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. Alsford S, Kawahara T, Glover L, Horn D. Tagging a T. brucei RRNA locus improves stable transfection efficiency and circumvents inducible expression position effects. Mol Biochem Parasitol. 2005;144:142-8 pubmed
    ..The developments described should facilitate functional analysis and increased throughput. ..
  2. Baker N, Alsford S, Horn D. Genome-wide RNAi screens in African trypanosomes identify the nifurtimox activator NTR and the eflornithine transporter AAT6. Mol Biochem Parasitol. 2011;176:55-7 pubmed publisher
    ..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. Alsford S, Kemp L, Kawahara T, Horn D. RNA interference, growth and differentiation appear normal in African trypanosomes lacking Tudor staphylococcal nuclease. Mol Biochem Parasitol. 2010;174:70-3 pubmed publisher
    ..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. ..
  4. Field M, Horn D, Alsford S, Koreny L, Rout M. Telomeres, tethers and trypanosomes. Nucleus. 2012;3:478-86 pubmed publisher
    ..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. ..
  5. Alsford S, Glover L, Horn D. Multiplex analysis of RNA interference defects in Trypanosoma brucei. Mol Biochem Parasitol. 2005;139:129-32 pubmed
  6. Alsford S, Horn D. Trypanosomatid histones. Mol Microbiol. 2004;53:365-72 pubmed
  7. Camacho M, Alsford S, Agnew A. Molecular forms of tegumental and muscle acetylcholinesterases of Schistosoma. Parasitology. 1996;112 ( Pt 2):199-204 pubmed
    ..A substantial amount of this enzyme is phosphatidylinositol (PI) anchored since it could be released by PI-specific phospholipase C from both muscle and tegumental membranes. ..
  8. Alsford S, Kelly J, Baker N, Horn D. Genetic dissection of drug resistance in trypanosomes. Parasitology. 2013;140:1478-91 pubmed publisher
    ..The new knowledge gained should inform the development of novel interventions against the devastating diseases caused by these parasites. ..
  9. Glover L, Alsford S, Horn D. DNA break site at fragile subtelomeres determines probability and mechanism of antigenic variation in African trypanosomes. PLoS Pathog. 2013;9:e1003260 pubmed publisher
    ..Our results show how subtelomere fragility can generate the triggers for the major antigenic variation mechanisms in the African trypanosome...

More Information

Publications28

  1. Alsford S, Kawahara T, Isamah C, Horn D. A sirtuin in the African trypanosome is involved in both DNA repair and telomeric gene silencing but is not required for antigenic variation. Mol Microbiol. 2007;63:724-36 pubmed
    ..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. ..
  2. Gull K, Alsford S, Ersfeld K. Segregation of minichromosomes in trypanosomes: implications for mitotic mechanisms. Trends Microbiol. 1998;6:319-23 pubmed
    ..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. ..
  3. Alsford S, Eckert S, Baker N, Glover L, Sanchez Flores A, Leung K, et al. High-throughput decoding of antitrypanosomal drug efficacy and resistance. Nature. 2012;482:232-6 pubmed publisher
  4. Alsford S, Horn D, Glover L. DNA breaks as triggers for antigenic variation in African trypanosomes. Genome Biol. 2009;10:223 pubmed publisher
    ..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. ..
  5. Alsford S, Horn D. Cell-cycle-regulated control of VSG expression site silencing by histones and histone chaperones ASF1A and CAF-1b in Trypanosoma brucei. Nucleic Acids Res. 2012;40:10150-60 pubmed publisher
    ..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. ..
  6. DuBois K, Alsford S, Holden J, Buisson J, Swiderski M, Bart J, et al. NUP-1 Is a large coiled-coil nucleoskeletal protein in trypanosomes with lamin-like functions. PLoS Biol. 2012;10:e1001287 pubmed publisher
    ..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. Alsford S, Horn D. Elongator protein 3b negatively regulates ribosomal DNA transcription in african trypanosomes. Mol Cell Biol. 2011;31:1822-32 pubmed publisher
    ..ELP3b is also the first trypanosome protein shown to distinguish between rDNA and variant surface glycoprotein transcription within different RNAP-I compartments. ..
  8. Alsford S, Field M, Horn D. Receptor-mediated endocytosis for drug delivery in African trypanosomes: fulfilling Paul Ehrlich's vision of chemotherapy. Trends Parasitol. 2013;29:207-12 pubmed publisher
    ..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. ..
  9. Camacho M, Alsford S, Jones A, Agnew A. Nicotinic acetylcholine receptors on the surface of the blood fluke Schistosoma. Mol Biochem Parasitol. 1995;71:127-34 pubmed
    ..Both AChE and nAChR were concentrated on the dorsal surface of the adult male. These results indicate a role for AChE and AChR associated with the transporting function of this membrane. ..
  10. Alsford S, Horn D. Single-locus targeting constructs for reliable regulated RNAi and transgene expression in Trypanosoma brucei. Mol Biochem Parasitol. 2008;161:76-9 pubmed publisher
    ..The constructs are integrated at a single, marked locus and deliver reliable and reproducible expression. ..
  11. Alsford S, Horn D. RNA polymerase I transcription stimulates homologous recombination in Trypanosoma brucei. Mol Biochem Parasitol. 2007;153:77-9 pubmed
  12. Ersfeld K, Docherty R, Alsford S, Gull K. A fluorescence in situ hybridisation study of the regulation of histone mRNA levels during the cell cycle of Trypanosoma brucei. Mol Biochem Parasitol. 1996;81:201-9 pubmed
  13. Alsford S, Turner D, Obado S, Sanchez Flores A, Glover L, Berriman M, et al. High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome. Genome Res. 2011;21:915-24 pubmed publisher
    ..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. ..
  14. Kawahara T, Siegel T, Ingram A, Alsford S, Cross G, Horn D. Two essential MYST-family proteins display distinct roles in histone H4K10 acetylation and telomeric silencing in trypanosomes. Mol Microbiol. 2008;69:1054-68 pubmed publisher
    ..The results are also consistent with the idea that HAT1 contributes to establishing boundaries between transcriptionally active and repressed telomeric domains in T. brucei. ..
  15. Alsford N, Navarro M, Jamnadass H, Dunbar H, Ackroyd M, Murphy N, et al. The identification of circular extrachromosomal DNA in the nuclear genome of Trypanosoma brucei. Mol Microbiol. 2003;47:277-89 pubmed
    ..Therefore, we discuss a functional connection between the occurrence of this circular DNA and subtelomeric recombination events in T. brucei. ..
  16. Alsford S, Wickstead B, Ersfeld K, Gull K. Diversity and dynamics of the minichromosomal karyotype in Trypanosoma brucei. Mol Biochem Parasitol. 2001;113:79-88 pubmed
    ..This steady telomeric growth, counteracted by stochastic large losses of telomeric sequences is the most likely cause of minichromosome karyotype heterogeneity within a population. ..
  17. Alsford S, Dubois K, Horn D, Field M. Epigenetic mechanisms, nuclear architecture and the control of gene expression in trypanosomes. Expert Rev Mol Med. 2012;14:e13 pubmed publisher
    ..Therefore, both evolutionarily common and novel mechanisms cohabit in trypanosomes, offering both important biological insights and possible therapeutic opportunity. ..
  18. Glover L, Alsford S, Beattie C, Horn D. Deletion of a trypanosome telomere leads to loss of silencing and progressive loss of terminal DNA in the absence of cell cycle arrest. Nucleic Acids Res. 2007;35:872-80 pubmed
    ..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. ..
  19. Macedo J, Currier R, Wirdnam C, Horn D, Alsford S, Rentsch D. Ornithine uptake and the modulation of drug sensitivity in Trypanosoma brucei. FASEB J. 2017;31:4649-4660 pubmed publisher
    ..Macedo, J. P., Currier, R. B., Wirdnam, C., Horn, D., Alsford, S., Rentsch, D. Ornithine uptake and the modulation of drug sensitivity in Trypanosoma brucei. ..