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Aquaculture meets Biomedicine: Innovation in Skeletal Health research.

Periodic Reporting for period 1 - BioMedaqu (Aquaculture meets Biomedicine: Innovation in Skeletal Health research.)

Reporting period: 2018-08-01 to 2020-07-31

The basic aim of this project is to combine the expertise in Skeletal Biology of two separate fields, aquaculture and biomedicine, to the benefit of each specialty. Skeletal deformities are intensively studied in aquaculture, skeletal pathologies are a major issue in human medicine, while small fish models provide unique tools for studies. The project includes leading academic labs and companies in aquaculture and nutrition, biomedical experts using the models zebrafish or medaka, academics and companies focusing on skeletal pathologies in humans, experts in (automatic) image analysis and in evaluation of economic outcomes. The very broad perspective ensures that the ESRs involved in the project not only acquire the expertise required for their specific activity but are also continuously exposed to the work of all ESRs. The project is contributing to the training of a new generation of researchers in skeletal Biology that are better prepared for the challenges ahead.
Training.
In addition to Each ESR's individual research programme, the ITN has delivered 2 Summer Schools (SS) aimed to deliver integrated, multidisciplinary training in skeleton anomalies in aquaculture, including research skills at anatomical, histological, and molecular levels. SS1 was dealing with fish breeding, manipulation, animal experimentation ethics, stock maintenance. SS2 was focused on recognizing, recording and analysing skeletal deformities in fish. In addition to these practical lessons, lectures were given on specific research on aquaculture and model species. Finally, each ESR presented his plans and their advancement, for discussion with the wide range of expertise within the Consortium. ESRs are exposed to the socio-economic impact of their research on aquaculture during SS2 and SS3.

Scientific Objectives:
Small model fish like medaka (Oryzias latipes) or zebrafish (Danio rerio) are increasingly used in the fields of developmental biology, physiology and pathology in vertebrates. They are pivotal in this project by linking the biomedical researchers to the aquaculture experts.
On the one hand, the project exploits data from human osteoarthritis and idiopathic juvenile osteoporosis patients to investigate the function of specific genes in the zebrafish model. Mutants were obtained for the homologs of these genes in zebrafish and are studied using specific staining methods as well as gene expression studies. Mutant human osteogenic cell lines are also used.
On the other hand, the influence of dietary components on skeletal health, probably relevant to both farmed and model fish as well as humans, is investigated.
The effect of oxidants and antioxidants is investigated on bone forming (osteoblasts) and bone degrading (osteoclasts) precursor cell survival and differentiation, as well as on the small fish models medaka and zebrafish. Potential benefits of micronutrients and probiotics used in human food supplements to the skeleton are investigated on cells, zebrafish and aquaculture species.
Extracts from marine invertebrates and microalgae have been identified that present beneficial osteogenic, anti-osteogenic and/or mineralogenic properties using several tests in transgenic zebrafish lines.
Transgenic and mutant zebrafish lines have been established to study the precise molecular mechanisms involved in repair of the notochordal sheath in zebrafish. These results may lead to better understanding of specific deformities found in the vertebral column, while the involvement of dietary phosphate levels (depletion or excess) on the occurrence of vertebral body fusions is investigated in zebrafish.
Early indicators for skeletal disease are searched for by rearing medaka or zebrafish larvae in different physical conditions using anatomical, histological, transcriptomic, proteomic and metabolomic approaches.
A software to automatically quantify bone formation and mineralisation in developing fish larvae for screening applications is developed.
Taken together, these activities illustrate innovative applications of small model species in the fields of aquaculture and medicine.
Conditions affecting skeletal health are of great concern in aquaculture, in the context of product quality (value) and animal welfare. To make fish farming more sustainable by avoiding fish oils and fish meal in their diets as well as overfeeding, nutritional factors are of particular interest.
The project investigates the effects on survival, growth and skeletal integrity of supplementing a plant ingredient diet with zinc, copper or vitamins D and K on gilthead seabream (Sparus aurata) larvae and juveniles using morphological, biochemical and gene expression studies to further understand the physiological mechanisms involved.
Meagre (Argyrosomus regius) were fed a diet supplemented with long-chain polyunsaturated fatty acids to assess their effect on larval growth, survival, fatty acid composition and skeletogenesis.
The requirement for phosphorus in the diets of Atlantic salmon (Salmo salar) is investigated with the aim to avoid overfeeding. Growth and skeletal integrity (specifically of the vertebral column) is investigated. Effects of standard handling procedures are also investigated to further ensure the well-being and health of the fish.
Gilthead seabream larvae and juveniles in different settings at commercial scales to investigate the optimal conditions for growth.
The socio-economic impact of skeletal deformities in farmed fish is assessed. The consuming and buying behaviour of EU residents towards Fishery and Aquaculture Products is analysed, while the approach of fish farmers to assess and prevent skeletal deformities in their products, as well as cost and risk estimation, will be addressed.
Taken together, all the described activities will contribute to the gain a deeper multilevel comprehension of skeletal processes in vertebrates.
The project’s interdisciplinary scope is already combining the innovative tools (mutants, gene editing, advanced imaging, etc) and the mechanistic insights obtained in biomedical research with the large data sets and analytical tools available in aquaculture research to better understand bone formation and remodelling in vertebrates as well as the mechanisms underlying fish and human skeletal diseases, bringing new knowledge that will improve quality in fish production. It brings together academic institutions, research institutes, hospitals, industrial partners and aquaculture organizations across several countries and lays the foundation for further collaboration between consortium members that balance technological and research aspects with commercial considerations.
Exploitation of the results is enhanced by inclusion of a specific individual research project studying economic impact and risk assessment aiming at creating sustainable new ventures from the research, and by active participation of several industrial partners and organizations. It will familiarize all stakeholders with the necessity to link research with the social/economic sphere.
Mobility of the researchers between aquaculture, biomedical and socio-economic fields will benefit all disciplines, thereby addressing several objectives of the Europe 2020 strategy. Novel insights will be gained about, inter alia, genetic, nutritional and environmental factors that can impact skeletal development and the impact and cost of skeletal malformation and counter-measures for society.