencing by histones and histone chaperones ASF1A and CAF-1b in Trypanosoma brucei
    Sam Alsford
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Nucleic Acids Res 40:10150-60. 2012
    ..Defects in these functions typically lead to arrest in S-phase but defective cells can also progress through the cell cycle leading to nucleosome depletion and derepression of telomeric VSG ESs...
  9. pmc Trypanosomal histone γH2A and the DNA damage response
    Lucy Glover
    London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
    Mol Biochem Parasitol 183:78-83. 2012
    ..The results link trypanosomal γH2A, with an unusual histone modification motif, to DNA damage sensing and mitotic checkpoint signaling...
  10. pmc RNA interference, growth and differentiation appear normal in African trypanosomes lacking Tudor staphylococcal nuclease
    Sam Alsford
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Mol Biochem Parasitol 174:70-3. 2010
    ..We conclude that if this nuclease plays a role in the destruction or processing of dsRNA, mRNA or siRNA in the RNAi pathway, it is likely a minor one...
  11. pmc Genome-wide RNAi screens in African trypanosomes identify the nifurtimox activator NTR and the eflornithine transporter AAT6
    Nicola Baker
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Mol Biochem Parasitol 176:55-7. 2011
    ..Thus, bloodstream-form T. brucei RNAi libraries present a versatile tool for selective genetic screening and for the rapid identification of drug-activation, uptake and potential resistance mechanisms...
  12. pmc Site-specific DNA double-strand breaks greatly increase stable transformation efficiency in Trypanosoma brucei
    Lucy Glover
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Mol Biochem Parasitol 166:194-7. 2009
    ..In the example presented, more than 1% of cells that survive the procedure were transformed generating 80,000 transformants from a typical experiment...
  13. pmc DNA breaks as triggers for antigenic variation in African trypanosomes
    Sam Alsford
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E7HT, UK
    Genome Biol 10:223. 2009
    ..The DNA repair machinery has been co-opted for antigenic variation in African trypanosomes. New work directly demonstrates that a double-strand break initiates a switch in the expressed variant surface coat...
  14. pmc Molecular mechanisms underlying the control of antigenic variation in African trypanosomes
    David Horn
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Curr Opin Microbiol 13:700-5. 2010
    ..We describe the factors and sequences recently linked to mutually exclusive transcription and VSG recombination, and how these act in the control of the key virulence mechanism of antigenic variation...
  15. pmc Telomere maintenance and length regulation in Trypanosoma brucei
    D Horn
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    EMBO J 19:2332-9. 2000
    ..Telomere length regulation in T.brucei is discussed in the context of recent results from other cell types...
  16. pmc Codon usage suggests that translational selection has a major impact on protein expression in trypanosomatids
    David Horn
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    BMC Genomics 9:2. 2008
    ..Thus, trypanosomatids must use post-transcriptional control mechanisms to balance gene expression requirements...
  17. ncbi request reprint Nuclear gene transcription and chromatin in Trypanosoma brucei
    D Horn
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Int J Parasitol 31:1157-65. 2001
    ..Here, I discuss and compare nuclear gene transcription in T. brucei with transcription in other eucaryotes focusing in particular on mono-allelic transcription of genes that encode the variant surface glycoproteins...
  18. ncbi request reprint Histone deacetylases
    David Horn
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Adv Exp Med Biol 625:81-6. 2008
    ..These enzymes are now being characterised and assessed for chemotherapeutic potential...
  19. ncbi request reprint The central roles of telomeres and subtelomeres in antigenic variation in African trypanosomes
    David Horn
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Chromosome Res 13:525-33. 2005
    ..Current research addresses the role of telomeres in the conversion and silencing mechanisms and in the diversification of the VSG archive...
  20. ncbi request reprint Antigenic variation: extending the reach of telomeric silencing
    David Horn
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Curr Biol 19:R496-8. 2009
    ..Work on the RAP1 telomere-binding protein now indicates that silencing spreads over a sufficient distance to repress these genes...
  21. ncbi request reprint Directional enrichment of directly cloned PCR products
    David Horn
    London School of Hygiene and Tropical Medicine, London, UK
    Biotechniques 39:40, 42, 44, 46. 2005
  22. pmc Introducing histone modification in trypanosomes
    David Horn
    London School of Hygiene and Tropical Medicine, Keppel Street, London, UK
    Trends Parasitol 23:239-42. 2007
    ..Future studies should provide insights into the genomic distribution of each modification and their roles in growth and pathogenesis...
  23. ncbi request reprint The molecular control of antigenic variation in Trypanosoma brucei
    David Horn
    Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Curr Mol Med 4:563-76. 2004
    ....
  24. ncbi request reprint Histone deacetylases in Trypanosoma brucei: two are essential and another is required for normal cell cycle progression
    Alexandra K Ingram
    Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, UK
    Mol Microbiol 45:89-97. 2002
    ..Our results provide genetic validation of DAC1 and DAC3 as potential chemotherapy targets and demonstrate that T. brucei expresses at least three probable histone deacetylases with distinct function...
  25. ncbi request reprint Genetic manipulation indicates that ARD1 is an essential N(alpha)-acetyltransferase in Trypanosoma brucei
    A K Ingram
    London School of Hygiene and Tropical Medicine, UK
    Mol Biochem Parasitol 111:309-17. 2000
    ..cerevisiae, ARD1 is an essential gene in T. brucei. We propose that protein modification by ARD1 is essential for viability in mammalian and insect-stage T. brucei cells...
  26. pmc Repression of polymerase I-mediated gene expression at Trypanosoma brucei telomeres
    Lucy Glover
    London School of Hygiene and Tropical Medicine, London, UK
    EMBO Rep 7:93-9. 2006
    ..Our results show constitutive telomeric repression in T. brucei and indicate that an enhanced, developmental stage-specific repression mechanism controls antigenic variation...
  27. pmc Multiplex analysis of RNA interference defects in Trypanosoma brucei
    Sam Alsford
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Mol Biochem Parasitol 139:129-32. 2005
  28. pmc Vitamin C biosynthesis in trypanosomes: a role for the glycosome
    Shane R Wilkinson
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    Proc Natl Acad Sci U S A 102:11645-50. 2005
    ..It is implicit, therefore, that bloodstream-form trypanosomes also possess a capacity for ascorbate transport...
  29. ncbi request reprint RNA interference identifies two hydroperoxide metabolizing enzymes that are essential to the bloodstream form of the african trypanosome
    Shane R Wilkinson
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    J Biol Chem 278:31640-6. 2003
    ..These experiments therefore identify redox pathways that are essential for oxidative defense in T. brucei and validate the corresponding peroxidases as targets for drug design...
  30. ncbi request reprint Functional characterisation of the iron superoxide dismutase gene repertoire in Trypanosoma brucei
    Shane R Wilkinson
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
    Free Radic Biol Med 40:198-209. 2006
    ..These experiments therefore identify essential components of the superoxide metabolising arm of the T. brucei oxidative defence system and validate these enzymes as parasite-specific targets for drug design...
  31. ncbi request reprint A sirtuin in the African trypanosome is involved in both DNA repair and telomeric gene silencing but is not required for antigenic variation
    Sam Alsford
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Mol Microbiol 63:724-36. 2007
    ..Antigenic variation, however, which involves the silencing and Pol I-mediated transcriptional switching of subtelomeric variant surface glycoprotein genes, continues to operate independent of SIR2rp1...
  32. pmc RNA polymerase I transcription stimulates homologous recombination in Trypanosoma brucei
    Sam Alsford
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Mol Biochem Parasitol 153:77-9. 2007
  33. ncbi request reprint Trypanosomatid histones
    Sam Alsford
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Mol Microbiol 53:365-72. 2004
    ....
  34. pmc Deletion of the Trypanosoma brucei superoxide dismutase gene sodb1 increases sensitivity to nifurtimox and benznidazole
    S Radhika Prathalingham
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    Antimicrob Agents Chemother 51:755-8. 2007
    ..Here, we identify a superoxide dismutase required to protect Trypanosoma brucei from drug-generated superoxide...
  35. ncbi request reprint The cardiac form of the tissue-specific SmN protein is identical to the brain and embryonic forms of the protein
    D Gerrelli
    Department of Biochemistry, University College and Middlesex School of Medicine, London, UK
    J Mol Cell Cardiol 25:321-9. 1993
    ..The significance of this finding is discussed in terms of the complex expression pattern of this gene and the possible functional role of SmN...
  36. pmc Tagging a T. brucei RRNA locus improves stable transfection efficiency and circumvents inducible expression position effects
    Sam Alsford
    Department of Infections and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
    Mol Biochem Parasitol 144:142-8. 2005
    ..The developments described should facilitate functional analysis and increased throughput...
  37. pmc Single-locus targeting constructs for reliable regulated RNAi and transgene expression in Trypanosoma brucei
    Sam Alsford
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Mol Biochem Parasitol 161:76-9. 2008
    ..The constructs are integrated at a single, marked locus and deliver reliable and reproducible expression...
  38. pmc Elongator protein 3b negatively regulates ribosomal DNA transcription in african trypanosomes
    Sam Alsford
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom
    Mol Cell Biol 31:1822-32. 2011
    ..ELP3b is also the first trypanosome protein shown to distinguish between rDNA and variant surface glycoprotein transcription within different RNAP-I compartments...
  39. pmc Acetylation of histone H4K4 is cell cycle regulated and mediated by HAT3 in Trypanosoma brucei
    T Nicolai Siegel
    Laboratory of Molecular Parasitology, The Rockefeller University, New York, USA
    Mol Microbiol 67:762-71. 2008
    ..As HAT3 is located inside the nucleus, our findings suggest that newly synthesized histone H4 with an unmodified K4 is imported rapidly into the nucleus, where it is acetylated, possibly irreversibly...
  40. pmc A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes
    Shane R Wilkinson
    School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom
    Proc Natl Acad Sci U S A 105:5022-7. 2008
    ..This potential for drug resistance by a simple mechanism has important implications, because nifurtimox is currently undergoing phase III clinical trials against African trypanosomiasis...
  41. ncbi request reprint A doubly inducible system for RNA interference and rapid RNAi plasmid construction in Trypanosoma brucei
    Vincent P Alibu
    Zentrum fur Molekulare Biologie der Universitat Heidelberg, ZMBH, Im Neuenheimer Feld 282, D 69120 Heidelberg, Germany
    Mol Biochem Parasitol 139:75-82. 2005
    ....
  42. ncbi request reprint The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease
    Najib M El-Sayed
    Department of Parasite Genomics, Institute for Genomic Research, Rockville, MD 20850, USA
    Science 309:409-15. 2005
    ....
  43. ncbi request reprint Analysis of small GTPase function in trypanosomes
    Mark C Field
    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Methods Enzymol 438:57-76. 2008
    ....
  44. ncbi request reprint Down-regulating gene expression by RNA interference in Trypanosoma brucei
    Christine E Clayton
    ZMBH, Heidelberg, Germany
    Methods Mol Biol 309:39-60. 2005
  45. pmc The genome of the kinetoplastid parasite, Leishmania major
    Alasdair C Ivens
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK
    Science 309:436-42. 2005
    ..Abundant RNA-binding proteins are encoded in the Tritryp genomes, consistent with active posttranscriptional regulation of gene expression...
  46. pmc Chromosome-wide analysis of gene function by RNA interference in the african trypanosome
    Chandra Subramaniam
    School of Biological Sciences, University of Manchester, Oxford Road, Manchester, United Kingdom
    Eukaryot Cell 5:1539-49. 2006
    ....
  47. ncbi request reprint Characterization of anthracenediones and their photoaffinity analogs
    Kai Ming Chou
    Department of Pharmacology, School of Medicine, University of Vermont, Burlington, VT 05405, USA
    Biochem Pharmacol 63:1143-7. 2002
    ....
  48. ncbi request reprint Viral photosynthetic reaction center genes and transcripts in the marine environment
    Itai Sharon
    Faculty of Biology, Technion Israel Institute of Technology, Haifa, Israel
    ISME J 1:492-501. 2007
    ..Furthermore, we show that different viral psbA genes are expressed in the environment...