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Conférences

le (9m38s)

Dr Francisco Evangelista - A bioinformatics approach to the discovery of vaccination targets in Ascaris lumbricoides and Ascaris suum.

Background: Ascariasis remains the most prevalent zoonotic helminthic disease affecting both humans and pigs and preventive chemotherapy continues to be the most widespread control method. With recent reports pointing to possible resistance to the commonly used drugs, the development of a vaccine as a complementary control method could be a viable alternative.<br>Methods: Three Ascaris proteomes predicted from whole-genome sequencing data were analysed for potential vaccination targets. Vaccination targets were identified using free and open-access bioinformatic tools (e.g. Vacceed, VaxiJen, Bepipred 2.0) which tested for different characteristics such as sub-cellular location, T-cell and B-cell molecular binding, antigenicity, allergenicity and phylogenetic relationship ...
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le (23m21s)

Dr Peter Geldhof - Natural immunity against Ascaris – What lessons can be learned for vaccine development?

Ascaris lumbricoides and A. suum are large roundworm parasites that thrives in the small intestine of humans and pigs, respectively. The control of ascariasis is currently completely reliant on anthelmintics. However, despite their high efficacy, the long-term benefits of anthelmintics are often disappointing because of rapid reinfections due to a highly contaminated environment. Preventing infection through vaccination would be a great advance and could result in a long-term, efficient control. The search for a vaccine against Ascaris started in the late 1970s and early 1980s with a number of experiments evaluating the protective effects of oral inoculations with UV-radiated eggs. ...
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le (21m27s)

Dr Friederike Ebner - Current challenges of vaccine development against Ascaris

For more than half a century, scientists have been looking for prevention strategies against Ascarids, however, we still lack fully effective vaccines to protect both humans and veterinary species. The hurdles are rather obvious and include the typical parasite problems of tissue migration, immune modulation and immune evasion strategies, antigen diversity and also polymorphisms but most importantly, we only begin to understand how the immune system targets and eliminates the roundworms. These challenges together with rather disappointing results from single antigen vaccines point towards more synergistic approaches. Recent advances in Ascaris ‘omics’ as well as new vaccine platforms will play ...
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Conférences

le (11m52s)

Dr JB Collins - Lack of canonical beta-tubulin resistance alleles in two benzimidazole-resistant ascarid species

Management of nematode parasites of veterinary importance has become complicated because of the development of anthelmintic resistance. Resistance to benzimidazoles (BZ) is the most well characterized and has been linked to mutations in codons 167, 198, or 200 of the isotype-1 beta-tubulin gene in strongylid nematodes. Reports of BZ-resistance (BZ-R) in ascarids are rare, but we recently reported BZ-R in two ascarid species of poultry (Ascaridia dissimilis and Heterakis gallinarum) for the first time. We performed whole-genome sequencing to determine if any of the strongylid BZ-R alleles were present in these ascarids. Illumina short-read and PacBio long-read sequencing were carried ...
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Conférences

le (8m51s)

Frida Martin - Exploring the β-tubulin gene family in a benzimidazole-resistant Parascaris univalens population.

Benzimidazole (BZ) resistance is rare in ascarids in contrast to strongyle parasites where this resistance is widespread. In strongyles, single nucleotide polymorphisms (SNPs) at codons 167, 198 and 200 in a β-tubulin gene have been correlated to BZ resistance, but little is known about the β-tubulin genes and their possible involvement in BZ resistance in P. univalens and other ascarids. Previously two β-tubulin genes were identified in P. univalens. Here, we present five additional β-tubulin genes as well as the phylogenetic relationship of all seven genes to β-tubulins of other clade III and V nematodes. In addition, the efficacy of ...
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Conférences

le (19m18s)

Prof. Georg von Samson-Himmelstjern - Functional analysis of heterologous expression of Parascaris univalens P-glycoprotein in C. elegans

This presentation will provide an overview on recent investigations concerning the P-glycoprotein gene family in the equine roundworm Parascaris univalens. As prominent members of the ATP-Binding-Cassette (ABC) transmembrane transporters, Pgps are considered to play an important role in the expulsion of xenobiotic substances in many different organisms including parasitic nematodes. Compared with the situation in mammals the genome of nematodes includes a large number of different Pgp-genes, with e.g. P. univalens exhibiting ten Pgp-genes including some apparently ascarid specific orthologues. The specific significance of these genes for instance concerning anthelmintic drug transport is thus far largely unresolved. To contribute further ...
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Conférences

le (13m44s)

Dr Cédric Neveu - Investigating anthelmintic molecular targets of Ascarids using C. elegans as a model: pros and cons

Despite their large diversity, most of the nematode species are susceptible to broad spectrum anthelmintics. In that respect, it is tempting to speculate that extensive C. elegans data about molecular anthelmintic targets could lay strong basis to investigate their counterparts in phylogenetically distantly related nematode species such as Ascarids.In the present talk, Parascaris univalens studies focussing on Morantel and macrocyclic lactones pharmacological targets will be used as examples to highlight some limitation of C. elegans as a model for Ascarids. Potential alternatives to C. elegans and new prospects concerning the adaptation (to Ascarids) of recently developed technologies for both drug ...
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Conférences

le (11m31s)

Dr Behdad Tarbiat -Allele frequency shift in the β-tubulin gene of Ascaridia galli in response to repeated exposure to fenbendazole

Despite global spread of anthelmintic resistance in livestock, there has been little discussion about the development of AR in poultry. Ascaridia galli has become ubiquitous in layers due to the ban on battery cages which has led to increase in anthelmintic use. Rapid changes in the pattern of anthelmintic use in poultry may impose strong selective pressures on A. galli. This study was set out to investigate the genetic changes of the β-tubulin gene upon repeated exposure to BZ. Worm population with 0-, 1- and 3-times exposure (TT) to BZ was acquired. Parasite DNA was extracted, and three β-tubulin candidate ...
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Conférences

le (12m5s)

Prof. Adrian Wolstenholme - C. elegans as a model for ascarid parasites; levamisole receptors

Ligand-gated ion channels provide an excellent test for any expression system and for C. elegans as a model for parasitic nematode species, including the ascarids. They are complex proteins made of multiple subunits which are encoded by a large gene family, that carry multiple post-translational modifications and which exhibit varied physiological and pharmacological properties. This last property makes them excellent drug targets and provides a fairly simple way of testing the accuracy of any comparison between native and recombinant channels. The levamisole receptor is an excellent illustration; in C. elegans full expression of a levamisole-sensitive receptor in Xenopus oocytes is ...
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Conférences

le (10m6s)

Ben Jones - Disentangling the role of Ascaris β-tubulin isotypes in the emergence of anthelmintic resistance

Ascariasis affects nearly one billion people, predominantly in the developing world. Ascariasis also affects pigs globally and reduces production yields via decreased growth and condemnation of livers. The predominant drugs used to treat ascariasis are the benzimidazoles (BZ). Despite using BZ anthelmintics for decades and BZ resistance occurring in other helminths, there has been little work on resistance in pig ascariasis. Benzimidazoles work by interacting with β-tubulin and the mutations causing resistance are known in some nematodes. Seven β-tubulin isotypes were identified using Ascaris genome data, and expression profiles were analysed at various developmental stages. Only three of the seven ...
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