Inositol metabolism in euryhaline teleosts: roles in osmoregulation and disruption by organic pesticides

Lead Research Organisation: University of St Andrews
Department Name: Sch of Medicine


The evolutionary success and survival of aquatic organisms in many diverse freshwater (FW) and sea water (SW) habitats has been made possible by the development of complex interrelated ion and water transport systems which allow animals and plants to osmoregulate and survive in extreme hypotonic and hypertonic environments. Well-studied examples of this are the euryhaline teleosts, such as the European eel and the Atlantic salmon, which exhibit the genetic plasticity to enable survival in both FW and SW with only minimal changes in the osmolality and ionic composition of their body fluids. In order to accomplish this, euryhaline teleosts have evolved the capacity to adapt their osmoregulatory strategies to allow the excretion of excess water and the scavenging of salts from ion-poor FW habitats while reversing these functions when entering SW. Recent evidence has suggested that the simple organic alcohol, inositol, is central to the ability of eels to adapt to SW environments. This polyol, which is synthesised and accumulated in a variety of tissues such as the gill, skin and fins, acts in many hormonal signalling pathways and also as an organic osmolyte, preventing the osmotic loss of water and the subsequent desiccation of fish when in SW. Body surface epithelial cells, which accumulate inositol can then act as a barrier between the hypo-osmotic internal environment of the fish and the hyperosmotic external environment.

This project will investigate the expression and function of genes involved in inositol production and distribution in two model species, the eel and the salmon, to determine the roles of this osmolyte in both FW- and SW-adapted teleosts. Although both eel and salmon are capable of movement between FW and SW, the physiological patterns of salinity adaptation are slightly different. Although sexually immature FW "yellow" eels can successfully acclimate to acute transfers to SW, the sexually immature FW salmon parr must first go through an endocrine-induced maturation process called smoltification before fish can survive in SW. The ability of mature and immature life stages of both eels and salmon to regulate inositol production in response to increased environmental salinities will be investigated as will the effects of cortisol, a hormone known to be involved in sexual maturation and salinity adaptation in fish.

In addition we have recently discovered that an essential enzyme responsible for the cellular production of inositol, inositol monophosphatase (IMPA), can be inhibited or in some cases stimulated by low concentrations of a wide range of organic toxins known to be found in FW. Any perturbations in the activity of this key enzyme by any environmental toxins are likely to have profound effects on the subsequent ability of fish to osmoregulate. Recent evidence suggests that enzymatic activity of IMPA is inhibited by an unknown protein component(s) of the cytoskeleton, and that at least some stimulatory toxins appear to disrupt this normal regulatory system. Potential deleterious effects of toxins on osmoregulation and hormonal signalling could be associated with over-stimulation of the enzyme when fish are in FW and/or inhibition of the enzyme after fish migrate to SW. Such perturbations would certainly compromise the ability of fish to osmoregulate and this is likely to have severe implications with respect to fish migration and the overall fecundity of the species. Over the last 30 years there has been dramatic declines in both salmon and in eel populations. Although the reasons for the decrease in the populations of both species are undetermined, exposures of fish to a variety of anthropogenic toxins have been implicated in a number of studies. This project will determine if any of the major persistent environmental toxins have any effects on the enzymes responsible for the production and tissue distribution of this essential organic osmolyte and signalling molecule.

Planned Impact

The pathway to impact plan will use a multi- faceted approach based on our current strategy of inclusive end-user engagement. A key component is to continue to disseminate information through a project-specific website (for example see the SUMBAWS website ). We will develop a new website in parallel to the existing SUMBAWS site and, where relevant, linked to it. This will allow direct access to the extensive international network that has been built up as a result of the SUMBAWS programme. Publication of findings will be in journals with the highest impact factors possible within the research area (FASEB J., Am. J. Physiol., J. Exp. Biol., J. Endocr. and Gen. Comp. Endocr.). Particular attention will be given to include publication in open access journals to ensure freedom of access (e.g. the "ACS AuthorChoice" option facilitates unrestricted web access to an article in Env. Sci. and Tech., BMC Biology and PlosBiology). Sequence data will be submitted to public databases such as EBI, the Gene Pool Consortium, Eelbase (, Eeelbase ( and NERC EnvBase ( envbase-introduction).
The scientists involve in this project have substantial collaboration and interactions with existing and established partner organizations in Europe (NINA and NIFA in Norway, CFB in Ireland, the European Anguilla Genome Consortium organised by Maes (Leuven) and Zane (Padua), the EELIAD project; whose work relates strongly to the management of wild fisheries and who give substantial Government advice. We will build upon our experience of workshop organization with end-users and organize an international workshop in the 2nd year of the project utilizing the annual SEB Conference as a platform as this conference already attracts the majority of academic scientists within this research area. Using the SEB meeting will be both cost and time effective employing the existing SEB conference infrastructure for organizing, advertising and delivery of the workshop. The workshop will be at an international (European) level as we have already established a community of researchers partly as a result of the SUMBAWS network at the European level. A central requirement of this workshop will be to invite all relevant government scientists, those setting Public Policy and Legislation and non-governmental organizations. The timing of the workshop will be important as it will be at a stage when sufficient data will be available to inform on the initial results regarding expression studies in the different species and the impacts of specific organic pesticides but leaving scope for minor modifications to the work programme in the final year based upon workshop discussions. It will also have the potential of expanding the studies through additional follow-up studies with our European partners.
Our aim is to communicate our science to the widest possible audience and at every opportunity. This will involve wherever possible the use of the media (e.g. we have participated in a television documentary based on our NERC supported studies on elasmobranch fish made by Australian Television). This documentary aimed to educate the public with regard to the unjustified and sometimes illegal exploitation of shark species. In this respect we will ensure that the postdoctoral researcher attends the NERC "Communicating science to the public" course in order to become fully trained to participate and interact with media events and opportunities. The applicants are in a supportive environment to end-user engagement since the University of St Andrews has established Committees to facilitate and enhance Research and Knowledge transfer. This includes a series of scientific open days and scientific presentations organised by the University for the General Public in which the key findings of the proposed study will be presented.


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Description Although progress on the grant has has been delayed due to a severe staffing problem, the reserach has led to the discovery of yet another osmolyte that appears to be specific in salmonids. Recent evidence suggests that this osmolyte is not only essential for successful osmoregulation of smolts in seawater, but appears to be a component of a novel innate immune response in salmon skin and fin. This has recieved much interest from a number of companies associated with the salmon aquaculture industry who have part-funded a Ph D student to investigate and characterise organic osmolytes in salmonid tissues. The work on the effect of environmental toxins and inositol metabolism in the eel (and also tilapia) is on-going.
First Year Of Impact 2013
Sector Agriculture, Food and Drink,Environment,Other
Impact Types Economic

Description EWOS Innovation 
Organisation University of Oxford
Department Oxford University Innovation
Country United Kingdom 
Sector Private 
PI Contribution Research into the effects of certain nutritional additives on the efficiency of osmoregulation of salmon smolts when moved to seawater.
Collaborator Contribution Provision of animals, materials and in house facilities to mediate our research
Impact None as yet
Start Year 2010
Description Marine Harvest (Scotland) 
Organisation Marine Harvest
Country Norway 
Sector Private 
PI Contribution Conducting research in an area that has potential to discover a new biomearker of smoltification in the salmon aquaculture industry.
Collaborator Contribution Provision of fish and on-site facilities for small scale experimentation.
Impact So far outputs have been limited to presentations at national and international conferences. Full publications are currently in preparation.
Start Year 2008
Description Osmolyte characterisation in teleost fish 
Organisation University of Washington
Country United States 
Sector Academic/University 
PI Contribution Included my collaborator in scientific publications and provided experimental samples for his reaserch
Collaborator Contribution Analyzed samples for the levels of metabolites and osmolytes
Impact publication: Kalujnaia, S., Gellatly, S.A., Hazon, N., Villasenor, A., Yancey, P.H. and Cramb, G. (2013) Seawater acclimation and inositol monophosphatase (IMPA) isoform expression in the European eel (Anguilla anguilla) and Nile tilapia (Orechromis niloticus). Am. J. Physiol. 305: R369-R348. (doi: 10.1152/ajpregu.00044.2013)
Start Year 2009