My research group integrates molecular, physiological and toxicological techniques to understand and predict responses to natural and man-induced stressors. Currently two novel approaches to this research are being pursued.

• Metal homeostasis and toxicity
• Iron and zinc metabolism

Recently, we have shown that freshwater fish are able to acquire iron from water and that marine fish acquire iron from their diet. This is of significance as in both environments; iron would not be expected to be bioavailable in significant quantities. This is because in well oxygenated circumneutral freshwaters, iron is predominantly bound into insoluble ferric (hydro)oxides and in marine fish, secretion of large amounts of bicarbonate in the intestine would be predicted to chelate divalent ions. The specialised mechanisms by which the gills and gut of fish are able to acquire iron is the focus of current investigations.

In addition, we are currently exploring how stress influence cellular zinc uptake, signalling and buffering.

Metal toxicity

Maintaining essential metal homeostasis and excreting non-essential metals when exposed to elevated metals in the environment are important for health. Recently, we have shown that diets with elevated concentrations of metals do impair reproductive performance in fish. What is of interest is that these contaminated diets were natural, comprising polychaetes from estuaries with a history of elevated concentrations of metal mixtures. However, the only element to be implicated in the toxicity was arsenic. This result is of interest to researchers throughout the world who are assessing the contribution dietary metals make to the overall ecological impact of metal pollution. We are currently assessing metal assimilation efficiency in dietary-exposed fish and linking this to metal homeostasis by measuring the changes in the expression of the key metal transport proteins (DMT, CTR1, Zip, IREG, ZnT1) in epithelial tissues

Gill cell culutre - The gills of fish are constantly bathed in water and are thus always exposed to pollutants. We have developed;technique to culture gill cells on permabale supports;enabling water to be placed the outside and media on the inside. Thus, mimicking the exposure route for fish. This system has been shownto mimic the resposne of whole organisms tometal pollution. Two new projects will test theversatiltiy of this system. The first will determine if it repsonds well to natural waters and thus can be used in investigative pollution monitoring programmes. The second will assess the response of the cells to a suite of pharmaceuticals. The aimis assess if this cell based system can replace the large numbers of fish that are currently used in toxicity testing experiments.

Corticosteriod receptor functioning and evolution

In mammals there are two corticosteroid receptors (CRs), glucocorticoid (GRs) and mineralocorticoid (MRs) receptors that control or influence a vast array of cellular functions. For example they are involved in the stress response, mineral balance, immune system and development. We have recently made an intriguing discovery - teleost fish have two GRs and an MR, the extra GR apparently being retained following the whole genome duplication that occurred in the actinopterygian lineage around 350MYA. These two receptors have very differing sensitivities in transactivation studies to cortisol, the main corticosteroid hormone in fish. This suggests a mechanism for neofunctionalisation of the duplicated GR. We are currently identifying the molecular basis for this difference in sensitivity, as this may be an important feature relating to the evolution of GR and MR characteristics in the early actinopterygians and teleost fish.