A5043965341- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Biochemical and Molecular Research
- CRISPR and Genetic Engineering
- Plant Virus Research Studies
- DNA Repair Mechanisms
- Insect symbiosis and bacterial influences
- Parasites and Host Interactions
- Chromosomal and Genetic Variations
- Bacterial Genetics and Biotechnology
- Cytomegalovirus and herpesvirus research
- Synthesis and Biological Evaluation
- Parasitic Infections and Diagnostics
- Toxoplasma gondii Research Studies
- Complement system in diseases
- Signaling Pathways in Disease
- RNA and protein synthesis mechanisms
- Calcium signaling and nucleotide metabolism
- DNA and Nucleic Acid Chemistry
- Helminth infection and control
- PARP inhibition in cancer therapy
- Mosquito-borne diseases and control
- Lysosomal Storage Disorders Research
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
Wellcome Centre for Molecular Parasitology
2016-2025
University of Glasgow
2016-2025
Wellcome Trust
2010-2018
Rockefeller University
2016
Universidade Federal de Minas Gerais
2012
University of Guelph
2003-2010
Ontario Institute for Cancer Research
2008-2010
University Health Network
2008-2010
London School of Hygiene & Tropical Medicine
2008
George Washington University
2005
Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that diploid genome contains a predicted 22,570 proteins encoded by genes, which 12,570 represent allelic pairs. Over 50% consists repeated sequences, such as retrotransposons and genes for large families surface molecules, include trans-sialidases, mucins, gp63s, novel family (>1300 copies) mucin-associated protein (MASP) genes. Analyses T. cruzi, brucei , Leishmania major (Tritryp) genomes imply differences...
Identification of replication initiation sites, termed origins, is a crucial step in understanding genome transmission any organism.Transcription the Trypanosoma brucei highly unusual, with each chromosome comprising few discrete transcription units.To understand how DNA occurs context such organization, we have performed genome-wide mapping binding sites initiator ORC1/CDC6 and identified revealing that both localize to boundaries units.A remarkably small number active origins seen, whose...
Abstract Developmental steps in the trypanosome life-cycle involve transition between replicative and non-replicative forms specialised for survival in, transmission between, mammalian tsetse fly hosts. Here, using oligopeptide-induced differentiation vitro, we model progressive development of ‘slender’ to transmissible ‘stumpy’ bloodstream form Trypanosoma brucei capture transcriptomes 8,599 parasites single cell transcriptomics (scRNA-seq). Using this framework, detail relative order...
Aneuploidy is widely observed in both unicellular and multicellular eukaryotes, usually associated with adaptation to stress conditions. Chromosomal duplication stability a tradeoff between the fitness cost of having unbalanced gene copies potential gained from increased dosage specific advantageous genes. Trypanosomatids, family protozoans that include species cause neglected tropical diseases, are relevant group study aneuploidies. Their life cycle has several stressors could select for...
Antigenic variation is an immune evasion strategy used by African trypanosomes, in which the parasites periodically switch expression of VSG genes that encode their protective variant surface glycoprotein coat. Two main routes exist for switching: changing transcriptional status between active and inactive copy site expression, called bloodstream site, or recombination reactions move silent VSGs copies into actively transcribed site. Nothing known about proteins control catalyze these...
Genetic diversity in fungi and mammals is generated through mitotic double-strand break-repair (DSBR), typically involving homologous recombination (HR) or non-homologous end joining (NHEJ). Microhomology-mediated appears to serve a subsidiary function. The African trypanosome, divergent protozoan parasite, relies upon rearrangement of subtelomeric variant surface glycoprotein ( VSG ) genes achieve antigenic variation. Evidence suggests an absence NHEJ but chromosomal repair remains largely...
Poly(ADP-ribosyl)ation by poly(ADP-ribose) polymerases regulates the interaction of many DNA damage and repair factors with sites strand lesions. The these (PAR) is mediated specific domains, including recently identified PAR-binding zinc finger (PBZ) domain. However, mechanism governing interactions unclear. To better understand PBZ-PAR interaction, we performed a detailed examination representative PBZ-containing protein involved in response, aprataxin polynucleotide-kinase-like factor...
Summary Antigenic variation in Trypanosoma brucei has selected for the evolution of a massive archive silent Variant Surface Glycoprotein ( VSG ) genes, which are activated by recombination into specialized expression sites. Such switching can occur at rates substantially higher than background mutation and is dependent on homologous recombination, core DNA repair reaction. A key regulator BRCA2, protein that binds RAD51, enzyme responsible strand exchange. Here, we show T. BRCA2 undergone...
DNA replication initiates on defined genome sites, termed origins. Origin usage appears to follow common rules in the eukaryotic organisms examined date: all chromosomes are replicated from multiple origins, which display variations firing efficiency and selected a larger pool of potential To ask if these features true eukaryotes, we describe genome-wide origin mapping parasite Leishmania. Leishmania suggests striking divergence relative characterized since each chromosome be single origin....
Survival of Trypanosoma brucei depends upon switches in its protective Variant Surface Glycoprotein (VSG) coat by antigenic variation. VSG switching occurs frequent homologous recombination, which is thought to require locus-specific initiation. Here, we show that a RecQ helicase, RECQ2, acts repair DNA breaks, including the telomeric site expression. Despite this, RECQ2 loss does not impair variation, but causes increased arguing against models for switch initiation through direct...