Project description:A. simplex s.s. (parasitic nematode) under the in vitro treatment with different concentrations of lipopolysaccharide (LPS) of Escherichia coli. Complete TMT10plex labeling. LC-MS/MS analysis.
Project description:We present the first study to confirm the existence of DNA methylation in the parasitic nematode Trichinella spiralis, and we characterize the methylomes of the three life-cycle stages of this food-borne infectious human pathogen. We observe a drastic increase in DNA methylation during the transition from the new born to mature stage, and we further identify parasitism-related genes that show changes in DNA methylation status between life cycle stages. We also evaluated differential gene expression among the three life stages using Illumina HiSeq 2000 RNA-seq technology.
Project description:Within the context of our anthelmintic discovery program, we recently identified and evaluated a quinoline derivative, called ABX464 or obefazimod, as a nematocidal candidate; synthesised a series of analogues which were assessed for activity against the free-living model nematode Caenorhabditis elegans; and predicted compound-target relationships by thermal proteome profiling (TPP) and in silico docking. Here, we logically extend(ed) this work and critically evaluate(d) the anthelmintic activity of ABX464 analogues on Haemonchus contortus (barber’s pole worm) – a highly pathogenic nematode of ruminant livestock. First, we tested a series of 44 analogues on H. contortus (larvae and adults) to investigate ABX464’s nematocidal pharmacophore, and identified one compound with greater potency than the parent compound, and also showed moderate activity against a select number of other parasitic nematodes (including Ancylostoma, Heligmosomoides and Strongyloides species). Using TPP and in silico modelling studies, we predicted protein HCON_00074590 (a predicted aldo-keto reductase) as a target candidate for ABX464 in H. contortus. Future work aims to optimise this compound as a nematocidal candidate and investigate its pharmacokinetic properties. Overall, this study presents the first steps towards the development of a new anthelmintic with a novel, distinct mechanism of action.
Project description:N-glycosylation is a physiologically vital post-translational modification of proteins in eukaryotic organisms. Initial work on Haemonchus contortus – an economically-important blood-sucking nematode of ruminants with a broad geographical distribution – has shown that the parasite harbors N-glycans with exclusive core chitobiose modifications, and severel immunogenic proteins (e.g., amino- and metallo-peptidases) in the adult worms are N-glycosylated. However, an informative atlas of N-glycosylation in H. contortus is not yet available. Herein, we report a total of 291 N-glycosylated proteins with 425 sites in this parasite. Functional analyses of glycoproteome revealed significant enrichment of the peptidase families (e.g., peptidase C1 and M1), many of which are potential vaccine targets. Besides, the glycan-rich conjugates are distributed primarily in the intestine and gonads of the adult worms. These data, taken together, provide a comprehensive insight into the N-glycosylation of a prevalent parasitic nematode, while underlining its significance for the infection and prophylaxis.
Project description:This investigation was designed to follow the parasitic fungus Monacrosporium haptotylum during infection of the nematode Caenorhabditis elegans. M. haptotylum traps nematodes using a spherical structure called knob, which develops on the apex of a hyphal branch. The advantage of using this species is that the unicellular knobs can be separated from the mycelium that has been grown in liquid culture. The isolated knobs retain the function as infection structures. The cDNA microarray contained 2,778 M. haptotylum and 588 C. elegans gene reporters. The experiments was designed as a time course study including infected and non-infected tissue, over 24 hours which involves stages of adhesion, penetration and digestion of the infected nematodes.
Project description:Bio-electrospray, the direct jet-based cell handling apporach, is able to handle a wide range of cells. Studies at the genomic, genetic, and the physiological level have shown that, post-treatment, cellular integrity is unperturbed and a high percentage (>70%, compared to control) of cells remain viable. Although, these results are impressive, it may be argued that cell based systems are oversimplistic. This study utilizing a well characterised multicellular model organism, the non-parasitic nematode Caenorhabditis elegans. Nematodes were subjected to bio-electrosprays to demonstrate that bio-electrosprays can be safely applied to nematodes.
Project description:Expression profiling of 7,530 Heterodera glycines probesets present on the Affymetrix Soybean Genome Array GeneChip throughout the life cycle of the nematode (egg, infective J2, parasitic J2, J3, J4, adult female).
