Prioritised expression of stress-related proteins in environmental thermoadaptive responses of animals

Underpinning the assumptions and models of how climate will affect natural populations are expectations of how the predicted temperature change affects the life history, fecundity, survival etc. of species in a given habitat, region or climatic zone. An important component of such models is knowledge of how well animal species can modify their bodies in response to persistent environmental signals, such as seasons or daily temperature fluctuations, and thereby to protect themselves from the debilitation by unexpected cold and heat snaps. Understanding the potential for protection requires an understanding of the fundamental mechanisms induced at the level of cell, tissue and whole body and which correlate with altered resistance to environmental stress.

Research into how animals interact with their thermal environment has progressed enormously in the past 15 years. Advances in genomic science now offers 'globalised' measurement of thermal properties of animals, meaning simultaneous assessment of all of its constituent genes and proteins. This whole-system profiling has emerged as a key tool for analysing the properties and responses of biological systems, and the outcomes have informed many different areas of biology. But the technology continues to evolve and advance. Earlier techniques have given way to new approaches that give the whole picture, with more detail, faster, and for less cost. These new techniques, mainly based on very high-throughput DNA sequencing, have recently been adapted to provide many different kinds of information.

One of these techniques allows us to quantify the number of proteins being made in tissues that are responding to sudden changes in their circumstances, such as temperature, and which improve the ability of animals to survive difficult times. Identifying the genes and proteins that respond tells us a lot about how the animal improves its life chances, when otherwise it might not survive. It also tells us which problems are caused by temperature shock and how these problems are resolved or mitigated.

Our project will apply a new technique to this well-understood environmental problem, which is how a fish survives extreme cold snaps, which can be so severe in freshwater habitats that fish are killed, sometimes in large numbers. Yet, if the fish were given a 'taste' of cool waters signalling the likely occurrance of more extreme temperatures it can prepare its body and tissues such that extreme cold isn't so damaging. So we wish to define exactly what causes debilitation and death, and how the animals protects itself from extreme, debilitating cold by preconditioning to cool. But understanding the fundamental mechanisms operating in these animals will provide information of much broader significance. The responses to cold include genes and proteins working in most, if not all, animals, which gives them an ability to respond to stressors other than cold. A good example is how a cold shock protein in fish and hibernating mammals has been shown to protect the central nervous system in mouse models from disruption caused by neurodegenerative disease.

We will extract tissues of the common carp before and after they have been cooled from a summer temperature to a winter temperature, and 'globally' measure the number and identity of thousands of new proteins created immediately after cooling. This new knowledge will point directly to responding genes and the proteins they encode. We will also focus on a particular group of genes whose proteins are already known to be highly expressed in the cold. We will test the idea that these proteins help protect the DNA and RNA of cells from structural imperfections caused by cold.

A. The commercial private sector?
Pharma might become interested in the commercial value of newly discovered systems for coping with environmental stress. This is because such systems are likely to be present in most if not all species, including farm animals and humans; it is their presentation in chill-stressed animals that makes their activity known to researchers. The problems caused by cold and warm are not dissimilar to problems faced at more normal temperatures in diseases; good examples are proteins folding diseases and prions, or problems in ensuring proper secondary structures of nuclei acids.
A very recent and possibly important example of the serendipitous biomedical application of chill research is the publication in Nature of a potential means of protecting against neurodegenerative disease through the activation of RBM3, a gene shown by us to be activated in the tissues of torpid small mammals (Nature: 15th Jan 2015). This received extensive coverage in the national press and BBC. To this extent the proposed project on chill stress can in the long term contribute to the nation's health. It is worth noting that the discovery of stress proteins originated in work on chromosomes of insects subjected to heat shock, and several decades of subsequent science now provides a very good understanding of a major element of cell biology.

B. Policy-makers
Policy makers at all levels might benefit in the longer term from a much better understanding of the potential for protection against thermal debilitation. Understanding the extent of protection, and its distribution across taxonomic grades and different geographic and climatic zones is needed to indicate the likely problems of changing climates. Understanding the extent to which protective responses work in different climatic zones (i.e. Antarctic, tropical reef etc.) is key to identifying the species that are most sensitive to climate change, both to the long-term averaged temperatures but also to the daily and weekly fluctuations that are projected to become greater as global warming progresses. This project is a discovery project that will likely form part of a major international research effort leading to these effects, and providing novel biomarkers of potential value for regulators. Thus, it will not have its full impact for some years, though we do expect that the global nature of our search for responding genes/proteins will more rapidly identify the major elements of the stress protection process.

C. The wider public
Carefully proscribing the way in which fish can be protected from chill experiences can be useful to the lay public who own amenity fish ponds or for the local ponds used in coarse fisheries throughout the UK. Thus, carp are frequently stocked in gardens (koi) or in coarse fisheries that are likely to experience extreme stress in the winter, as in December 2010 and subsequently as diseases cause some mortality due to poor condition of the fish. It is possible to define the best way of ameliorating these problems by pre-conditioning animals, and by genetic selection and stocking of resistant lines (as in the Amur strain in Asia).

D. Staff training
This project will provide high-level scientific training for two high quality postdoctoral researchers, as well as opportunities for any MSc/MRes students who wish to engage in the programme. They will experience the very latest techniques in both genomic (Hall/Cossins) and proteomic (Beynon/Eyers) research methodology, at one of 4 major sequencing hubs in the UK, core-funded by NERC and MRC, and within a well-developed and vibrant research infrastructure. They will have the opportunity for attending international meetings and to present their work.