Veterinary Biosciences - Research Publications

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    Elucidating the molecular and developmental biology of parasitic nematodes: Moving to a multiomics paradigm
    Ma, G ; Wang, T ; Korhonen, PK ; Hofmann, A ; Sternberg, PW ; Young, ND ; Gasser, RB ; Rollinson, D ; Stothard, R (ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD, 2020-01-01)
    In the past two decades, significant progress has been made in the sequencing, assembly, annotation and analyses of genomes and transcriptomes of parasitic worms of socioeconomic importance. This progress has somewhat improved our knowledge and understanding of these pathogens at the molecular level. However, compared with the free-living nematode Caenorhabditis elegans, the areas of functional genomics, transcriptomics, proteomics and metabolomics of parasitic nematodes are still in their infancy, and there are major gaps in our knowledge and understanding of the molecular biology of parasitic nematodes. The information on signalling molecules, molecular pathways and microRNAs (miRNAs) that are known to be involved in developmental processes in C. elegans and the availability of some molecular resources (draft genomes, transcriptomes and some proteomes) for selected parasitic nematodes provide a basis to start exploring the developmental biology of parasitic nematodes. Indeed, some studies have identified molecules and pathways that might associate with developmental processes in related, parasitic nematodes, such as Haemonchus contortus (barber's pole worm). However, detailed information is often scant and ‘omics resources are limited, preventing a proper integration of ‘omic data sets and comprehensive analyses. Moreover, little is known about the functional roles of pheromones, hormones, signalling pathways and post-transcriptional/post-translational regulations in the development of key parasitic nematodes throughout their entire life cycles. Although C. elegans is an excellent model to assist molecular studies of parasitic nematodes, its use is limited when it comes to explorations of processes that are specific to parasitism within host animals. A deep understanding of parasitic nematodes, such as H. contortus, requires substantially enhanced resources and the use of integrative ‘omics approaches for analyses. The improved genome and well-established in vitro larval culture system for H. contortus provide unprecedented opportunities for comprehensive studies of the transcriptomes (mRNA and miRNA), proteomes (somatic, excretory/secretory and phosphorylated proteins) and lipidomes (e.g., polar and neutral lipids) of this nematode. Such resources should enable in-depth explorations of its developmental biology at a level, not previously possible. The main aims of this review are (i) to provide a background on the development of nematodes, with a particular emphasis on the molecular aspects involved in the dauer formation and exit in C. elegans; (ii) to critically appraise the current state of knowledge of the developmental biology of parasitic nematodes and identify key knowledge gaps; (iii) to cover salient aspects of H. contortus, with a focus on the recent advances in genomics, transcriptomics, proteomics and lipidomics as well as in vitro culturing systems; (iv) to review recent advances in our knowledge and understanding of the molecular and developmental biology of H. contortus using an integrative multiomics approach, and discuss the implications of this approach for detailed explorations of signalling molecules, molecular processes and pathways likely associated with nematode development, adaptation and parasitism, and for the identification of novel intervention targets against these pathogens. Clearly, the multiomics approach established recently is readily applicable to exploring a wide range of interesting and socioeconomically significant parasitic worms (including also trematodes and cestodes) at the molecular level, and to elucidate host–parasite interactions and disease processes.
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    Understanding Haemonchus contortus Better Through Genomics and Transcriptomics
    Gasser, RB ; Schwarz, EM ; Korhonen, PK ; Young, ND ; Gasser, RB ; VonSamsonHimmelstjerna, G (ELSEVIER ACADEMIC PRESS INC, 2016)
    Parasitic roundworms (nematodes) cause substantial mortality and morbidity in animals globally. The barber's pole worm, Haemonchus contortus, is one of the most economically significant parasitic nematodes of small ruminants worldwide. Although this and related nematodes can be controlled relatively well using anthelmintics, resistance against most drugs in common use has become a major problem. Until recently, almost nothing was known about the molecular biology of H. contortus on a global scale. This chapter gives a brief background on H. contortus and haemonchosis, immune responses, vaccine research, chemotherapeutics and current problems associated with drug resistance. It also describes progress in transcriptomics before the availability of H. contortus genomes and the challenges associated with such work. It then reviews major progress on the two draft genomes and developmental transcriptomes of H. contortus, and summarizes their implications for the molecular biology of this worm in both the free-living and the parasitic stages of its life cycle. The chapter concludes by considering how genomics and transcriptomics can accelerate research on Haemonchus and related parasites, and can enable the development of new interventions against haemonchosis.
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    Harnessing the Toxocara Genome to Underpin Toxocariasis Research and New Interventions
    Gasser, RB ; Korhonen, PK ; Zhux, X-Q ; Young, ND ; Rollinson, D ; Stothard, JR (ELSEVIER ACADEMIC PRESS INC, 2016)
    Parasitic worms, such as flatworms (platyhelminths) and roundworms (nematodes), cause substantial morbidity and mortality in animals and people globally. The ascaridoid nematode Toxocara canis is a zoonotic parasite of socioeconomic significance worldwide. In humans, this worm causes toxocariasis (disease) mainly in underprivileged communities in both the developed and developing worlds. While reasonably well studied from clinical and epidemiological perspectives, little is understood about the molecular biology of T. canis, its relationship with its hosts and the disease that it causes. However, a recent report of the draft genome and transcriptomes of T. canis should underpin many fundamental and applied research areas in the future. The present article gives a background on Toxocara and toxocariasis, a brief account of diagnostic approaches for specific identification and genetic analysis, and gives a perspective on the impact that the genome of T. canis and advanced molecular technologies could have on our understanding of the parasite and the diseases that it causes as well as the design of new and improved approaches for the diagnosis, treatment and control of toxocariasis.