Dataset Information

Evaluation of serum supplementation on the development of Haemonchus contortus larvae in vitro and on compound screening results

ABSTRACT: A high-throughput platform for assessing the activity of synthetic or natural com-pounds on the motility and development of Haemonchus contortus larvae has been estab-lished for identifying new anthelmintic compounds active against strongylid nema-todes. This study evaluated the impact of serum supplementation on larval develop-ment, motility and survival in vitro and its implications for phenotypic compound screening. Of five blood components assessed, 7.5% sheep serum significantly enhanced larval development, motility and survival compared with the original medium (LB*), leading to the formulation of an improved medium (LBS*). Proteomic analysis revealed marked differences in protein expression in larvae cultured in LBS* versus LB*, includ-ing molecules associated with structural integrity and metabolic processes. The pheno-typic screening of 240 compounds (“Global Priority Box” from Medicines Malaria Ven-ture) using LBS* yielded results distinct from those in LB*, highlighting the effect of culture conditions on screening assessments. These findings indicate/emphasise the critical need to evaluate and optimise culture media for physiologically conditions in screening platforms, improving the reliability of anthelmintic discovery.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Haemonchus Contortus (barber Pole Worm)

TISSUE(S): Stem Cell, Whole Body

DISEASE(S): Parasitic Infectious Disease

SUBMITTER: Tao Wang

LAB HEAD: Robin B. Gasser

PROVIDER: PXD060092 | Pride | 2025-02-27

REPOSITORIES: pride

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Evaluation of Serum Supplementation on the Development of <i>Haemonchus contortus</i> Larvae In Vitro and on Compound Screening Results.

Thilakarathne Sandani S SS Taki Aya C AC Wang Tao T Nowell Cameron C Chang Bill C H BCH Gasser Robin B RB

International journal of molecular sciences 20250128 3

A high-throughput platform for assessing the activity of synthetic or natural compounds on the motility and development of <i>Haemonchus contortus</i> larvae has been established for identifying new anthelmintic compounds active against strongylid nematodes. This study evaluated the impact of serum supplementation on larval development, motility and survival in vitro and its implications for phenotypic compound screening. Of five blood components assessed, 7.5% sheep serum significantly enhanced ...[more]

PMID: 39940885

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Project description:Huntington’s disease is a fatal autosomal dominant neurodegenerative disorder, characterized by neuronal cell loss, primarily in the striatum, cortex, and hippocampus, causing motor, cognitive, and psychiatric impairments. Unfortunately, no treatments are yet available to modify the progression of the disease. Recent evidence from Huntington’s disease mouse models suggests that protein phosphorylation (catalysed by kinases and hydrolysed by phosphatases) might be dysregulated, making this major posttranslational modification a potential area of interest to find novel therapeutic targets. Furthermore, environmental enrichment (EE), used to model an active lifestyle in preclinical models, has been shown to alleviate Huntington’s disease-related motor and cognitive symptoms. However, the molecular mechanisms leading to these therapeutic effects are still largely unknown. In this study, we applied a phosphoproteomics approach combined with proteomic analyses on brain samples from pre-motor symptomatic R6/1 Huntington’s disease male mice (HD mice) and their wild-type (WT) littermates, after being housed either in EE conditions, or in standard housing (SH) conditions from 4 to 8 weeks of age (n=6 per group). We hypothesised that protein phosphorylation dysregulations occur prior to motor onset in this mouse model, in two highly affected brain regions, the striatum and hippocampus. Furthermore, we hypothesised that these phosphoproteome alterations are rescued by EE. When comparing 8-week-old HD mice and WT mice in SH conditions, our analysis revealed 229 differentially phosphorylated peptides in the striatum, compared to only 15 differentially phosphorylated peptides in the hippocampus (statistical thresholds FDR0.05, FC1.5). At the same disease stage, minor differences were found in protein expression, with 24 and 22 proteins dysregulated in the striatum and hippocampus, respectively. Notably, we found no differences in striatal protein phosphorylation and protein expression when comparing HD mice and their WT littermates in EE conditions. In the hippocampus, only four peptides were differentially phosphorylated between the two genotypes under EE conditions, and 22 proteins were differentially expressed. Together, our data indicates that protein phosphorylation dysregulations occur in the striatum of HD mice, prior to motor symptoms, and that the kinases and phosphatases leading to these changes in protein phosphorylation might be viable drug targets to consider for this disorder. Furthermore, we show that an early environmental intervention was able to rescue the changes observed in protein expression and phosphorylation in the striatum of HD mice and might underlie the beneficial effects of EE, thus identifying novel therapeutic targets.

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Dataset Information

Evaluation of serum supplementation on the development of Haemonchus contortus larvae in vitro and on compound screening results

Dataset's files

Publications

Evaluation of Serum Supplementation on the Development of <i>Haemonchus contortus</i> Larvae In Vitro and on Compound Screening Results.

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Dataset Information

Evaluation of serum supplementation on the development of Haemonchus contortus larvae in vitro and on compound screening results

Dataset's files

Publications

Evaluation of Serum Supplementation on the Development of &lt;i&gt;Haemonchus contortus&lt;/i&gt; Larvae In Vitro and on Compound Screening Results.

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OmicsDI is part of the ELIXIR infrastructure

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Evaluation of Serum Supplementation on the Development of <i>Haemonchus contortus</i> Larvae In Vitro and on Compound Screening Results.