The available database comprises research projects in Fisheries, Aquaculture, Seafood Processing and Marine Biotechnology active in the time period 2003-2022.
BlueBio is an ERA-NET COFUND created to directly identify new and improve existing ways of bringing bio-based products and services to the market and find new ways of creating value from in the blue bioeconomy.

More information on the BlueBio project and participating funding organizations is available on the BlueBio website: www.bluebioeconomy.eu

Last Update: 2024/06/19

HepAqua
Aquaculture
Marine Biotechnology
Fish antimicrobial peptides: characterization of sea bass hepcidins and their potential therapeutic applications
Nat. Programme (supported by ESIF)
National-European
Pedro Nuno Simoes Rodrigues
prodrigu@ibmc.up.pt
IBCM-UP - University of Porto; Institute for Molecular and Cell Biology (Portugal)
NA
2013
2015
€ 185,586
https://www.fct.pt/apoios/projectos/consulta/vglobal_projecto.phtml.en?idProjecto=129390&idElemConcurso=7496
Antimicrobial peptides (AMPs) act as a first line of defence in a wide range of animal species, including fish, and constitute one of the major components of the innate immune system, which is not dependent upon recognition of distinctive molecular structures. They present not only a broad-spectrum antimicrobial activity, known to have antibacterial, antiviral, antifungal, antiparasital and even antitumoral properties, but many are also known to have other important roles in the interaction between the innate immunity and iron metabolism. Over the last decades, many different AMPs have been discovered and characterized in a variety of organisms, ranging from plants to humans. Chief among them is hepcidin, a small cysteine-rich peptide, discovered in 2000 and initially characterized as an AMP. However, since the confirmation of its function as the long sought key regulator of iron metabolism, its function as an AMP was largely disregarded. In more recent years, the interest on the antimicrobial properties of hepcidin seems to have been renovated, particularly in fish which are heavily dependent on the innate immune system for an appropriate antimicrobial response. One of the most striking differences between mammalian and fish hepcidins is that contrary to mammals, which only present 1 or 2 copies of the hepcidin gene, fish can have several genes, with many species presenting multiple functional copies. This fact raises the suggestion that fish hepcidins may have specialized in such a way that some hepcidins become mostly involved in the antimicrobial response and others in the iron metabolism regulation. The fact that fish hepcidins can be divided in two phylogenetic groups, Hamp1-type and Hamp2-type, based on the presence or absence of a specific amino-terminal sequence that might be a metal binding site, further reinforces this idea. Our team has been working on iron/immune related genes and its mechanisms of regulation in teleost fish for some years. We have shown that the European sea bass (Dicentrarchus labrax) may have up to 8 copies of the hepcidin gene. Other studies have also identified hepcidin in various fish species and shown that it is involved in both iron metabolism and the immune response. Recently some authors have started looking more closely into its antimicrobial potential, in in vitro studies. However, previous research has addressed different aspects in different species and there has not been any exhaustive study of all the different hepcidin genes in a single fish species, their involvement and interactions in the immune system and iron metabolism and their antimicrobial potential, which is what we propose for this project, making it difficult to have an integrative overview. We are now proposing to fully characterize the different hepcidin genes in sea bass, and to clarify their roles in the iron metabolism and immune response. Furthermore, we intend to discern the antimicrobial activity of hepcidin molecules both in in vitro and in vivo studies, and evaluate their therapeutic potential. There are several reasons to use fish, and in particular sea bass, as an experimental animal model. Since fish rely more heavily on their innate immune defences than mammals, they might constitute a potential rich source of antimicrobial peptides, with applicability not only for other fish but also for mammals, as demonstrated in some recent studies. With the growing importance of sea bass in European aquaculture, and the frequent economic losses caused by several diseases, it is crucial to develop new strategies to prevent, contain and treat disease outbreaks, and improve fish health. Furthermore, the team members also have extensive experience with the techniques to be used and with models of infection/iron modulation, with sea bass as well as other species. In conclusion, by dissecting the function of hepcidin in European sea bass, we aim to gain an in-depth knowledge of its antimicrobial role during bacterial infection, and to generate several peptides with potential for future therapeutic applications, not only for sea bass but also for other aquaculture species. Data obtained from this project will also contribute to the understanding of the interaction between iron metabolism and the immune system. Hepcidin is an integral part of the innate immune system, and has two major functions, playing a central role in the regulation of iron homeostasis and also acting as an antimicrobial peptide. Since its role in iron metabolism was first described in 2001,most of the subsequent studies have addressed its link to iron, with less attention paid to the understanding of the antimicrobial properties of hepcidin. The innate component of the immunological system is of crucial importance to cold-blooded animals such as teleost fish, due to their delayed adaptive immune response. Therefore, it is plausible that the role of hepcidin as an antimicrobial peptide may be of particular importance as a first line of defence during infection in fish. Both mammals and fish have hepcidin genes, with similar putative mature peptide signatures. However, contrary to their mammalian counterparts, where 1 or 2 copies of the gene seems to be the norm (single copy in humans, two copies in mice), teleost fish have a large number of hepcidin genes (as many as 16 copies have been proposed for some fish species). The fact that an unexpected elevated number of genes are found in fish genomes raises several questions that we propose to answer. Have fish hepcidins subfunctionalized, with some more involved in the mechanisms of iron regulation while others acquired a more antimicrobial role? How are they transcriptionally regulated? Is their antimicrobial function indiscriminate or specific, with different hepcidins responding to different pathogens? During the last years, hepcidin has been identified in several fish species, with several studies, including our own, showing its involvement in both iron metabolism and immune response also in fish. More recently, a renewed interest in the antimicrobial activity of hepcidin has emerged. However, there is a lack of in-depth studies that address these questions in an integrative manner. As such, the project will set out to: (1) Characterize the different hepcidins in the European sea bass (Dicentrarchus labrax); (2) Investigate the role of each of the characterized hepcidins in iron metabolism and antimicrobial response; (3) Evaluate the therapeutic potential of the different hepcidins against a range of fish and mammalian pathogens, using in vitro and in vivo assays.
Fish; Seabass; Animal welfare; Fish biology; Antimicrobials; Genetic; Bioprospecting;
Portuguese Waters (27.IXa,27.IXb)
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