Knowledge Transfer -Impacts of inbreeding on the responses to pharmaceuticals and fitness consequences in fish - a molecular approach

Pharmaceuticals in the environment potentially have wide reaching deleterious impacts on wildlife and possibly humans, and are at the top of the Environment Agency's agenda for environmental pollution. Population level declines in wildlife have resulted from exposure to pharmaceuticals (e.g. diclofenac in vultures in Asia). Furthermore, some reproductive disorders associated in humans are now a major health issue and parallel those effects seen in wildlife that have been associated with exposure to environmental chemicals, including pharmaceuticals. The UK holds a strong lead in the field of pharmaceuticals in the aquatic environment and the applicants have contributed to the unfolding explanation of how some such contaminants interfere with normal reproductive activity in fish. . Information on interactive effects of inbreeding and pollutant exposure is extremely limited and essentially nothing is known for pharmaceuticals, which is surprising given that inbred strains of animals are used most commonly for laboratory testing of chemicals, including pharmaceuticals. This project will provide an understanding of the vulnerability or resistance of inbred populations of fish for exposure to the pharmaceutical,ketoconazole (a synthetic antifungal drug employed as an agricultural pesticides and clinically to prevent and treat skin and fungal infections), as a representative of a group of widely used group of fungicides. The use of genome-wide approaches (gene arrays) will enable us to dissect out gene expression networks most intimately associated with physiological stress for exposure to this pharmaceutical. The data from the project will further provide insights into the critical determinants of vulnerability of fish to a pharmaceutical of importance to human health. The data on the comparative responses to ketoconazole in inbred and outbred populations and impacts on breeding dynamics will also be highly informative for ecological and environmental risk assessment. This proposal will thus provide new information on gene-environment interactions for chemical exposure effects in fish. The project is also likely to deliver a more informative set of biological (molecular) effects tools upon which to base environmental impact and health assessments for ketoconazole and other allied fungicides. This work will provide substantive information on the health impacts of ketoconazole in the natural environment for the better protection of our aquatic resources and biodiversity and will contribute more widely to environmental impact assessments and will thus be of very wide interest to the government regulatory bodies, environment protection groups, industry and the wider public. A key element of the project is an enhancement in the partnership between academia (University of Exeter) and an end-user (Astrazeneca). This partnership will facilitate the uptake of genetic and genomic methods for chemical hazard identification (and developed through NERC funded science) into the pharmaceutical industry. It will further facilitate an enhanced understanding in academia of the practical research needs of the chemical/pharmaceutical industry.