Periodic Reporting for period 1 - SeaWeedWorm (Discovering how bioactive compounds from seaweed kill parasitic worms)
Berichtszeitraum: 2023-08-14 bis 2025-08-13
Parasitic nematode infections are a major constraint on sustainable livestock production worldwide, causing significant economic losses, compromising animal welfare, and increasing dependence on chemical anthelmintic drugs. The rapid and widespread emergence of resistance to all major anthelmintic classes has created an urgent need for novel, sustainable, and low-residue parasite control strategies, aligning directly with European priorities on sustainable agriculture, reduced chemical inputs, and resilient food systems. Natural bioactive compounds have emerged as promising alternatives to synthetic drugs. Polyunsaturated fatty acids (PUFAs) derived from seaweeds have shown anthelmintic activity against parasitic nematodes. However, prior to this project, their mechanisms of action were poorly understood, limiting rational optimisation and safe application in animal health systems. Addressing this mechanistic gap was essential for enabling translation of PUFA-based strategies into sustainable parasite control solutions.
The overall objective of the SeaWeedWorm project was to elucidate the mechanistic basis of PUFA-induced nematode toxicity using the genetically tractable model organism Caenorhabditis elegans. By integrating phenotypic, ultrastructural, transcriptomic, and functional approaches, the project aimed to move beyond descriptive observations and provide systems-level insight into how PUFAs disrupt nematode biology.
Specifically, the project sought to:
• Characterise phenotypic and structural effects of PUFAs on nematodes.
• Identify molecular pathways perturbed by sub-lethal PUFA exposure; and
• Functionally validate key cellular processes affected, particularly those linked to mitochondrial function and stress responses.
The pathway to impact envisaged was mechanistic discovery leading to biological understanding and longer-term translational potential. By identifying conserved cellular pathways targeted by PUFAs, the project generated foundational knowledge to support the development of sustainable anthelmintic strategies, including bioactive feeds, nutraceuticals, and lead compounds for drug discovery. Although pre-translational, the outcomes are directly relevant to agricultural, environmental, and industrial needs.
Overall, the project addresses a global livestock health challenge with implications for food security, environmental sustainability, and animal welfare, and contributes to European and international efforts to promote resilient and environmentally responsible livestock systems.
The overall objective of the SeaWeedWorm project was to elucidate the mechanistic basis of PUFA-induced nematode toxicity using the genetically tractable model organism Caenorhabditis elegans. By integrating phenotypic, ultrastructural, transcriptomic, and functional approaches, the project aimed to move beyond descriptive observations and provide systems-level insight into how PUFAs disrupt nematode biology.
Specifically, the project sought to:
• Characterise phenotypic and structural effects of PUFAs on nematodes.
• Identify molecular pathways perturbed by sub-lethal PUFA exposure; and
• Functionally validate key cellular processes affected, particularly those linked to mitochondrial function and stress responses.
The pathway to impact envisaged was mechanistic discovery leading to biological understanding and longer-term translational potential. By identifying conserved cellular pathways targeted by PUFAs, the project generated foundational knowledge to support the development of sustainable anthelmintic strategies, including bioactive feeds, nutraceuticals, and lead compounds for drug discovery. Although pre-translational, the outcomes are directly relevant to agricultural, environmental, and industrial needs.
Overall, the project addresses a global livestock health challenge with implications for food security, environmental sustainability, and animal welfare, and contributes to European and international efforts to promote resilient and environmentally responsible livestock systems.
During the reporting period, the project focused on elucidating the mechanistic basis of PUFA anthelmintic activity using C. elegans. The work integrated phenotypic assays, ultrastructural analyses, transcriptomics, and functional validation, enabling a multi-level investigation of PUFA-induced toxicity.
Work performed
The experimental work comprised three main components:
1. Phenotypic and ultrastructural characterisation
Egg hatch inhibition and larval mortality assays were performed to assess ovicidal and larvicidal effects of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and linoleic acid. Scanning electron microscopy was used to examine ultrastructural damage in embryos and larvae.
2. Transcriptomic profiling
RNA sequencing was conducted on C. elegans exposed to sub-lethal concentrations of ALA and EPA. Differential gene expression and pathway enrichment analyses identified biological processes perturbed by PUFA exposure.
3. Functional validation
Functional assays validated transcriptomic findings, focusing on mitochondrial function and cellular stress responses, including mitochondrial membrane potential, reactive oxygen species production, and protein aggregation.
Main achievements
Key scientific outcomes include:
• Demonstration of compound-specific anthelmintic activity, with ALA consistently showing more substantial ovicidal and larvicidal effects than EPA and linoleic acid.
• Identification of developmental and structural phenotypes, including embryonic arrest, abnormal larval morphology, and cuticular disruption.
• Generation of high-quality transcriptomic datasets revealing perturbation of lipid metabolism, mitochondrial function, oxidative stress, detoxification, and longevity-related pathways.
• Functional validation of mitochondrial dysfunction and cellular stress, particularly in response to ALA.
Together, these achievements provide a robust mechanistic foundation for future translational research on sustainable parasite control and natural-product-based anthelmintics.
Work performed
The experimental work comprised three main components:
1. Phenotypic and ultrastructural characterisation
Egg hatch inhibition and larval mortality assays were performed to assess ovicidal and larvicidal effects of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and linoleic acid. Scanning electron microscopy was used to examine ultrastructural damage in embryos and larvae.
2. Transcriptomic profiling
RNA sequencing was conducted on C. elegans exposed to sub-lethal concentrations of ALA and EPA. Differential gene expression and pathway enrichment analyses identified biological processes perturbed by PUFA exposure.
3. Functional validation
Functional assays validated transcriptomic findings, focusing on mitochondrial function and cellular stress responses, including mitochondrial membrane potential, reactive oxygen species production, and protein aggregation.
Main achievements
Key scientific outcomes include:
• Demonstration of compound-specific anthelmintic activity, with ALA consistently showing more substantial ovicidal and larvicidal effects than EPA and linoleic acid.
• Identification of developmental and structural phenotypes, including embryonic arrest, abnormal larval morphology, and cuticular disruption.
• Generation of high-quality transcriptomic datasets revealing perturbation of lipid metabolism, mitochondrial function, oxidative stress, detoxification, and longevity-related pathways.
• Functional validation of mitochondrial dysfunction and cellular stress, particularly in response to ALA.
Together, these achievements provide a robust mechanistic foundation for future translational research on sustainable parasite control and natural-product-based anthelmintics.
The project advances the state of the art by providing mechanistic, systems-level insight into how PUFAs, particularly ALA, disrupt nematode biology.
Key advances include:
• Ovicidal and developmental effects, demonstrating embryonic arrest and early developmental disruption, extending understanding beyond larval or adult lethality.
• Mechanistic differentiation between PUFAs, showing that PUFAs are not functionally equivalent and must be evaluated on a compound-specific basis.
• Integrated mechanistic evidence, linking phenotypic damage, ultrastructural changes, transcriptomic responses, and functional stress phenotypes.
• Identification of conserved cellular pathways affected by PUFA exposure, supporting a polypharmacological mode of action distinct from single-target anthelmintics.
These findings position PUFAs as mechanistically distinct bioactives with potential advantages for sustainable parasite control and resistance management.
Indicative impacts and pathways to uptake
While pre-translational, the results provide a strong foundation for future impact. Further research is required to validate findings in parasitic nematodes and production systems, optimise formulations and delivery routes, and align with regulatory frameworks governing feed additives, nutraceuticals, or veterinary medicines. Given the global nature of anthelmintic resistance, the outcomes are relevant beyond Europe and support international efforts toward sustainable, low-residue parasite control.
Key advances include:
• Ovicidal and developmental effects, demonstrating embryonic arrest and early developmental disruption, extending understanding beyond larval or adult lethality.
• Mechanistic differentiation between PUFAs, showing that PUFAs are not functionally equivalent and must be evaluated on a compound-specific basis.
• Integrated mechanistic evidence, linking phenotypic damage, ultrastructural changes, transcriptomic responses, and functional stress phenotypes.
• Identification of conserved cellular pathways affected by PUFA exposure, supporting a polypharmacological mode of action distinct from single-target anthelmintics.
These findings position PUFAs as mechanistically distinct bioactives with potential advantages for sustainable parasite control and resistance management.
Indicative impacts and pathways to uptake
While pre-translational, the results provide a strong foundation for future impact. Further research is required to validate findings in parasitic nematodes and production systems, optimise formulations and delivery routes, and align with regulatory frameworks governing feed additives, nutraceuticals, or veterinary medicines. Given the global nature of anthelmintic resistance, the outcomes are relevant beyond Europe and support international efforts toward sustainable, low-residue parasite control.