Decoding the systems toxicology of Atlantic cod
Project lead: Anders Goksøyr
Institution: University of Bergen
Partners: Institute for Marine Research, NIFES, IRIS, NTNU, UiO og NMBU, Universitetet i Gøteborg, Woods Hole Oceanographic
Funding: NOK 38 mill.
As it swims along the Norwegian coastline, the cod can be a good indicator on the state of our marine environment. Now scientists want to find out how different pollutants and combinations of them affect the cod.
The cod – our new canary bird
The goal is to make a tool for monitoring the environment and to assess risk during release of potentially polluting such as from oil industry, release of sewage in harbors and industrial waste in the fjords.
The costal cod is particularly suitable for monitoring environmental pollutants as it is rather stationary and the pollutants accumulate in the liver. The scientists take out the cod liver and investigate the cod genes and how they used. Which genes are turned on or off, which proteins are encoded by these genes and what is the effect on the cells? When each cell contains about 20 000 genes and each gene can encode many proteins, the scientists will soon get an enormous amount of data to go through.
In the project biologists, toxicologists, physiologists, veterinarians, mathematicians, statisticians and bioinformaticians are working together to supervise and analyze how the cod reacts, to understand how the cod is affected by pollutants and how this knowledge can be used to monitor the environment. They also want to learn how changes in the environment and climate affect the cod stock.
The results will be useful for public agencies like The Norwegian Food Safety Authority, the Environment Agency, the Directorate of Fisheries and for the fish industry.
The experiments using living fish follow the regulations for fish welfare, but most of the experiments are and will be performed on cod liver slices.
The project is executed by a consortium led by the Department of Biology at the University of Bergen (UiB), with partners at the Department of Mathematics and Department of Informatics at UiB, The Norwegian University of Science and Technology (NTNU), University of Oslo (UiO), Norwegian University of Life Sciences (NMBU), Institute for Marine Research (IMR), National Institute of Nutrition and Seafood Research (NIFES) and International Research Institute of Stavanger (IRIS). There are also international partners in Sweden (Gothenburg), Spain (Barcelona) and USA (Woods Hole, Florida and Stanford).
Using cod to monitor the marine environment
In the project dCod 1.0: Decoding the systems toxicology of Atlantic cod scientists want to find out how the cod respond to environmental stress, either by pollutants or by climate change. This can be done by investigating liver samples and the cod genome. The project is the first to use cod as a model at this scale.
The studies are based on knowledge about the cod genome (its DNA). This genome was fist mapped in 2011 by scientists at the University of Oslo and Bergen together with international collaborators. Later, scientists in Oslo have mapped the genome of more cods. Now, these data can be used to learn how the cod responds to different environmental stresses.
The scientists are looking at genes, proteins and the metabolism of the fish. One important part of the project is to extract information from the large amounts of data and develop mathematical models of the processes that are changed in the cod.
For each tissue sample, the scientists will extract data about the transcriptome, proteome and metabolome. The transcriptome is the active parts of the genome (DNA), the genes that are actively transcribed (into messenger RNA) in a cell. The proteome is the total amount of proteins (transcribed from active genes) in a cell and their chemical modification states (usually modified after translation). One gene can give rise to several proteins, e.g. through the process of RNA splicing, and they can become chemically modified as a result of many cellular processes, such as cell signaling. The metabolome of a cell is the total amount of smaller organic molecules, metabolites, in the cell, which are formed as the result of chemical reactions catalyzed by enzymes. With each cell having about 20 000 genes and each one can give rise to proteins in many different activity states, producing more or less of different metabolites, this soon becomes Big Data. Bioinformaticians are needed to extract the interesting parts, that is, the genes, proteins and metabolites that are influenced by environmental stress.
By using topological data analysis, mathematicians can find patterns in the data and how the data is connected. This knowledge can be used to make systems biological models of the cod and how pollutants give rise to cellular responses.
The results can provide answers to how different environmental stressors affect the inner life of the cod, so that scientists can make models of how environmental changes affect the population size and develop tools for risk assessment and for monitoring the environment.
Cod cells from many sources
Pollution is not necessarily lethal or directly damaging to the fish, but if it affects the growth or its reproduction; even low doses of pollution will have consequences on the stock and in that way affect the fisheries.
Scientists get their «raw materials» from four sources:
They catch cod that lives in areas of high pollution and sample tissue such as liver.
They grow slices of liver from cod in the lab, a technique that is also used in DigiSal, a different project in the Centre. Each slice can be exposed to pollutants to investigate the effect on the cells. The advantage is that the experiments can be performed under controlled conditions and that fewer animals are needed.
They keep live cods in cages at different locations in the sea where they are investigating the environment. One such experiment has been performed already, at Kollevåg outside Bergen, to check if environmental pollutants are leaking from an old dump site. The cods live in their cages for four to six weeks before sacrificed and sampled.
They use aquaria containing living fish that is exposed to mixtures of environmental pollutants to see how the fish behaves.
The project, which is led from the University of Bergen, bringings together scientists from a range of different disciplines: Biologists, toxicologists, physiologists, mathematicians, statisticians and bioinformaticians. This is the first time an environmental research project on fish has a consortium of such wide spread disciplinary composition.
All scientists in the project meet physically a couple of times every year. The majority of project employees are located in Bergen, and there the scientists meet every second week, whereas others can join by Skype.
It has always been important to meet and talk together, to discuss scientific problems from the different angles and using their own language. Slowly, a common language and understanding will be developed across the disciplinary boundaries. For most of the project participants it is new for biologists and mathematicians to work together. The interaction is particularly important for PhDs and postdocs that work full time in the project.
Responsible Research and Innovation (RRI)
A pervading philosophy in the project is that the science should be beneficial for the society. One example is the tools that will be developed for monitoring the marine ecosystem to provide the environment agency with better models for risk assessing the level of pollution. In addition, the dCod 1.0 scientists will engage in dialogue with stake holders like the Institute for Marine Research, Environmental Agency, Directorate of Fisheries, stake holders in fisheries and the society in general.
The project follows the 3R-prnciples of animal experiments (reduction, refinement, replacement), that is, to reduce the number of fishes to be used, to ensure minimal suffering and to get best use of the data from the experiments. One important experimental design to reduce the number of fishes used is to use liver slices.
The project will develop tools for environmental monitoring in a new way, using new software tools and modeling methods. The results will be important for biological research, for risk assessing environmental stress and to understand how it affects the fish stock. The goal is to commercialize the some of the tools developed in the project.
Two new master's of science from the dCod 1.0 project Oct. 4, 2021 11:32 AM