trypanosoma brucei brucei

Summary

Summary: A hemoflagellate subspecies of parasitic protozoa that causes nagana in domestic and game animals in Africa. It apparently does not infect humans. It is transmitted by bites of tsetse flies (Glossina).

Top Publications

  1. pmc The transcriptome of the human pathogen Trypanosoma brucei at single-nucleotide resolution
    Nikolay G Kolev
    School of Public Health, Yale University, New Haven, Connecticut, United States of America
    PLoS Pathog 6:e1001090. 2010
  2. pmc High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome
    Sam Alsford
    London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    Genome Res 21:915-24. 2011
  3. pmc Four histone variants mark the boundaries of polycistronic transcription units in Trypanosoma brucei
    T Nicolai Siegel
    Laboratory of Molecular Parasitology, The Rockefeller University, New York, New York 10065, USA
    Genes Dev 23:1063-76. 2009
  4. pmc Spliced leader trapping reveals widespread alternative splicing patterns in the highly dynamic transcriptome of Trypanosoma brucei
    Daniel Nilsson
    Institute of Cell Biology, University of Bern, Bern, Switzerland
    PLoS Pathog 6:e1001037. 2010
  5. pmc Genome-wide analysis of mRNA abundance in two life-cycle stages of Trypanosoma brucei and identification of splicing and polyadenylation sites
    Tim Nicolai Siegel
    Laboratory of Molecular Parasitology, The Rockefeller University, New York, NY 10065, USA
    Nucleic Acids Res 38:4946-57. 2010
  6. pmc Telomeric expression sites are highly conserved in Trypanosoma brucei
    Christiane Hertz-Fowler
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom
    PLoS ONE 3:e3527. 2008
  7. ncbi The genome of the African trypanosome Trypanosoma brucei
    Matthew Berriman
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK
    Science 309:416-22. 2005
  8. pmc Heat shock causes a decrease in polysomes and the appearance of stress granules in trypanosomes independently of eIF2(alpha) phosphorylation at Thr169
    Susanne Kramer
    Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK
    J Cell Sci 121:3002-14. 2008
  9. ncbi Trypanocidal drugs: mechanisms, resistance and new targets
    Shane R Wilkinson
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, UK
    Expert Rev Mol Med 11:e31. 2009
  10. pmc Widespread variation in transcript abundance within and across developmental stages of Trypanosoma brucei
    Bryan C Jensen
    Seattle Biomedical Research Institute, 307 Westlake Ave North, Seattle, WA 98109, USA
    BMC Genomics 10:482. 2009

Detail Information

Publications282 found, 100 shown here

  1. pmc The transcriptome of the human pathogen Trypanosoma brucei at single-nucleotide resolution
    Nikolay G Kolev
    School of Public Health, Yale University, New Haven, Connecticut, United States of America
    PLoS Pathog 6:e1001090. 2010
    ..and revealed heterogeneity in pre-mRNA processing that could potentially contribute to the survival and success of the parasite population in the insect vector and the mammalian host...
  2. pmc High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome
    Sam Alsford
    London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    Genome Res 21:915-24. 2011
    ..The current data set also provides much needed genetic validation to identify new drug targets. RIT-seq represents a versatile new tool for genome-scale functional analyses and for the exploitation of genome sequence data...
  3. pmc Four histone variants mark the boundaries of polycistronic transcription units in Trypanosoma brucei
    T Nicolai Siegel
    Laboratory of Molecular Parasitology, The Rockefeller University, New York, New York 10065, USA
    Genes Dev 23:1063-76. 2009
    ....
  4. pmc Spliced leader trapping reveals widespread alternative splicing patterns in the highly dynamic transcriptome of Trypanosoma brucei
    Daniel Nilsson
    Institute of Cell Biology, University of Bern, Bern, Switzerland
    PLoS Pathog 6:e1001037. 2010
    ..The entire dataset can be accessed online at TriTrypDB or through: http://splicer.unibe.ch/...
  5. pmc Genome-wide analysis of mRNA abundance in two life-cycle stages of Trypanosoma brucei and identification of splicing and polyadenylation sites
    Tim Nicolai Siegel
    Laboratory of Molecular Parasitology, The Rockefeller University, New York, NY 10065, USA
    Nucleic Acids Res 38:4946-57. 2010
    ..Our study demonstrates the usefulness of the RNA-seq technology to study the transcriptional landscape of an organism whose genome has not been fully annotated...
  6. pmc Telomeric expression sites are highly conserved in Trypanosoma brucei
    Christiane Hertz-Fowler
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom
    PLoS ONE 3:e3527. 2008
    ..This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology...
  7. ncbi The genome of the African trypanosome Trypanosoma brucei
    Matthew Berriman
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK
    Science 309:416-22. 2005
    ..brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified...
  8. pmc Heat shock causes a decrease in polysomes and the appearance of stress granules in trypanosomes independently of eIF2(alpha) phosphorylation at Thr169
    Susanne Kramer
    Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK
    J Cell Sci 121:3002-14. 2008
    ....
  9. ncbi Trypanocidal drugs: mechanisms, resistance and new targets
    Shane R Wilkinson
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, UK
    Expert Rev Mol Med 11:e31. 2009
    ....
  10. pmc Widespread variation in transcript abundance within and across developmental stages of Trypanosoma brucei
    Bryan C Jensen
    Seattle Biomedical Research Institute, 307 Westlake Ave North, Seattle, WA 98109, USA
    BMC Genomics 10:482. 2009
    ..Trypanosomatids represent a unique case in eukaryotes in that they transcribe protein-coding genes as large polycistronic units, and rarely regulate gene expression at the level of transcription initiation...
  11. pmc The role of the 5'-3' exoribonuclease XRNA in transcriptome-wide mRNA degradation
    Theresa Manful
    Zentrum fur Molekulare Biologie der Universitat Heidelberg, DKFZ ZMBH Alliance, D69120 Heidelberg, Germany
    RNA 17:2039-47. 2011
    ....
  12. pmc Alba-domain proteins of Trypanosoma brucei are cytoplasmic RNA-binding proteins that interact with the translation machinery
    Jan Mani
    Institute of Cell Biology, University of Bern, Bern, Switzerland
    PLoS ONE 6:e22463. 2011
    ..Our results are also consistent with stage-specific regulation of translation in trypanosomes, but most likely in the context of initiation...
  13. pmc Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species
    Andrew P Jackson
    Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom
    Proc Natl Acad Sci U S A 109:3416-21. 2012
    ....
  14. pmc Comparative SILAC proteomic analysis of Trypanosoma brucei bloodstream and procyclic lifecycle stages
    Michael D Urbaniak
    Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee, United Kingdom
    PLoS ONE 7:e36619. 2012
    ..Our proteomic data is broadly in agreement with transcriptomic studies, but with significantly larger fold changes observed at the protein level than at the mRNA level...
  15. ncbi The structure, biosynthesis and functions of glycosylphosphatidylinositol anchors, and the contributions of trypanosome research
    M A Ferguson
    Division of Molecular Parasitology and Biological Chemistry, Department of Biochemistry, The Wellcome Trust Building, University of Dundee, Dundee DD1 5EH, UK
    J Cell Sci 112:2799-809. 1999
    ..Apart from providing stable membrane anchorage, GPI anchors have been implicated in the sequestration of GPI-anchored proteins into specialised membrane microdomains, known as lipid rafts, and in signal transduction events...
  16. pmc Functional genomics in Trypanosoma brucei: a collection of vectors for the expression of tagged proteins from endogenous and ectopic gene loci
    Steven Kelly
    Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK
    Mol Biochem Parasitol 154:103-9. 2007
  17. pmc RAP1 is essential for silencing telomeric variant surface glycoprotein genes in Trypanosoma brucei
    Xiaofeng Yang
    Department of Biological, Geological, and Environmental Sciences, Center for Gene Regulation in Health and Diseases, Cleveland State University, Cleveland, OH 44115, USA
    Cell 137:99-109. 2009
    ..This graduated silencing pattern suggests that telomere integrity plays a key role in tbRAP1-dependent silencing and VSG regulation...
  18. ncbi Sleeping sickness
    D Malvy
    Travel Clinics and Division of Tropical Medicine and Imported Diseases, Department of Internal Medicine and Tropical Diseases, University Hospital Centre, Bordeaux, France
    Clin Microbiol Infect 17:986-95. 2011
    ..New methods to diagnose and treat patients and to control transmission by the tsetse fly are needed to achieve the goal of global elimination of the disease...
  19. pmc Identification of the meiotic life cycle stage of Trypanosoma brucei in the tsetse fly
    Lori Peacock
    School of Biological Sciences, University of Bristol, Bristol BS8 1UG, United Kingdom
    Proc Natl Acad Sci U S A 108:3671-6. 2011
    ..This is evidence of conventional meiotic division in an excavate protist, and the functional conservation of the meiotic machinery in these divergent organisms underlines the ubiquity and basal evolution of meiosis in eukaryotes...
  20. pmc The cell biology of Trypanosoma brucei differentiation
    Katelyn Fenn
    Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Ashworth Laboratories, King s Buildings, West Mains Road, Edinburgh EH9 3JT, UK
    Curr Opin Microbiol 10:539-46. 2007
    ..Interestingly, the new molecular discoveries provide insights into the biology of the parasite in the field...
  21. pmc Ubiquitylation and developmental regulation of invariant surface protein expression in trypanosomes
    Ka Fai Leung
    Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, United Kingdom
    Eukaryot Cell 10:916-31. 2011
    ..We suggest that ubiquitylation may be a general mechanism for regulating trans-membrane domain surface proteins in trypanosomes...
  22. pmc The small chromosomes of Trypanosoma brucei involved in antigenic variation are constructed around repetitive palindromes
    Bill Wickstead
    Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, United Kingdom
    Genome Res 14:1014-24. 2004
    ..Moreover, palindromy appears to be a feature of (peri)centromeres in other species that can be easily overlooked. We propose that sequence inversion is one of the higher-order sequence motifs that confer chromosomal stability...
  23. ncbi Flagellar motility is required for the viability of the bloodstream trypanosome
    Richard Broadhead
    Department of Biological Sciences, Lancaster University, Lancaster LA1 4YQ, UK
    Nature 440:224-7. 2006
    ..A postgenomic meta-analysis, comparing the evolutionarily ancient trypanosome with other eukaryotes including humans, identifies numerous trypanosome-specific flagellar proteins, suggesting new avenues for selective intervention...
  24. pmc Gene expression in Trypanosoma brucei: lessons from high-throughput RNA sequencing
    T Nicolai Siegel
    Biology of Host Parasite Interactions, Parasitology, Institut Pasteur, 75724 Paris, France
    Trends Parasitol 27:434-41. 2011
    ..brucei...
  25. pmc NLP is a novel transcription regulator involved in VSG expression site control in Trypanosoma brucei
    Mani Shankar Narayanan
    Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, South Kensington, London SW7 2AZ, UK
    Nucleic Acids Res 39:2018-31. 2011
    ..Discovery of the unusual transcription regulator NLP provides new insight into the factors that are critical for ES control...
  26. pmc The FACT subunit TbSpt16 is involved in cell cycle specific control of VSG expression sites in Trypanosoma brucei
    Viola Denninger
    Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College, South Kensington, London SW72AZ, UK
    Mol Microbiol 78:459-74. 2010
    ..The chromatin remodeler FACT is therefore implicated in maintenance of repressed chromatin present at silent VSG ES promoters, but is also essential for chromosome segregation presumably through maintenance of functional centromeres...
  27. ncbi Conserved and specific functions of axoneme components in trypanosome motility
    Carole Branche
    INSERM U565 and CNRS UMR5153 and MNHN USM0503, Museum national d histoire naturelle, 43 rue Cuvier, 75231 Paris Cedex 05, France
    J Cell Sci 119:3443-55. 2006
    ..Finally, our study also reveals the conservation of molecular components of the trypanosome flagellum. Coupled to the ease of reverse genetics, it raises the interest of trypanosomes as model organisms to study cilia and flagella...
  28. pmc Chemical validation of trypanothione synthetase: a potential drug target for human trypanosomiasis
    Leah S Torrie
    Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom
    J Biol Chem 284:36137-45. 2009
    ..Taken together, these data provide initial chemical validation of TryS as a drug target in T. brucei...
  29. pmc Investigation of trypanothione reductase as a drug target in Trypanosoma brucei
    Daniel Spinks
    Drug Discovery Unit, College of Life Sciences, University of Dundee, Sir James Black Centre, Dundee, DD1 5EH, UK
    ChemMedChem 4:2060-9. 2009
    ..Both of these series, containing either a quinoline or pyrimidinopyrazine scaffold, yielded low micromolar inhibitors of the enzyme and growth of the parasite. The challenges of inhibiting TryR with druglike molecules is discussed...
  30. pmc A yeast-endonuclease-generated DNA break induces antigenic switching in Trypanosoma brucei
    Catharine E Boothroyd
    Laboratory of Lymphocyte Biology, The Rockefeller University, New York, New York 10065, USA
    Nature 459:278-81. 2009
    ....
  31. ncbi 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
    ....
  32. pmc Three-dimensional cellular architecture of the flagellar pocket and associated cytoskeleton in trypanosomes revealed by electron microscope tomography
    Sylvain Lacomble
    Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK
    J Cell Sci 122:1081-90. 2009
    ..Overall, our studies reveal a highly organised, yet dynamic, area of cytoplasm and will be informative in understanding its function...
  33. pmc The phosphoproteome of bloodstream form Trypanosoma brucei, causative agent of African sleeping sickness
    Isabelle R E Nett
    Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom
    Mol Cell Proteomics 8:1527-38. 2009
    ....
  34. ncbi The trypanosome flagellar pocket
    Mark C Field
    Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, UK
    Nat Rev Microbiol 7:775-86. 2009
    ..In this Review we discuss the contribution of the flagellar pocket to protein trafficking, immune evasion and other processes...
  35. pmc N-myristoyltransferase inhibitors as new leads to treat sleeping sickness
    Julie A Frearson
    Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, UK
    Nature 464:728-32. 2010
    ..Our studies validate T. brucei N-myristoyltransferase as a promising therapeutic target for human African trypanosomiasis...
  36. 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
    ....
  37. pmc A novel phosphatase cascade regulates differentiation in Trypanosoma brucei via a glycosomal signaling pathway
    Balázs Szöor
    Centre for Immunity, Infection, and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom
    Genes Dev 24:1306-16. 2010
    ..This is the first characterized environmental signaling pathway targeted directly to a peroxisome-like organelle in any eukaryotic cell...
  38. ncbi Assembly of the flagellum and its role in cell morphogenesis in Trypanosoma brucei
    Sue Vaughan
    School of Life Sciences, Oxford Brookes University, Gipsy Lane, Oxford OX3 0BP, UK
    Curr Opin Microbiol 13:453-8. 2010
    ..In this review we discuss evidence published in the past four years that is unravelling the role of the flagellum in organelle segregation, inheritance of cell shape and cytokinesis...
  39. pmc Nuclear DBF-2-related kinases are essential regulators of cytokinesis in bloodstream stage Trypanosoma brucei
    Jiangtao Ma
    Division of Infection and Immunity, Faculty of Biomedical and Life Sciences and Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, Glasgow G12 8QQ, Scotland, UK
    J Biol Chem 285:15356-68. 2010
    ....
  40. pmc Identification of a κ-opioid agonist as a potent and selective lead for drug development against human African trypanosomiasis
    Deuan C Jones
    Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    Biochem Pharmacol 80:1478-86. 2010
    ..Among the other potent, but less selective screening hits were compound classes with activity against protein kinases, topoisomerases, tubulin, as well as DNA and energy metabolism...
  41. pmc A molecular mechanism for eflornithine resistance in African trypanosomes
    Isabel M Vincent
    University of Glasgow, Glasgow, UK
    PLoS Pathog 6:e1001204. 2010
    ..The loss of this transporter will be easily identified in the field using a simple PCR test, enabling more appropriate chemotherapy to be administered...
  42. ncbi Metabolic functions of glycosomes in trypanosomatids
    Paul A M Michels
    Research Unit for Tropical Diseases, Christian de Duve Institute of Cellular Pathology and Laboratory of Biochemistry, Universite Catholique de Louvain, ICP TROP 74 39, Avenue Hippocrate 74, B 1200 Brussels, Belgium
    Biochim Biophys Acta 1763:1463-77. 2006
    ..The compartmentation of environment-sensitive parts of the metabolic network within glycosomes would, through this way of organelle renewal, enable the parasites to adapt rapidly and efficiently to the new conditions...
  43. 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...
  44. pmc Characterization of Trypanosoma brucei dihydroorotate dehydrogenase as a possible drug target; structural, kinetic and RNAi studies
    Tracy L Arakaki
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Mol Microbiol 68:37-50. 2008
    ..brucei enzyme, which is reported here at a resolution of 1.95 A. Additional research, guided by the crystal structure described herein, is needed to identify potent inhibitors of T. brucei DHODH...
  45. pmc Rab28 function in trypanosomes: interactions with retromer and ESCRT pathways
    Jennifer H Lumb
    Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK
    J Cell Sci 124:3771-83. 2011
    ..We suggest that Rab28 coordinates the activity of retromer-dependent trafficking and ESCRT-mediated degradative pathways...
  46. pmc Genetic control of resistance to Trypanosoma brucei brucei infection in mice
    Matyáš Síma
    Laboratory of Molecular and Cellular Immunology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    PLoS Negl Trop Dis 5:e1173. 2011
    b>Trypanosoma brucei brucei infects livestock, with severe effects in horses and dogs. Mouse strains differ greatly in susceptibility to this parasite. However, no genes controlling these differences were mapped.
  47. pmc TbISWI regulates multiple polymerase I (Pol I)-transcribed loci and is present at Pol II transcription boundaries in Trypanosoma brucei
    Tara M Stanne
    Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London South Kensington, Imperial College Road, London, United Kingdom
    Eukaryot Cell 10:964-76. 2011
    ..Our results indicate that TbISWI is a versatile chromatin remodeler that regulates transcription at multiple Pol I loci and is particularly abundant at many Pol II transcription boundaries in T. brucei...
  48. pmc Identification of Trypanosoma brucei RMI1/BLAP75 homologue and its roles in antigenic variation
    Hee Sook Kim
    Laboratory of Molecular Parasitology, The Rockefeller University, New York, New York, United States of America
    PLoS ONE 6:e25313. 2011
    ....
  49. pmc Casein kinase 1 isoform 2 is essential for bloodstream form Trypanosoma brucei
    Michael D Urbaniak
    Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Mol Biochem Parasitol 166:183-5. 2009
    ..These data show that TbCK1.2 is an attractive target for anti-trypanosomal drug discovery...
  50. pmc A protein-protein interaction map of trypanosome ~20S editosomes
    Achim Schnaufer
    Seattle Biomedical Research Institute, Seattle, Washington 98109, USA
    J Biol Chem 285:5282-95. 2010
    ..These results reveal a physical organization that underlies the coordination of the various catalytic and substrate binding activities within the ~20S editosomes during the editing process...
  51. pmc Compartmentation prevents a lethal turbo-explosion of glycolysis in trypanosomes
    Jurgen R Haanstra
    Department of Molecular Cell Physiology, Faculty of Earth and Life Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1085, NL 1081 HV, Amsterdam, The Netherlands
    Proc Natl Acad Sci U S A 105:17718-23. 2008
    ..This provides the first experimental support for our hypothesis that pathway compartmentation is an alternative to allosteric regulation...
  52. pmc Genome-wide in silico screen for CCCH-type zinc finger proteins of Trypanosoma brucei, Trypanosoma cruzi and Leishmania major
    Susanne Kramer
    Department of Biochemistry, University of Cambridge, Cambridge, UK
    BMC Genomics 11:283. 2010
    ..In kinetoplastids, CCCH type zinc finger proteins have been identified as being involved in the regulation of the life cycle and possibly the cell cycle. To date, no systematic listing of CCCH proteins in kinetoplastids is available...
  53. ncbi A vector series for rapid PCR-mediated C-terminal in situ tagging of Trypanosoma brucei genes
    Michael Oberholzer
    Institute of Cell Biology, University of Bern, Baltzerstrasse 4, CH 3012 Bern, Switzerland
    Mol Biochem Parasitol 145:117-20. 2006
  54. 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...
  55. pmc TOPO3alpha influences antigenic variation by monitoring expression-site-associated VSG switching in Trypanosoma brucei
    Hee Sook Kim
    Laboratory of Molecular Parasitology, The Rockefeller University, New York, New York, United States of America
    PLoS Pathog 6:e1000992. 2010
    ..Our data suggest that TOPO3alpha may remove undesirable recombination intermediates constantly arising between active and silent ESs, thereby balancing ES integrity against VSG recombination...
  56. ncbi Comparative genomics of trypanosomatid parasitic protozoa
    Najib M El-Sayed
    Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850, USA
    Science 309:404-9. 2005
    ..Contrary to recent reports, our analyses reveal no evidence that these species are descended from an ancestor that contained a photosynthetic endosymbiont...
  57. ncbi Asymmetric cell division as a route to reduction in cell length and change in cell morphology in trypanosomes
    Reuben Sharma
    Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK
    Protist 159:137-51. 2008
    ..Thus, the asymmetric cell division cycle provides a mechanism for a change in cell morphology and also an explanation for how a reduction in cell length can occur in a cell shaped by a stable microtubule array...
  58. ncbi 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...
  59. ncbi Human infectivity trait in Trypanosoma brucei: stability, heritability and relationship to sra expression
    C M R Turner
    Division of Infection and Immunity, Institute of Biomedical and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow, G12 8QQ, UK
    Parasitology 129:445-54. 2004
    ....
  60. 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...
  61. ncbi Expression and role of CXCL10 during the encephalitic stage of experimental and clinical African trypanosomiasis
    Daniel N Amin
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
    J Infect Dis 200:1556-65. 2009
    ..Human African trypanosomiasis, caused by Trypanosoma brucei, involves an early hemolymphatic stage followed by a late encephalitic stage...
  62. ncbi Migration of African trypanosomes across the blood-brain barrier
    Willias Masocha
    Karolinska Institutet, Department of Neuroscience, S 171 77 Stockholm, Sweden
    Physiol Behav 92:110-4. 2007
    ....
  63. 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...
  64. pmc Glycolysis modulates trypanosome glycoprotein expression as revealed by an RNAi library
    James C Morris
    Department of Biological Chemistry, Johns Hopkins Medical School, 725 N Wolfe Street, Baltimore, MD 21205, USA
    EMBO J 21:4429-38. 2002
    ..These data suggest that T.brucei 'senses' changes in glucose level and modulates procyclin expression accordingly...
  65. ncbi The suppression of galactose metabolism in procylic form Trypanosoma brucei causes cessation of cell growth and alters procyclin glycoprotein structure and copy number
    Janine R Roper
    Division of Biological Chemistry and Molecular Microbiology, The School of Life Sciences, University of Dundee, Scotland, UK
    J Biol Chem 280:19728-36. 2005
    ..The parasites compensated, ultimately unsuccessfully, by expressing 10-fold more procyclin. The implications of these data with respect to the relative roles of procyclin polypeptide and carbohydrate are discussed...
  66. pmc Differential trypanosome surface coat regulation by a CCCH protein that co-associates with procyclin mRNA cis-elements
    Pegine Walrad
    Centre for Immunology, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, Ashworth Laboratories, University of Edinburgh, Edinburgh, UK
    PLoS Pathog 5:e1000317. 2009
    ..Combined with the known association of TbZFP3 with the translational apparatus, this study provides a long-sought missing link between surface protein cis-regulatory signals and the gene expression machinery in trypanosomes...
  67. ncbi Molecular diagnostics for sleeping sickness: what is the benefit for the patient?
    Stijn Deborggraeve
    Department of Parasitology, Institute of Tropical Medicine, Antwerp, Belgium
    Lancet Infect Dis 10:433-9. 2010
    ..The current formats are not applicable to field conditions, and simplification, standardisation, and proper test evaluation in the target setting should be the main focus for future development...
  68. ncbi Intraspecific competition between co-infecting parasite strains enhances host survival in African trypanosomes
    Oliver Balmer
    Department of Ecology and Evolutionary Biology, Yale University, 165 Prospect Street, New Haven, Connecticut 06511, USA
    Ecology 90:3367-78. 2009
    ..Our results are therefore not only of basic ecological interest investigating an important form of intraspecific competition, but may also have applied relevance for public health...
  69. ncbi Ubiquitylation is required for degradation of transmembrane surface proteins in trypanosomes
    Wei Lian Chung
    Department of Pathology, University of Cambridge, Cambridge, UK
    Traffic 9:1681-97. 2008
    ..Hence, ubiquitylation is an evolutionarily conserved mechanism for internalization of surface proteins, but aspects of the machinery differ substantially between the major eukaryotic lineages...
  70. pmc Trypanosoma brucei glycogen synthase kinase-3, a target for anti-trypanosomal drug development: a public-private partnership to identify novel leads
    Richard O Oduor
    Opportunities for Partnering in Medicine, Pfizer Global Research and Development, Sandwich, Kent, United Kingdom
    PLoS Negl Trop Dis 5:e1017. 2011
    ..A collaborative industrial/academic partnership facilitated by the World Health Organisation Tropical Diseases Research division (WHO TDR) was initiated to stimulate research aimed at identifying new drugs for treating HAT...
  71. pmc The distribution of nifurtimox across the healthy and trypanosome-infected murine blood-brain and blood-cerebrospinal fluid barriers
    Sinthujah Jeganathan
    Pharmaceutical Sciences Research Division, King s College London, London, United Kingdom
    J Pharmacol Exp Ther 336:506-15. 2011
    ..Consequently, CNS efficacy may be improved with nifurtimox-pentamidine combinations, but over time may be reduced when nifurtimox is combined with eflornithine, suramin, or melarsoprol...
  72. pmc High affinity nanobodies against the Trypanosome brucei VSG are potent trypanolytic agents that block endocytosis
    Benoit Stijlemans
    Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussels, Brussels, Belgium
    PLoS Pathog 7:e1002072. 2011
    ....
  73. pmc Independent analysis of the flagellum surface and matrix proteomes provides insight into flagellum signaling in mammalian-infectious Trypanosoma brucei
    Michael Oberholzer
    Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA
    Mol Cell Proteomics 10:M111.010538. 2011
    ..The combined results indicate that the flagellum surface presents a diverse and dynamic host-parasite interface that is well-suited for host-parasite signaling...
  74. ncbi Development of novel drugs for human African trypanosomiasis
    Reto Brun
    Department Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and, University of Basel, CH 4002 Basel, Switzerland
    Future Microbiol 6:677-91. 2011
    ..With other screening programs yielding hits, the pipeline for new HAT drugs might finally begin to fill...
  75. ncbi Characterization of tGLP-1, a Golgi and lysosome-associated, transmembrane glycoprotein of African trypanosomes
    A Lingnau
    Washington University School of Medicine, Department of Molecular Microbiology, St Louis, MO 63110, USA
    J Cell Sci 112:3061-70. 1999
    Purification of endosomal/lysosomal vesicles of Trypanosoma brucei brucei bloodstream forms and generation of monoclonal antibodies led to the isolation of antibodies directed against an 85 kDa, Golgi and endocytic traffic-associated ..
  76. pmc Endonuclease associations with three distinct editosomes in Trypanosoma brucei
    Jason Carnes
    Seattle Biomedical Research Institute, Seattle, Washington 98109, USA
    J Biol Chem 286:19320-30. 2011
    ..These results and published data suggest that KREPB6, KREPB7, and KREPB8 associate with the deletion subcomplex, whereas the KREN1, KREN2, and KREN3 endonucleases associate with the insertion subcomplex...
  77. pmc Chaperone requirements for biosynthesis of the trypanosome variant surface glycoprotein
    Mark C Field
    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    PLoS ONE 5:e8468. 2010
    ..As the variant surface glycoprotein (VSG) represents approximately 90% of trypanosome plasma membrane protein, it is possible that VSG has evolved to fold efficiently to minimize ER folding burden...
  78. ncbi Transposon mutagenesis of Trypanosoma brucei identifies glycosylation mutants resistant to concanavalin A
    Simone Leal
    Laboratory of Molecular Parasitology, The Rockefeller University, New York, New York 10021, USA
    J Biol Chem 279:28979-88. 2004
    ..25%. As we approach the completion of the trypanosome genome project, transposon mutagenesis provides an important addition to the repertoire of genetic tools for T. brucei...
  79. pmc Transmission stages dominate trypanosome within-host dynamics during chronic infections
    Paula MacGregor
    Centre for Immunity, Infection, and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK
    Cell Host Microbe 9:310-8. 2011
    ..Our data reveal the dominance of transmission stages throughout infection, a consequence being austere use of the parasite's antigen repertoire...
  80. ncbi Nuclear architecture, genome and chromatin organisation in Trypanosoma brucei
    Klaus Ersfeld
    Department of Biological Sciences and Hull York Medical School, University of Hull, Hull HU6 7RX, UK
    Res Microbiol 162:626-36. 2011
    ..These advances also have a major impact on progress in understanding the molecular basis of antigenic variation...
  81. ncbi Mitochondrial preprotein translocase of trypanosomatids has a bacterial origin
    Mascha Pusnik
    Department of Chemistry and Biochemistry, University of Bern, CH 3012 Bern, Switzerland
    Curr Biol 21:1738-43. 2011
    ..This suggests that the protein import channel in trypanosomes is a relic of an archaic protein transport system that was operational in the ancestor of all eukaryotes...
  82. pmc A zinc finger protein, TbZC3H20, stabilizes two developmentally regulated mRNAs in trypanosomes
    Alexandra S Ling
    Division of Cell and Molecular Biology, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom
    J Biol Chem 286:20152-62. 2011
    ..This suggests a broader role for ZC3Hs in post-transcriptional regulation of gene expression than previously thought...
  83. pmc Dissecting the essentiality of the bifunctional trypanothione synthetase-amidase in Trypanosoma brucei using chemical and genetic methods
    Susan Wyllie
    Division of Biological Chemistry and Drug Discovery, Wellcome Trust Biocentre, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, Scotland, UK
    Mol Microbiol 74:529-40. 2009
    ..The synthetase function of TRYS is thus unequivocally validated as a drug target by both chemical and genetic methods...
  84. pmc Cohesin regulates VSG monoallelic expression in trypanosomes
    David Landeira
    Instituto de Parasitologia y Biomedicina Lopez Neyra, Consejo Superior de Investigaciones Cientificas, 18100 Granada, Spain
    J Cell Biol 186:243-54. 2009
    ..Thus, in addition to maintaining sister chromatid cohesion during mitosis, the cohesin complex plays an essential role in the correct epigenetic inheritance of the active transcriptional VSG ES state...
  85. pmc Comparative genomics reveals two novel RNAi factors in Trypanosoma brucei and provides insight into the core machinery
    Rebecca L Barnes
    Department of Internal Medicine, Yale University, New Haven, Connecticut, USA
    PLoS Pathog 8:e1002678. 2012
    ..The availability of the core RNAi machinery in T. brucei provides a platform to gain mechanistic insights in this ancient eukaryote and to identify the minimal set of components required to reconstitute RNAi in RNAi-deficient parasites...
  86. ncbi Structural analysis of the asparagine-linked glycans from the procyclic Trypanosoma brucei and its glycosylation mutants resistant to Concanavalin A killing
    K Y Hwa
    Institute of Biological Chemistry, Academia Sinica, 128 Yen Chiu Yuan Road, Section 2, Nankang, Taipei, 115, Taiwan, ROC
    Mol Biochem Parasitol 111:173-84. 2000
    ....
  87. ncbi Partial biochemical characterization of a metalloproteinase from the bloodstream forms of Trypanosoma brucei brucei parasites
    Karina Pires de Sousa
    Unidade de Ensino e Investigação de Clínica das Doenças Tropicais, Centro de Malaria e Outras Doencas Tropicais, Instituto de Higiene e Medicina Tropical, Rua da Junqueira, Lisbon, Portugal
    Protein J 29:283-9. 2010
    ..the proteolytic activity of the crude trypanosome protein extract obtained from the bloodstream forms of Trypanosoma brucei brucei parasites...
  88. ncbi The Trypanosoma brucei autoantigen I/6 is an internally repetitive cytoskeletal protein
    E Detmer
    Institut fur Allgemeine Mikrobiologie, Universitat Bern, Switzerland
    Eur J Cell Biol 72:378-84. 1997
    ..Protein I/6 contains a non-functional EF-hand calcium binding domain and a domain of six tandemly arranged repeat units of eight amino acids length...
  89. pmc Exportin 1 mediates nuclear export of the kinetoplastid spliced leader RNA
    Gusti M Zeiner
    Department of Microbiology, University of California at Los Angeles, Los Angeles, California 90095 1489, USA
    Eukaryot Cell 2:222-30. 2003
    ..This study demonstrates spatial and mechanistic similarities between the posttranscriptional trafficking of the kinetoplastid protozoan SL RNA and the metazoan cis-spliceosomal small nuclear RNAs...
  90. pmc The Cdc45·Mcm2-7·GINS protein complex in trypanosomes regulates DNA replication and interacts with two Orc1-like proteins in the origin recognition complex
    Hung Quang Dang
    Department of Microbiology and Molecular Genetics, University of Texas Medical School, Houston, Texas 77030, USA
    J Biol Chem 286:32424-35. 2011
    ..All together, we identified the Cdc45·Mcm2-7·GINS complex as the replicative helicase that interacts with two Orc1-like proteins in the unusual origin recognition complex in trypanosomes...
  91. pmc The 3' untranslated region of the hsp 70 genes maintains the level of steady state mRNA in Trypanosoma brucei upon heat shock
    M G Lee
    Department of Pathology, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA
    Nucleic Acids Res 26:4025-33. 1998
    ....
  92. ncbi Altering the reaction specificity of eukaryotic ornithine decarboxylase
    L K Jackson
    Department of Pharmacology and Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390 9041, USA
    Biochemistry 39:11247-57. 2000
    ..The results further provide insight into the mechanism by which this class of PLP-dependent enzymes controls reaction specificity...
  93. pmc Pentatricopeptide repeat proteins stimulate mRNA adenylation/uridylation to activate mitochondrial translation in trypanosomes
    Inna Aphasizheva
    Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA
    Mol Cell 42:106-17. 2011
    ..Furthermore, we demonstrate that A/U-tailed mRNA preferentially interacts with the small ribosomal subunit, whereas edited substrates and complexes bind to the large subunit...
  94. pmc Pentamidine movement across the murine blood-brain and blood-cerebrospinal fluid barriers: effect of trypanosome infection, combination therapy, P-glycoprotein, and multidrug resistance-associated protein
    Lisa Sanderson
    King s College London, Pharmaceutical Sciences Research Division, Hodgkin Building, Guy s Campus, London, SE1 1UL, UK
    J Pharmacol Exp Ther 329:967-77. 2009
    ..However, coadministration of P-glycoprotein and/or MRP inhibitors with pentamidine or other diamidines might provide a means of improving efficacy against CNS stage HAT...
  95. pmc Temporal order of RNA-processing reactions in trypanosomes: rapid trans splicing precedes polyadenylation of newly synthesized tubulin transcripts
    E Ullu
    Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510 8056
    Mol Cell Biol 13:720-5. 1993
    ..Thus, trans splicing is cotranscriptional. In addition, we show that trans splicing precedes polyadenylation in the processing of trypanosome tubulin pre-mRNAs...
  96. ncbi Perturbation of phosphatidylethanolamine synthesis affects mitochondrial morphology and cell-cycle progression in procyclic-form Trypanosoma brucei
    Aita Signorell
    Institute of Biochemistry and Molecular Medicine, University of Bern, 3012 Bern, Switzerland
    Mol Microbiol 72:1068-79. 2009
    ..In contrast, RNAi against choline-/ethanolamine phosphotransferase, which affected PC as well as PE levels, caused a cell division phenotype characterized by non-division of the nucleus and production of zoids...
  97. pmc Functional characterization of three leishmania poly(a) binding protein homologues with distinct binding properties to RNA and protein partners
    Tamara D da Costa Lima
    Departamento de Microbiologia, Centro de Pesquisas Aggeu Magalhaes FIOCRUZ, Recife, PE, Brazil
    Eukaryot Cell 9:1484-94. 2010
    ..Our results indicate that these homologues have evolved divergent functions, some of which may be unique to the trypanosomatids, and reinforces a role for LmPABP1 in translation through its interaction with the eIF4G homologue...
  98. ncbi The trypanolytic factor-mechanism, impacts and applications
    Richard J Wheeler
    Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, UK
    Trends Parasitol 26:457-64. 2010
    ..b. brucei and T. b. rhodesiense. This has major implications for treatment and prevention of human and animal African trypanosomiasis...
  99. pmc Histone H3 trimethylated at lysine 4 is enriched at probable transcription start sites in Trypanosoma brucei
    Jessica R Wright
    Laboratory of Molecular Parasitology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
    Mol Biochem Parasitol 172:141-4. 2010
    ..H3K4me3 largely co-localizes with H4K10ac, but with a skew towards the upstream side of the H4K10ac peak, suggesting that it is a component of specific nucleosomes that play a role in Pol II transcription initiation...
  100. pmc Defects in the N-linked oligosaccharide biosynthetic pathway in a Trypanosoma brucei glycosylation mutant
    Alvaro Acosta-Serrano
    Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA
    Eukaryot Cell 3:255-63. 2004
    ..The smaller OSL glycan in the ConA 1-1 explains how some procyclin polypeptides bear a Man4GlcNAc2 modified with a terminal N-acetyllactosamine group, which is poorly recognized by ConA...
  101. pmc Small nucleolar RNA interference in Trypanosoma brucei: mechanism and utilization for elucidating the function of snoRNAs
    Sachin Kumar Gupta
    The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar Ilan University, Ramat Gan 52900 Israel
    Nucleic Acids Res 38:7236-47. 2010
    ..snoRNAi of TB11Cs2C2 resulted in defects in generating srRNA-2 and LSUβ rRNA. This is the first snoRNA described so far to engage in trypanosome-specific processing events...

Research Grants64

  1. Mechanisms of Resistance and Susceptibility to African Trypanosome Infection
    Stephen L Hajduk; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Trypanosoma brucei brucei causes Nagana in cattle but is non-infectious to humans because of its susceptibility to the cytotoxic activity of normal human serum...
  2. Mechanism of membrane permeabilization by a cytolytic high density lipoprotein
    JOHN MATTHEW HARRINGTON; Fiscal Year: 2010
    Humans exhibit an innate immunity against the mammalian parasite Trypanosoma brucei brucei, the causative agent of Nagana in African cattle. The morphologically indistinct T. brucei subspecies T. b. rhodesiense and T. b...
  3. Origin of Virulence Factors in African Trypanosomes
    ANDREW MCARTHUR; Fiscal Year: 2004
    ..brucei rhodesiense are protozoan parasites that cause African sleeping sickness in humans while Trypanosoma brucei brucei causes a wasting disease in cattle called Nagana...
  4. MITOCHONDRIAL ELECTRON TRANSPORT IN AFRICAN TRYPANOSOMES
    ALLEN CLARKSON JR; Fiscal Year: 1993
    ..b>Trypanosoma brucei brucei will be used as a model to achieve two primary objectives...
  5. LYSIS OF TRYPANOSOMA BRUCEI BY HUMAN SERUM
    Stephen Tomlinson; Fiscal Year: 2000
    b>Trypanosoma brucei brucei, unlike the human pathogens Tau beta rhodesiense and Tau gambiense, is lysed by human serum...
  6. APOLIPOPROTEIN E ALLELES IN MODULATING TRYPANOSOMA
    George Martin; Fiscal Year: 2001
    ..In this proposal, we test a specific candidate organism, Trypanosoma brucei brucei, a protozoan that is the cause of endemic infections in many regions of Africa and is associated with a ..
  7. Zinc metalloprotease families in Trypansoma brucei
    JOHN DONELSON; Fiscal Year: 2009
    ....
  8. Software tools for analysis and visulaization of protein structure
    Ethan A Merritt; Fiscal Year: 2010
    ..The algorithms and computation tools developed as part of this work will be distributed freely, and we will provide web-based state of the art analysis of structures submitted by external researchers. ..
  9. MITOCHONDRIAL PROTEIN IMPORT IN AFRICAN TRYPANOSOMES
    Minu Chaudhuri; Fiscal Year: 2002
    ..Understanding of this developmental process will elucidate one of the major aspects of trypanosomal parasitism. This in turn will help us to design rational trypanocidal chemotherapeutic strategies. ..
  10. EXPANDED PROTEIN STRUCTURE REFINEMENT AND VALIDATION
    Ethan Merritt; Fiscal Year: 2005
    ..This, in turn, will make it easier to identify key biological features such as the presence and conformation of bound ligands, and the nature of hinge and inter-domain motions. ..
  11. AMASTIN/TUZIN GENE CLUSTER OF TRYPANOSOMA CRUZI
    JOHN DONELSON; Fiscal Year: 2001
    ..Finally, we will assess whether amastin and/or tuzin can serve a target antigens for an improved diagnostic test for T. cruzi infection. ..
  12. GP46 GENES AND PROTEIN EXPRESSION IN LEISHMANIA CHAGASI
    JOHN DONELSON; Fiscal Year: 2002
    ....
  13. Targeting Calpain for Novel Anticancer Agents
    ISAAC DONKOR; Fiscal Year: 2005
    ..Additionally, the compounds are useful biomedical tools for investigating the intracellular roles of Calpain due to their metabolic stability. The compounds are also potential anticancer agents. ..
  14. RNA METABOLISM IN TRYPANOSOMES
    Elisabetta Ullu; Fiscal Year: 2009
    ..3. Further characterize the RNAi pathway in terms of its components and how the interaction of TbAGO1 with translating ribosomes is brought about. ..
  15. DEVELOPMENT OF GENETIC TOOLS FOR TRYPANOSOMA BRUCEI
    GEORGE CROSS; Fiscal Year: 2006
    ..abstract_text> ..
  16. Water-Soluble and Metabolically Stable Calpain Inhibitors as Cardioprotectants
    ISAAC DONKOR; Fiscal Year: 2008
    ..Furthermore, the proposed studies will provide mechanistic insight into the mode of action of calpain inhibitors as cardioprotectants. ..
  17. Biochemical and Functional Analysis of Trypanin
    KENT HILL; Fiscal Year: 2007
    ..Therefore, in addition to addressing fundamental questions in cell biology, this research directly impacts efforts to understand and treat infectious diseases and genetic diseases in humans. ..
  18. Biology of Host-Parasite Interactions 2008 Gordon Research Conference
    Elisabetta Ullu; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  19. 2006 Biology of Host-Parasite Interactions Gordon Research Conference
    Elisabetta Ullu; Fiscal Year: 2006
    ..Host-Cell Invasion (Discussion Leader: Barbara Burleigh: Harvard) Trichomonads and Amoebae (Discussion Leader: Patricia Johnson, UCLA) Parasite Membrane Biology (Discussion Leader: Scott Landfear: University of Oregon) ..
  20. Telomere structure and function in Trypanosoma brucei
    GEORGE CROSS; Fiscal Year: 2005
    ..There are significant similarities between the telomeres of trypanosomes and humans, so trypanosomes would be a useful model in which to study events that are relevant to human aging and cancer. ..
  21. PROBING THE S' SUBSITES OF CALPAIN
    ISAAC DONKOR; Fiscal Year: 2002
    ..Selected potent and cell permeable inhibitors will be tested in the rat isolated heart ischemia model for cardioprotective effect. ..
  22. A NOVEL MICROTUBULE-ASSOCIATED PROTEIN IN TRYPANOSOMES
    KENT HILL; Fiscal Year: 2002
    ....
  23. Chemoprevention Potential of Calpain Inhibitors
    ISAAC DONKOR; Fiscal Year: 2007
    ..The proposal is significant and innovative because it seeks to investigate calpain as a pharmacological target for the discovery of a new class of chemoprevention agents. [unreadable] [unreadable] [unreadable]..
  24. RNA Uridylytransferases of Trypanosomes
    Ruslan Aphasizhev; Fiscal Year: 2009
    ..Sequences of the newly identified UTP-specific transferases will be used to establish characteristic protein motifs for this family of enzymes. ..
  25. Polyamine and glutathione metabolism in trypanosomes.
    Margaret Phillips; Fiscal Year: 2008
    ..In Aim 3 we propose to study the effects of both genetic and metabolic perturbations in the pathway on the levels of key enzymes and metabolites. ..
  26. Antigenic variation in rickettsial transmission
    Guy Palmer; Fiscal Year: 2008
    ..This hypothesis will be addressed using comprehensive identification of the variant population in the reservoir host and tick vector and testing whether immune responses against a broad array of variants prevents superinfection. ..
  27. Inhibition of Alzheimer's Beta-Amyloid Fibril Formation
    Duy Hua; Fiscal Year: 2009
    ..However, soluble oligomeric Abeta showed high neuronal toxicity. Inhibition of the formation of these toxic soluble Abeta oligomers would provide therapeutics for AD. ..
  28. Polyamine Metabolism in Leishmania
    Buddy Ullman; Fiscal Year: 2008
    ..donovani. We propose, therefore, to ascertain whether the disparity in the abilities of ?lmarg L. mexicana and ?ldodc L. donovani to infect mice can be ascribed to species or gene differences. ..
  29. GPCR signaling cascades in Cryptococcus neoformans
    Joseph Heitman; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  30. Role of Calcineurin in Fungal Virulence
    Joseph Heitman; Fiscal Year: 2009
    ..Importantly, this pathway can be targeted for therapeutic intervention using non-immunosuppressive calcineurin inhibitors that retain antifungal activity and synergistic drug combinations that we have discovered. ..
  31. Functional Characterization of Leishmania Transporters
    Scott M Landfear; Fiscal Year: 2010
    ..Overall, this proposal will provide a detailed biochemical and genetic dissection of glucose transporter function and the essential role of these permeases in the parasite life cycle. ..
  32. Genetic analysis of Cryptococcus neoformans virulence
    Joseph Heitman; Fiscal Year: 2009
    ..These studies will enable a genome-wide definition of the gene set contributing to virulence of this common human fungal pathogen. ..
  33. Transcription of protein-coding genes in Leishmania
    PETER JOHN MYLER; Fiscal Year: 2010
    ..In this proposal, we will test this hypothesis and build on our current work to further characterize the chromatin-modifying enzymes that are involved in transcription initiation. ..
  34. PROTEIN PHOSPHORYLATION IN TRYPANOSOMES
    Marilyn Parsons; Fiscal Year: 2010
    ..Together these studies will signficantly expand our knowledge of the network of signaling interactions in trypanosomes, with the goal of identifying new drug and vaccine targets. ..
  35. Structural studies on the P1 plasmid partition apparatus
    Maria Schumacher; Fiscal Year: 2009
    ....
  36. Trypansome RNA Editing in Two Developmental Forms
    Jorge Cruz Reyes; Fiscal Year: 2008
    ..Together these studies should provide important insights into the developmental control of RNA editing, and understanding of relevant RNA/protein interactions during this unique maturation process. [unreadable] [unreadable]..
  37. 2007 Polyamines Gordon Conference and Graduate Research Seminar
    Margaret Phillips; Fiscal Year: 2007
    ..abstract_text> ..
  38. Anaplasma - B. burgorferi/endothelijm interactions
    DENNIS GRAB; Fiscal Year: 2006
    ..burgdorferi. The elucidation of the steps that explain the enhancement may allow for more intensive basic and clinical investigation into mechanisms of virulence for Lyme disease, HGE, and coinfections. ..
  39. Conference on Drugs Against Protozoan Parasites
    Margaret Phillips; Fiscal Year: 2005
    ..Experts in drug development outside of parasitology have also been invited in an effort to stimulate their interests in tropical medicine and to learn from their experiences. ..
  40. GRNA/MRNA INTERACTIONS IN TRYPANSOME RNA EDITING
    DONNA KOSLOWSKY; Fiscal Year: 2005
    ..Understanding kRNA editing, which is unique to these organisms, will contribute to the fundamental knowledge of the parasite and may lead to the development of new strategies for disease intervention and control. ..
  41. Anti-Trypanosomal Agents from a Neotropical Cloudforest
    WILLIAM SETZER; Fiscal Year: 2004
    ..The long-term benefit of this research project is the development of new medicines to treat patients with Chagas disease. ..
  42. MOLECULAR ANALYSIS OF THE GLYCOSOME.
    Marilyn Parsons; Fiscal Year: 2004
    ..Their studies are aimed at understanding glycosomal biogenesis and protein input and the relationship of these processes and the molecules involved to peroxisome biogenesis in the human host. ..
  43. Adaptation of ribozyme technology to Leishmania
    NANCY STURM; Fiscal Year: 2004
    ..Once the parameters of the technique are established increasingly ambitious experiments can be designed including targeting of the spliced SL or discrete mRNAs. ..
  44. MITOCHONDRIAL RNA METABOLISM IN TRYPANOSOMA BRUCEI
    LAURIE READ; Fiscal Year: 2004
    ..Moreover, since little is known about RNA degradation in the mitochondria of any system, these studies will provide insights into the process of regulated mitochondrial RNA stability in higher organisms. ..
  45. SCAVENGER RECEPTOR OF AFRICAN TRYPANOSOMES
    Jayne Raper; Fiscal Year: 2003
    ..Raper's ability to pursue her long-term goal of elucidating trypanosome receptors and other invariant surface proteins as potential therapeutic targets. ..
  46. A CHEMICALLY SYNTHETIC ANTI-TOXIC VACCINE AGAINST MALARI
    Louis Schofield; Fiscal Year: 2002
    ..Clinical immunity to malaria is acquired considerably earlier than anti-parasite immunity, and it is possible that this is mediated by anti-toxin mechanisms. ..
  47. IMMUNOBIOLOGY OF MALARIA GLYCOSYLPHOSPHATIDYLINOSITOL
    Louis Schofield; Fiscal Year: 2001
    ..These areas are central to understanding the host/parasite interaction and the development of effective vaccines to several protozoal pathogens. ..
  48. PPR family proteins in trypanosome mitochondria
    LAURIE READ; Fiscal Year: 2006
    ..Since the functions of PPRs are not well understood in general, they will likely provide novel insights into the functions of this conserved protein family in higher organisms as well. [unreadable] [unreadable]..
  49. Golgi Architecture, Biogenesis and Function
    Elisabetta Ullu; Fiscal Year: 2007
    ..Both have a single Golgi apparatus, the duplication of which can be followed in real time using video fluorescence microscopy. These simple systems are also medically important. [unreadable] [unreadable]..
  50. GENETIC ANALYSIS OF PURINE METABOLISM IN LEISHMANIA DONO
    Buddy Ullman; Fiscal Year: 2007
    ..coli that overexpress hgprt genes, and[unreadable] intact parasites. ..
  51. Transcription and Insertional editing in Physarum
    Jonatha Gott; Fiscal Year: 2006
    ..abstract_text> ..
  52. Nucleoside Transporters of Plasmodium falciparum
    Buddy Ullman; Fiscal Year: 2007
    ..falciparum in order to test whether PfNT1 function is essential to the intact parasite. We will then characterize the resultant transport and growth phenotypes. ..
  53. R13 travel grant for Polyamine/parasite conference in Portland, OR
    Buddy Ullman; Fiscal Year: 2006
    ..abstract_text> ..
  54. MEMBRANE FUSION ATPASES AND THE GOLGI APPARATUS
    Ayano Satoh; Fiscal Year: 2007
    ..Insights into the molecular mechanism of Golgi reassembly may therefore provide insight into these medical conditions. ..
  55. MITOCHONDRIAL RNA METABOLISM IN TRYPANOSOMA BRUCEI
    LAURIE READ; Fiscal Year: 2007
    ..Proteins that specifically bind the RPS12 stabilization determinant will be identified. 3) Determine the structure and function of the mitochondrial degradosome using a combined affinity chromatography and RNAi approach. ..
  56. Genome Evolution, Innovation and Adaptation in the Apicomplexa
    Jessica C Kissinger; Fiscal Year: 2010
    ..The results of these studies will be shared with the larger research community via publication and deposition in community databases and Bioinformatics Resource Centers. ..
  57. A High Throughput Assay to Identify Onhibitors of Trypanosome RNA Editing Ligase
    Nancy Ernst; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  58. Postsynthetic Modifications of Bacterial Membrane Lipids
    John Cronan; Fiscal Year: 2006
    ..These processes will be studied by a combination of biochemical, genetic, and molecular biological approaches including tests of pathogenesis in a mouse model system ..
  59. Enzyme Targets-Sterol Synthesis-Opportunistic Pathogens
    WILLIAM NES; Fiscal Year: 2004
    ..The results from these studies will facilitate the design of therapeutic strategies aimed to provide species-specific discrimination of inhibition in the ergosterol biosynthetic pathway. ..
  60. Sir2 regulation and chemical modulation
    Anthony A Sauve; Fiscal Year: 2010
    ..abstract_text> ..
  61. Trypanosomatid Mitochondrial DNA Polymerases
    Michele Klingbeil; Fiscal Year: 2008
    ..The T. brucei pol I-like protein family also offers the unique opportunity to uncover insights into the evolutionary strategies used to produce a replicative polymerase. ..
  62. The SMD-Relaxed Complex Method for Drug Design
    Rommie Amaro; Fiscal Year: 2008
    ..The success of this new approach will be demonstrated on an essential RNA editing enzyme found in the trypanosomatid pathogens, which are responsible for several devastating tropical diseases. [unreadable] [unreadable] [unreadable]..
  63. Ecology, genetics and physiology of insect vectors
    Elliot Krafsur; Fiscal Year: 2006
    ..abstract_text> ..
  64. Topoisomerases: Target for Antitrypanosomal Therapy
    Theresa Shapiro; Fiscal Year: 2006
    ..Compounds that appear most promising will be evaluated in mice. These studies take a multi-faceted, rational, and tangible approach to the development of much-needed new anti-trypanosomal chemotherapy. ..