Details of Award
NERC Reference : NE/R008183/1
Worms, sheep and environment: integrating ecological perspectives into resistance management
Training Grant Award
- Lead Supervisor:
- Professor BK Mable, University of Glasgow, College of Medical, Veterinary, Life Sci
- Grant held at:
- University of Glasgow, College of Medical, Veterinary, Life Sci
- Science Area:
- Terrestrial
- Overall Classification:
- Terrestrial
- ENRIs:
- Biodiversity
- Environmental Risks and Hazards
- Science Topics:
- Livestock
- Sustainable agriculture
- Agricultural systems
- Parasitology
- Parasitology
- Adaptation
- Evolution & populations
- Abstract:
- Resistance management is a key concern in human and veterinary medicine and in agricultural production systems. Although theoretical population genetics models predict factors expected to influence resistance evolution, interactions among pathogen attributes (e.g. mating system, life history traits, rate of gene flow between resistant and susceptible genotypes), host traits (e.g immunity, migration), and the strength of selection imposed by specific control measures (e.g., frequency and dosage of chemical applications, strategies for maintaining refugia for susceptible individuals) have not been widely studied. However, there is increasing recognition that managing pests and parasites can be most efficient if their environment is altered, rather than just attempting control with chemical treatments of their hosts. A previous NERC studentship demonstrated the utility of incorporating ecological perspectives when predicting rates of resistance evolution. Using an experimental evolution approach involving free-living nematodes as a model (Caenorhabidtis remanei), the student revealed that apparent development of resistance to a commonly used anthelmintic (ivermectin) was likely due to density-dependent changes in life history strategies (e.g. selection for larger worms that develop faster and are more tolerant to the drugs), rather than heritable genetic changes in resistance allele frequencies. Intriguingly, a recent genome-wide association study of resistance to ivermectin in parasitic nematodes of sheep (Haemonchus contortus), conducted by members of the proposed supervisory team, revealed a signature that is consistent with polygenic inheritance, as might be expected for life-history associated changes. Moreover, the genomic analysis confirmed previous suggestions that the parasites are polyandrous, with up to 8 male parents necessary to explain the variation observed in a brood of larvae raised from eggs from a single female. Finally, there were differences in phenotypes of reciprocal crosses, in terms of the relative strength of resistance and dominance of responses to different anthelmintics. While more challenging because of the need to propagate worms in live sheep, this project demonstrates the feasibility of applying genomic approaches to assessing life history related effects and reproductive modes even in parasites. However, this has only been possible due to a large-scale collaboration between parasitologists, geneticists, veterinarians, farmers, bioinformaticians, statisticians and modellers. The purpose of the proposed studentship is to continue to integrate these perspectives but to take a more ecological approach to interpreting implications for parasite control. Specifically, they will work with the CASE partner (Moredun Scientific) to study the available genetic crosses of H. contortus, generated from genetically divergent parental isolates differing in anthelmintic sensitivity. In addition to further characterising the genetic basis of ivermectin resistance, they will investigate life history traits associated with resistance and establish whether resistant individuals also differ from susceptibles in morphological phenotypes. They will work with both the CASE partner and the academic researchers to test how changes in the selective environment affect the development of resistance in both parasitic and free-living nematodes. In addition to this more prescribed research based on optimised methods, there is substantial scope to allow the student flexibility to take the project in research directions that reflect their own specific interests and aptitudes. For example, the research consortium of which they would be a part (the BUG consortium) also involves mathematical modellers, who could be officially added to the supervisory team. The student would thus benefit from truly multidisciplinary training and the capacity for development of independent research trajectories.
- NERC Reference:
- NE/R008183/1
- Grant Stage:
- Completed
- Scheme:
- DTG - directed
- Grant Status:
- Closed
- Programme:
- Industrial CASE
This training grant award has a total value of £89,114
FDAB - Financial Details (Award breakdown by headings)
| Total - Fees | Total - Student Stipend | Total - RTSG |
|---|---|---|
| £17,480 | £60,637 | £11,000 |
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