- Parasite Biology and Host Interactions
- Parasites and Host Interactions
- Chromosomal and Genetic Variations
- Genomics and Phylogenetic Studies
- Research on Leishmaniasis Studies
- Metallurgy and Material Science
- Trace Elements in Health
- Parasitic Diseases Research and Treatment
- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- HIV-related health complications and treatments
- Eosinophilic Esophagitis
- SARS-CoV-2 detection and testing
- Viral gastroenteritis research and epidemiology
- Genetics, Aging, and Longevity in Model Organisms
- Genomics and Chromatin Dynamics
- Helminth infection and control
- Insect symbiosis and bacterial influences
- SARS-CoV-2 and COVID-19 Research
- IL-33, ST2, and ILC Pathways
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Viral Infections and Vectors
- RNA Research and Splicing
- Parasitic infections in humans and animals
University of Cambridge
2008-2025
Lawn Tennis Association
2022
Wellcome Sanger Institute
2011-2021
The Gurdon Institute
2019
Genomics (United Kingdom)
2019
Centro de Excelência em Bioinformática
2012
Shanghai Jiao Tong University
2012
University of Georgia
2012
Universidad de la República
2008
Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of 363 megabase nuclear genome blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families micro-exon genes undergo frequent alternative splicing. As first sequenced flatworm, a representative Lophotrochozoa, it offers insights into early events evolution animals, including development...
Schistosomiasis is one of the most prevalent parasitic diseases, affecting millions people in developing countries. Amongst human-infective species, Schistosoma mansoni also commonly used laboratory and here we present systematic improvement its draft genome. We Sanger capillary deep-coverage Illumina sequencing from clonal worms to upgrade highly fragmented 380 Mb genome with only 885 scaffolds more than 81% bases organised into chromosomes. have transcriptome (RNA-seq) four time points...
In the study of transposable elements (TEs), generation a high confidence set consensus sequences that represent diversity TEs found in given genome is key step path to investigate these fascinating genomic elements. Many algorithms and pipelines are available automatically identify putative TE families present genome. Despite availability valuable resources, producing library high-quality full-length largely remains process manual curation. This know-how often passed on from...
Abstract The HUSH complex represses retroviruses, transposons and genes to maintain the integrity of vertebrate genomes. regulates deposition epigenetic mark H3K9me3, but how its three core subunits — TASOR, MPP8 Periphilin contribute assembly targeting remains unknown. Here, we define biochemical basis find that modular architecture resembles yeast RNA-induced transcriptional silencing complex. central subunit, associates with RNA processing components. TASOR is required for H3K9me3 over...
Platyhelminth parasites are a major health problem in developing countries. In contrast to their mammalian hosts, platyhelminth thiol-disulfide redox homeostasis relies on linked thioredoxin-glutathione systems, which fully dependent reductase (TGR), promising drug target. TGR is homodimeric enzyme comprising glutaredoxin domain and thioredoxin (TR) domains with C-terminal center containing selenocysteine (Sec). this study, we demonstrate the existence of functional systems cytosolic...
Efforts to define serological correlates of protection against COVID-19 have been hampered by the lack a simple, scalable, standardised assay for SARS-CoV-2 infection and antibody neutralisation. Plaque assays remain gold standard, but are impractical high-throughput screening. In this study, we show that expression viral proteases may be used quantitate infected cells. Our exploit cleavage specific oligopeptide linkers, leading activation cell-based optical biosensors. First, characterise...
The transcription factor Rora has been shown to be important for the development of ILC2 and regulation ILC3, macrophages Treg cells. Here we investigate role across CD4+ T cells in general, but with an emphasis on Th2 cells, both vitro as well context several vivo type 2 infection models. We dissect function using overexpression a CD4-conditional Rora-knockout mouse, RORA-reporter mouse. establish importance controlling lung inflammation induced by Nippostrongylus brasiliensis infection,...
Schistosome infection begins with the penetration of cercariae through healthy unbroken host skin. This process leads to transformation free-living larvae into obligate parasites called schistosomula. irreversible transformation, which occurs in as little two hours, involves casting cercaria tail and complete remodelling surface membrane. At this stage, are vulnerable immune attack oxidative stress. Consequently, mechanisms by parasite recognises swiftly adapts human still subject many...
ABSTRACT People in regions of Schistosoma mansoni endemicity slowly acquire immunity, but why this takes years to develop is still not clear. It has been associated with increases parasite-specific IgE, induced, some investigators propose, antigens exposed during the death adult worms. These include members tegumental-allergen-like protein family (TAL1 TAL13). Previously, a group S. -infected Ugandan males, we showed that IgE responses three TALs expressed worms (TAL1, -3, and -5) became...
Schistosomes are parasitic blood flukes that survive for many years within the mammalian host vasculature. How parasites establish a chronic infection in hostile bloodstream environment, whilst evading immune response is poorly understood. The parasite develops morphologically and grows as it migrates to its preferred vascular niche, avoiding or repairing damage from system. In this study, we investigated temporal changes gene expression during intra-mammalian development of Schistosoma...
The new release of SchistoDB (http://SchistoDB.net) provides a rich resource genomic data for key blood flukes (genus Schistosoma) which cause disease in hundreds millions people worldwide. integrates whole-genome sequence and annotation three species the genus enhanced bioinformatics analyses data-mining tools. A simple, yet comprehensive web interface provided through Strategies Web Development Kit is available mining visualization data. Genomic scale can be queried based on BLAST...
Schistosomes are parasitic helminths that cause schistosomiasis, a disease affecting circa 200 million people, primarily in underprivileged regions of the world. Schistosoma mansoni is most experimentally tractable schistosome species due to its ease propagation laboratory and high quality genome assembly annotation. Although there growing interest microRNAs (miRNAs) trematodes, little known about role these molecules play context developmental processes. We use completely unaware...
Abstract Background The thioredoxin and/or glutathione pathways occur in all organisms. They provide electrons for deoxyribonucleotide synthesis, function as antioxidant defenses, detoxification, Fe/S biogenesis and participate a variety of cellular processes. In contrast to their mammalian hosts, platyhelminth (flatworm) parasites studied so far, lack conventional systems. Instead, they possess linked thioredoxin-glutathione system with the selenocysteine-containing enzyme reductase (TGR)...
Background Blood flukes (Schistosoma spp.) are parasites that can survive for years or decades in the vasculature of permissive mammalian hosts, including humans. Proteolytic enzymes (proteases) crucial successful parasitism, aspects invasion, maturation and reproduction. Most attention has focused on 'cercarial elastase' serine proteases facilitate skin invasion by infective schistosome larvae, cysteine aspartic worms use to digest blood meal. Apart from cercarial elastases, information...
Schistosomiasis is a significant public health problem in sub-Saharan Africa, China, South-East Asia and regions of South central America affecting about 189 million people. Kunitz-type serine protease inhibitors have been identified as important players the interaction other flatworm parasites with their mammalian hosts. Here, we evaluate protective efficacy chemically synthesized T- B-cell peptide epitopes derived from kunitz protein Schistosoma mansoni. Putative kunitz-type inhibitor...
Filarial nematodes are important pathogens in the tropics transmitted to humans via bite of blood sucking arthropod vectors. The molecular mechanisms underpinning survival and differentiation these parasites following transmission poorly understood. microRNAs small non-coding RNA molecules that regulate target mRNAs we set out investigate whether they play a role infection event. differentially expressed during early post-infective stages Brugia pahangi L3 were identified by microarray...
The seminal description of the cellular restriction factor APOBEC3G and its antagonism by HIV-1 Vif has underpinned two decades research on host-virus interaction. We recently reported that is also able to degrade PPP2R5 family regulatory subunits key phosphatase PP2A (PPP2R5A-E; Greenwood et al., 2016; Naamati 2019). now identify amino acid polymorphisms at positions 31 128 which selectively regulate degradation proteins. These residues covary across viruses in vivo, favouring depletion...
Schistosomiasis is the most important helminthic disease of humanity in terms morbidity and mortality. Facile manipulation schistosomes using lentiviruses would enable advances functional genomics these related neglected tropical diseases pathogens including tapeworms, their non-dividing cells. Such approaches have hitherto been unavailable. Blood stream forms human blood fluke, Schistosoma mansoni, causative agent hepatointestinal schistosomiasis, were infected with HIV-1 isolate NL4-3...
Endogenous viral elements (EVEs), accounting for 15% of our genome, serve as a genetic reservoir from which new genes can emerge. Nematode EVEs are particularly diverse and informative virus evolution. We identify Atlas virus-an intact retrovirus-like EVE in the human hookworm
Abstract Platyhelminthes, also known as flatworms, is a phylum of bilaterian invertebrates infamous for their parasitic representatives. The classes Cestoda, Monogenea, and Trematoda comprise helminths inhabiting multiple hosts, including fishes, humans, livestock, are responsible considerable economic damage burden on human health. As in other animals, the genomes flatworms have wide variety paralogs, genes related via duplication, whose origins could be mapped throughout evolution phylum....
The genomes of numerous parasitic nematodes are currently being sequenced, but their complexity and size, together with high levels intra-specific sequence variation a lack reference genomes, makes assembly annotation challenging task. Haemonchus contortus is an economically significant parasite livestock that widely used for basic research as well vaccine development drug discovery. It one many medically important parasites within the strongylid nematode group. This group has closest...
Background The use of DNA microarray technology to study global Schistosoma gene expression has led the rapid identification novel biological processes, pathways or associations. Implementation standardized protocols across laboratories would assist maximal interpretation generated datasets and extend productive application this technology. Methodology/Principal Findings Utilizing a new mansoni oligonucleotide composed 37,632 elements, we show that schistosome genomic (gDNA) hybridizes with...
Schistosomiasis is a major global health problem caused by blood-dwelling parasitic worms, which currently tackled primarily mass administration of the drug praziquantel. Appropriate treatment strategies are informed diagnostics that establish prevalence and intensity infection, which, in regions low transmission, should be highly sensitive.To identify sensitive new serological markers Schistosoma mansoni infections, we have compiled recombinant protein library parasite cell-surface secreted...