A5006899799- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Insect symbiosis and bacterial influences
- Biochemical and Molecular Research
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Lysosomal Storage Disorders Research
- Signaling Pathways in Disease
- Music History and Culture
- Parasites and Host Interactions
- Chromosomal and Genetic Variations
- Plant Virus Research Studies
- RNA Research and Splicing
- Synthesis and Biological Evaluation
- Musicology and Musical Analysis
- Cardiomyopathy and Myosin Studies
- RNA modifications and cancer
- Genomics and Phylogenetic Studies
- Cytomegalovirus and herpesvirus research
- Calcium signaling and nucleotide metabolism
- Histone Deacetylase Inhibitors Research
- Mosquito-borne diseases and control
- HIV/AIDS drug development and treatment
- Race, History, and American Society
- Folklore, Mythology, and Literature Studies
University of Dundee
2015-2024
Wellcome Centre for Anti-Infectives Research
2017-2024
Wellcome Trust
2016-2022
Tel Aviv University
2010-2021
University of Geneva
2018
ORCID
2018
SKA Telescope, South Africa
2018
University of Notre Dame
2016
Western University of Health Sciences
2015
Drug Discovery Laboratory (Norway)
2015
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...
Leishmania species cause a spectrum of human diseases in tropical and subtropical regions the world. We have sequenced 36 chromosomes 32.8-megabase haploid genome major (Friedlin strain) predict 911 RNA genes, 39 pseudogenes, 8272 protein-coding which 36% can be ascribed putative function. These include genes involved host-pathogen interactions, such as proteolytic enzymes, extensive machinery for synthesis complex surface glycoconjugates. The organization into long, strand-specific,...
African trypanosomes are major pathogens of humans and livestock represent a model for studies unusual protozoal biology. We describe high-throughput phenotyping approach termed RNA interference (RNAi) target sequencing, or RIT-seq that, using Illumina maps fitness-costs associated with RNAi. scored the abundance >90,000 integrated RNAi targets recovered from trypanosome libraries before after induction Data presented 7435 protein coding sequences, >99% non-redundant set in Trypanosoma...
Nifurtimox and benznidazole are the front-line drugs used to treat Chagas disease, most important parasitic infection in Americas. These agents function as prodrugs must be activated within parasite have trypanocidal effects. Despite >40 years of research, mechanism(s) action resistance remained elusive. Here, we report that trypanosomes, both by a NADH-dependent, mitochondrially localized, bacterial-like, type I nitroreductase (NTR), down-regulation this explains how may emerge. Loss...
Visceral leishmaniasis (VL), caused by the protozoan parasites Leishmania donovani and infantum, is one of major parasitic diseases worldwide. There an urgent need for new drugs to treat VL, because current therapies are unfit purpose in a resource-poor setting. Here, we describe development preclinical drug candidate, GSK3494245/DDD01305143/compound 8, with potential this neglected tropical disease. The compound series was discovered repurposing hits from screen against related parasite...
Mechanisms for the degeneration of large-scale interfacial gravity waves are identified lakes in which effects Earth's rotation can be neglected. By assuming a simple two-layer model and comparing timescales over each these mechanisms act, regimes defined particular processes expected to dominate. The boundaries expressed terms two lengthscale ratios: ratio amplitude initial wave depth thermocline, thermocline overall lake. Comparison predictions this timescale analysis with results from...
African trypanosomes cause sleeping sickness in humans, a disease that is typically fatal without chemotherapy. Unfortunately, drug resistance common and melarsoprol-resistant often display cross-resistance to pentamidine. Although melarsoprol/pentamidine (MPXR) has been an area of intense interest for several decades, our understanding the underlying mechanisms remains incomplete. Recently, locus encoding two closely related aquaglyceroporins, AQP2 AQP3, was linked MPXR high-throughput...
A unifying feature of eukaryotic nuclear organization is genome segregation into transcriptionally active euchromatin and repressed heterochromatin. In metazoa, lamin proteins preserve integrity higher order heterochromatin at the periphery, but no non-metazoan orthologues have been identified, despite likely presence nucleoskeletal elements in many lineages. This suggests a metazoan-specific origin for lamins, therefore that distinct protein must compose nucleoskeleton other The...
Trypanosoma brucei drug transporters include the TbAT1/P2 aminopurine transporter and high-affinity pentamidine (HAPT1), but genetic identity of HAPT1 is unknown. We recently reported that loss T. aquaglyceroporin 2 (TbAQP2) caused melarsoprol/pentamidine cross-resistance (MPXR) in these parasites current study aims to delineate mechanism by which this occurs. The TbAQP2 loci isogenic pairs drug-susceptible MPXR strains subspecies were sequenced. Drug susceptibility profiles trypanosome...
African trypanosomes cause lethal and neglected tropical diseases, known as sleeping sickness in humans nagana animals. Current therapies are limited, but fortunately, promising advanced clinical veterinary development, including acoziborole (AN5568 or SCYX-7158) AN11736, respectively. These benzoxaboroles will likely be key to the World Health Organization's target of disease control by 2030. Their mode action was previously unknown. We have developed a high-coverage overexpression library...
Significance Despite intense interest over a period of decades, mechanisms allelic exclusion have remained unsolved mysteries in the field eukaryotic gene expression control. Parasitic African trypanosomes express variant surface glycoproteins (VSGs) monoallelic fashion and long been paradigm for studies this area. We used an RNA interference screen loss identified characterized VSG 1 (VEX1). VEX1 sequestration restricts prevents simultaneous establishment more than one active gene. also...
Protein abundance differs from a few to millions of copies per cell. Trypanosoma brucei presents an excellent model for studies on codon bias and differential gene expression because transcription is broadly unregulated uniform across the genome. T. also major human animal protozoal pathogen. Here, experimental assessment, using synthetic reporter genes, revealed that GC3 codons have positive impact both mRNA protein abundance. Our estimates relative expression, based coding sequences alone...
Abstract The largest gene families in eukaryotes are subject to allelic exclusion, but mechanisms underpinning single allele selection and inheritance remain unclear. Here, we describe a protein complex sustaining variant surface glycoprotein ( VSG ) exclusion antigenic variation Trypanosoma brucei parasites. VSG- exclusion-1 (VEX1) binds both telomeric -associated chromatin VEX2, an ortholog of nonsense-mediated-decay helicase, UPF1. VEX1 VEX2 assemble RNA polymerase-I...