Project description:Anthelmintic resistance is a major problem in the global fight against parasitic nematodes., Most previous studies have focused on the analysis of potential candidate genes that may have a role in resistance. Here we take a novel approach in the important parasite, Haemonchus contortus, by investigating changes in microRNA expression between resistant and susceptible parasites. The resistant worms included two geographically distinct strains and two lines generated by multiple rounds of backcrossing between susceptible and resistant parents, with ivermectin selection. All four resistant strains showed increased abundance of a single miRNA, hco-miR-9551, compared to the susceptible strain. hco-miR-9551 is enriched in female worms, is likely to be located on the X chromosome and is found only in clade V parasitic nematodes. Approximately 5-10% of the genomes of the resistant parental strains are introgressed into the respective backcrosses, suggesting that hco-miR-9551, or genes regulated by the miRNA, may be genetically linked to a locus that determines resistance. Genes containing predicted binding sites for hco-miR-9551 were identified computationally and refined based on differential expression in a transcriptomic dataset. These findings advance our conceptual understanding of the molecular mechanisms of anthelmintic resistance in H. contortus and indicate that altered miRNA expression may be linked with drug resistance.
Project description:Haemonchus contortus is a highly pathogenic parasitic nematode of that can infect a large number of wild and domesticated ruminant species and is the most economically important parasite of sheep and goats worldwide. Although originally a tropical parasite, it has been disseminated around the world by livestock movement and can now be found as far north as the arctic circle. Adult worms are blood feeders that reside in the abomasum (stomach) and are approximately 2cm in length when mature. They are dioecious with single females typically producing several thousand eggs per day which pass out of the host in faeces and develop to infective larvae on the pasture. H. contortus is a member of the superfamily trichostrongyloidea (Strongylida) which contains most of the economically important parasitic nematodes of grazing livestock. These parasites cost the global livestock industry billions of dollars per annum in lost production and drug costs. Resistance to all the major anthelmintic classes is now common worldwide often leading to failure of treatment and control. H. contortus is a close relative of the human hookworm species and belongs to the nearest phylogenetic group of parasites to the free-living model nematode Caenorhabditis elegans . This makes it an important model of parasitic nematode biology that is commonly used for experimental studies. The main objective of this project is to recognize genes expressed in the life stages of H. contortus.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
Project description:Anthelmintic resistance is a major problem in the global fight against parasitic nematodes., Most previous studies have focused on the analysis of potential candidate genes that may have a role in resistance. Here we take a novel approach in the important parasite, Haemonchus contortus, by investigating changes in microRNA expression between resistant and susceptible parasites. The resistant worms included two geographically distinct strains and two lines generated by multiple rounds of backcrossing between susceptible and resistant parents, with ivermectin selection. All four resistant strains showed increased abundance of a single miRNA, hco-miR-9551, compared to the susceptible strain. hco-miR-9551 is enriched in female worms, is likely to be located on the X chromosome and is found only in clade V parasitic nematodes. Approximately 5-10% of the genomes of the resistant parental strains are introgressed into the respective backcrosses, suggesting that hco-miR-9551, or genes regulated by the miRNA, may be genetically linked to a locus that determines resistance. Genes containing predicted binding sites for hco-miR-9551 were identified computationally and refined based on differential expression in a transcriptomic dataset. These findings advance our conceptual understanding of the molecular mechanisms of anthelmintic resistance in H. contortus and indicate that altered miRNA expression may be linked with drug resistance. All samples were carried out using three biological replicates
Project description:Examined expression of microRNAs in different life-cycle stages and gut tissue of the pathogenic nematode Haemonchus contortus and identified differentially expressed miRNAs. Custom array contained probes to 609 Haemonchus contortus miRNA sequence (all mature and start miRNAs identified by Winter et al., 2012, BMC Genomics13:4; DOI: 10.1186/1471-2164-13-4) and all C. elegans sequences in miRBase release 16
Project description:Parasitic nematodes cause diseases that adversely impact on animal health and production. Although advances in genomics and transcriptomics are revolutionising the way we explore these parasites, there is a dearth of proteomic data to underpin or support fundamental discoveries. Here, using a high throughput LC-MS/MS-based approach, we undertook the first large-scale (global) proteomic investigation of Haemonchus contortus (the barber's pole worm), one of the most important parasitic nematodes of livestock animals worldwide. In total, 2487 unique H. contortus proteins, representing five key developmental stages [i. e. eggs, third-stage (L3) and fourth-stage (L4) larvae; female (Af) and male adults (Am)] were identified and quantified with high confidence. Bioinformatic analyses of the somatic proteome of H. contortus discovered substantial alterations in protein profiles during the life cycle, particularly in the transition from the free-living to the parasitic phase, and identified groups of key proteins involved specifically in feeding, digestion, metabolism, development, parasite-host interactions (including immunomodulation), structural remodelling of the body wall and other adaptive processes during the parasitic phase. This global proteomic data set will likely facilitate future molecular, biochemical and physiological investigations of H. contortus and related nematodes, and should underpin the discovery of novel intervention targets against haemonchosis.
2019-03-01 | PXD009956 | Pride
Project description:Drug metabolism
| PRJNA720780 | ENA
Project description:Global studies of arabidopsis developing embryo with overexpressed lipid metabolism genes
Project description:High cholesterol diet and xenobiotic treatment induce changes in cholesterol homeostasis and drug metabolism. Mice were either 7 days on high cholesterol diet or were treated with phenobarbital. Liver samples were analyzed using Sterolgene v0 cDNA microarrays. Sterolgene microarray is a tool designed to enable focused studies of cholesterol homeostasis and drug metabolism. We show that one week of cholesterol diet down-regulates cholesterol biosynthesis and up-regulates xenobiotic metabolism (Cyp3 family). Phenobarbital treatment also up-regulates xenobiotic metabolism (Cyp2b and Cyp3a families). We can conclude that the Sterolgene series of cDNA microarrays represent novel original tool, enabling focused and cost-wise studies of cholesterol homeostasis and drug metabolism. Keywords: Treatment and diet effects