Genomes and Genes
Affiliation: London School of Hygien & Tropical Medicine
Location: London, UK
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.
Characterisation of uptake and sub-cellular transit of human serum trypanolytic factors by Trypanosoma brucei, 2013, MRC
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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...
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- Alsford S, Horn D. RNA polymerase I transcription stimulates homologous recombination in Trypanosoma brucei. Mol Biochem Parasitol. 2007;153:77-9 pubmed
- 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
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..