Sam Alsford

Summary

Affiliation: London School of Hygien & Tropical Medicine
Location: London, UK
URL: http://blogs.lshtm.ac.uk/alsfordlab/
Summary:
Lecturer in molecular biology.
Work in the lab is focused on the parasite’s interaction with its host environment, especially the uptake and sub-cellular transit of host-and parasite-derived molecules, and the consequences of such encounters for the African trypanosome.
Grants:
Characterisation of uptake and sub-cellular transit of human serum trypanolytic factors by Trypanosoma brucei, 2013, MRC

Publications

  1. 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
  2. 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
  3. 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
  4. 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
  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 NUP-1 Is a large coiled-coil nucleoskeletal protein in trypanosomes with lamin-like functions
    Kelly N DuBois
    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    PLoS Biol 10:e1001287. 2012
  7. doi request reprint Epigenetic mechanisms, nuclear architecture and the control of gene expression in trypanosomes
    Sam Alsford
    London School of Hygiene and Tropical Medicine, London, UK
    Expert Rev Mol Med 14:e13. 2012
  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 Telomeres, tethers and trypanosomes
    Mark C Field
    Department of Pathology University of Cambridge, Cambridge, UK
    Nucleus 3:478-86. 2012
  10. pmc Genetic dissection of drug resistance in trypanosomes
    Sam Alsford
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Parasitology 140:1478-91. 2013

Collaborators

Detail Information

Publications27

  1. 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...
  2. 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...
  3. 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...
  4. 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...
  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 NUP-1 Is a large coiled-coil nucleoskeletal protein in trypanosomes with lamin-like functions
    Kelly N DuBois
    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    PLoS Biol 10:e1001287. 2012
    ..Thus, analogous to vertebrate lamins, NUP-1 is a major component of the nucleoskeleton with key roles in organization of the nuclear periphery, heterochromatin, and epigenetic control of developmentally regulated loci...
  7. doi request reprint Epigenetic mechanisms, nuclear architecture and the control of gene expression in trypanosomes
    Sam Alsford
    London School of Hygiene and Tropical Medicine, London, UK
    Expert Rev Mol Med 14:e13. 2012
    ..Therefore, both evolutionarily common and novel mechanisms cohabit in trypanosomes, offering both important biological insights and possible therapeutic opportunity...
  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 Telomeres, tethers and trypanosomes
    Mark C Field
    Department of Pathology University of Cambridge, Cambridge, UK
    Nucleus 3:478-86. 2012
    ..We discuss these and other recent findings on the organization of nuclei in diverse organisms, and the implications of these findings for the evolutionary origin of eukaryotes...
  10. pmc Genetic dissection of drug resistance in trypanosomes
    Sam Alsford
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Parasitology 140:1478-91. 2013
    ..The new knowledge gained should inform the development of novel interventions against the devastating diseases caused by these parasites...
  11. 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...
  12. 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...
  13. 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...
  14. 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...
  15. ncbi request reprint A fluorescence in situ hybridisation study of the regulation of histone mRNA levels during the cell cycle of Trypanosoma brucei
    K Ersfeld
    School of Biological Sciences, University of Manchester, UK
    Mol Biochem Parasitol 81:201-9. 1996
    ....
  16. ncbi request reprint Segregation of minichromosomes in trypanosomes: implications for mitotic mechanisms
    K Gull
    School of Biological Sciences, University of Manchester, UK
    Trends Microbiol 6:319-23. 1998
    ..This minichromosomal population is segregated on the mitotic spindle. How this is achieved provides insight into potential segregation mechanisms for small DNA molecules in eukaryotic microorganisms...
  17. ncbi request reprint Diversity and dynamics of the minichromosomal karyotype in Trypanosoma brucei
    S Alsford
    School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester M13 9PT, UK
    Mol Biochem Parasitol 113:79-88. 2001
    ..This steady telomeric growth, counteracted by stochastic large losses of telomeric sequences is the most likely cause of minichromosome karyotype heterogeneity within a population...
  18. ncbi request reprint The identification of circular extrachromosomal DNA in the nuclear genome of Trypanosoma brucei
    N S Alsford
    School of Biological Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK
    Mol Microbiol 47:277-89. 2003
    ..Therefore, we discuss a functional connection between the occurrence of this circular DNA and subtelomeric recombination events in T. brucei...
  19. 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
    ....
  20. 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
  21. 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...
  22. 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...
  23. 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...
  24. 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
  25. doi request reprint Receptor-mediated endocytosis for drug delivery in African trypanosomes: fulfilling Paul Ehrlich's vision of chemotherapy
    Sam Alsford
    Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Trends Parasitol 29:207-12. 2013
    ..Here, we argue that receptor-mediated endocytosis represents both a validated drug target and a promising route for the delivery of novel therapeutics into trypanosomes...