Publications by authors named "Collette Britton"

Sulphite oxidase has an essential role in detoxifying environmental and endogenously generated sulphite into sulphate and requires the molybdenum cofactor (Moco) to function. Until recently it was believed that the synthesis pathway for Moco was so important for survival that it was conserved in all multicellular animals. Here we report the use of comparative genomics to identify the absence of the first enzyme involved in Moco synthesis in Haemonchus contortus, a highly pathogenic and economically important helminth of livestock that, similar to many parasitic nematode species, has proved difficult to maintain in vitro.

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Upon parasitic helminth infection, activated intestinal tuft cells secrete interleukin-25 (IL-25), which initiates a type 2 immune response during which lamina propria type 2 innate lymphoid cells (ILC2s) produce IL-13. This causes epithelial remodeling, including tuft cell hyperplasia, the function of which is unknown. We identified a cholinergic effector function of tuft cells, which are the only epithelial cells that expressed choline acetyltransferase (ChAT).

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Background: Strongyloides stercoralis is a soil-transmitted intestinal nematode with a complex life cycle that primarily affects humans, non-human primates, dogs, and occasionally cats. This study presents, to the best of our knowledge, the first case of S. stercoralis infection and its genotyping in a domestic dog from Argentina.

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Tuft cells have recently emerged as the focus of intense interest following the discovery of their chemosensory role in the intestinal tract, and their ability to activate Type 2 immune responses to helminth parasites. Moreover, they populate a wide range of mucosal tissues and are intimately connected to immune and neuronal cells, either directly or through the release of pharmacologically active mediators. They are now recognised to fulfil both homeostatic roles, in metabolism and tissue integrity, as well as acting as the first sensors of parasite infection, immunity to which is lost in their absence.

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Santa Ines (SI) and Ile de France (IF) sheep are known to be resistant and susceptible to Haemonchus contortus infection, respectively. Several studies have shown some genes as potential biological markers for sheep resistance against gastrointestinal nematodes using molecular tools, including transcriptomic analysis. In this study, we sequenced the polyadenylated RNA of the abomasal tissue of SI and IF suckling lambs to identify mucosa-specific transcript alterations between breeds artificially infected with H.

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Article Synopsis
  • Understanding how parasites survive and affect host immune responses is key for improving disease management and developing new treatments.
  • Traditional methods like microarray and RNA sequencing give insights into gene expression during parasite development but miss details about different cell types and their organization.
  • Single-cell RNA sequencing (scRNA-seq) provides a deeper look at gene expression in individual cells and can be complemented by using organoids to study host-parasite interactions and parasite growth in a lab setting.
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  • Parasitic helminths, like other pathogens, can quickly develop resistance to drugs, making it crucial to understand the genetics behind this resistance, especially in nematodes.
  • This study used genetic crosses in natural hosts to map resistance genes for major classes of anthelmintics, identifying new alleles linked to resistance against benzimidazoles, levamisole, and ivermectin.
  • The findings pinpoint the gene cky-1 as significant for ivermectin survival, providing a pathway for developing molecular diagnostics to address drug resistance in parasitic infections.
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  • Ivermectin is crucial for global health in humans and animals, but resistance to the drug is widespread in parasites, raising concerns about treatment effectiveness.
  • Despite extensive research, the genetic basis for this resistance in parasitic helminths remains poorly understood due to their complex genomes and evolutionary factors.
  • A genetic study of Haemonchus contortus revealed that resistant populations exhibit specific gene expression changes linked to ivermectin resistance, including upregulation of key genes involved in neuronal function and cellular processes.
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Santa Ines, an indigenous Brazilian hair sheep, in comparison with European sheep breeds (e.g., Ile de France), show greater resistance against gastrointestinal nematode (GIN) infections, mainly to Haemonchus contortus.

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Article Synopsis
  • * Research on tuft cells, a specific type of epithelial cell in mice that reacts to helminth infections, reveals their presence and function in sheep, particularly in the abomasum during nematode infections.
  • * The study identifies differences in receptor expression between ovine and murine tuft cells, suggesting a unique immune response in ruminants that could inform future vaccine development against parasitic nematodes.
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Haemonchus contortus is a globally distributed and economically important gastrointestinal pathogen of small ruminants and has become a key nematode model for studying anthelmintic resistance and other parasite-specific traits among a wider group of parasites including major human pathogens. Here, we report using PacBio long-read and OpGen and 10X Genomics long-molecule methods to generate a highly contiguous 283.4 Mbp chromosome-scale genome assembly including a resolved sex chromosome for the MHco3(ISE).

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This review addresses the research landscape regarding vaccines against scour worms, particularly Trichostrongylus spp. and Teladorsagia circumcincta. The inability of past research to deliver scour-worm vaccines with reliable and reproducible efficacy has been due in part to gaps in knowledge concerning: (i) host-parasite interactions leading to development of type-2 immunity, (ii) definition of an optimal suite of parasite antigens, and (iii) rational formulation and administration to induce protective immunity against gastrointestinal nematodes (GIN) at the site of infestation.

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Article Synopsis
  • * Researchers demonstrated that cell-free genomic DNA (cfDNA) can be extracted from archived plasma and serum samples, enabling genetic studies on samples stored for up to 35 years.
  • * Using this cfDNA method, the study examined the MHC class II DRB1 locus in 224 Merino sheep, revealing 51 different DRB1 alleles and offering a new way to analyze genetic diversity related to vaccination and infection in various species.
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Article Synopsis
  • Small RNAs, such as microRNAs (miRNAs), Piwi-interacting RNAs (piRNAs), and small interfering RNAs (siRNAs), are key regulators of gene expression and are found in various organisms, including parasitic nematodes.
  • Research using genome data and small RNA sequencing has revealed the expression patterns of these small RNAs during different lifecycle stages of nematodes and their potential roles in regulating gene expression in both the parasites and their hosts.
  • The review highlights how miRNAs influence development in nematodes and suggests that piRNAs and siRNAs help suppress certain genes, with advancements in RNA interference continuing to enhance our understanding of these small RNAs' functions.
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  • The study focuses on understanding how different sheep breeds respond immunologically to infections caused by the Haemonchus contortus parasite, which is crucial for developing better parasite control methods like vaccines and genetic selection.
  • It compares the immune response of the resistant Santa Ines breed and the susceptible Ile de France breed, showing that Santa Ines lambs had lower parasite loads, higher eosinophils, and quicker antibody responses.
  • Additionally, the Santa Ines showed stronger immune responses in the abomasum, including higher levels of specific immune cells and antibodies, indicating a greater ability to defend against gastrointestinal nematodes, which could inform resistance breeding strategies.
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  • Parasitic nematodes, like Haemonchus contortus, shift between free-living and parasitic stages, and understanding how this transition is controlled is still not fully understood.
  • This study identified two specific microRNAs (mir-228 and mir-235) that are crucial during the infective larval stage and may help maintain the nematodes in an arrested development state.
  • The research suggests that these miRNAs interact with insulin signaling pathways to regulate growth and could be targeted for potential therapies to manage parasitic infections.
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Anthelmintic resistance is a threat to global food security. In order to alleviate the selection pressure for resistance and maintain drug efficacy, management strategies increasingly aim to preserve a proportion of the parasite population in 'refugia', unexposed to treatment. While persuasive in its logic, and widely advocated as best practice, evidence for the ability of refugia-based approaches to slow the development of drug resistance in parasitic helminths is currently limited.

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Some nematode species are economically important parasites of livestock, while others are important human pathogens causing some of the most important neglected tropical diseases. In both humans and animals, anthelmintic drug administration is the main control strategy, but the emergence of drug-resistant worms has stimulated the development of alternative control approaches. Among these, vaccination is considered to be a sustainable and cost effective strategy.

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Article Synopsis
  • The nematode Haemonchus contortus significantly impacts small ruminant health and agriculture due to its resistance to anthelmintic drugs, posing challenges for livestock sustainability worldwide.
  • Researchers conducted a genetic cross between two strains to create a chromosome-scale genetic map, revealing insights into the genome's variation, recombination rates, and polyandry affecting progeny genetics.
  • The study advances our understanding of parasitic helminth genetics and resistance, emphasizing the potential of whole-genome resequencing for mapping genetic traits in non-model organisms.
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Tackling Hypotheticals in Helminth Genomes.

Trends Parasitol

March 2018

Advancements in genome sequencing have led to the rapid accumulation of uncharacterized 'hypothetical proteins' in the public databases. Here we provide a community perspective and some best-practice approaches for the accurate functional annotation of uncharacterized genomic sequences.

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Resistance to anthelmintic drugs is a major problem in the global fight against parasitic nematodes infecting humans and animals. While previous studies have identified mutations in drug target genes in resistant parasites, changes in the expression levels of both targets and transporters have also been reported. The mechanisms underlying these changes in gene expression are unresolved.

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Article Synopsis
  • * The cluster of miRNAs can be detected in sheep infected with H. contortus, suggesting their release into host tissues, and the worms secrete extracellular vesicles containing these miRNAs.
  • * Analysis of the small RNA content shows that while some miRNAs are found in vesicles, others are more prevalent in a non-vesicular form, with insights pointing to the gut as the source of miRNAs in L4 stage larvae, highlighting
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Over the last decade microRNAs (miRNAs) and small interfering RNAs (siRNAs) have emerged as important regulators of post-transcriptional gene expression. miRNAs are short, non-coding RNAs that regulate a variety of processes including cancer, organ development and immune function. This class of small RNAs bind with partial complementarity to their target mRNA sequences, most often in the 3'UTR, to negatively regulate gene expression.

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Background: Filarial nematodes are important pathogens in the tropics transmitted to humans via the bite of blood sucking arthropod vectors. The molecular mechanisms underpinning survival and differentiation of these parasites following transmission are poorly understood. microRNAs are small non-coding RNA molecules that regulate target mRNAs and we set out to investigate whether they play a role in the infection event.

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microRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation. They were first identified in the free-living nematode Caenorhabditis elegans, where the miRNAs lin-4 and let-7 were shown to be essential for regulating correct developmental progression. The sequence of let-7 was subsequently found to be conserved in higher organisms and changes in expression of let-7, as well as other miRNAs, are associated with certain cancers, indicating important regulatory roles.

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