Improving fish health and quality using naturally derived products
Submitting InstitutionKeele University
Unit of AssessmentBiological Sciences
Summary Impact TypeTechnological
Research Subject Area(s)
Biological Sciences: Genetics
Agricultural and Veterinary Sciences: Fisheries Sciences
Medical and Health Sciences: Immunology
Summary of the impact
Disease severely limits the expansion of aquaculture. Studies on the
immune control of infection have led, in association with industry, to the
promotion of disease control utilising 03b2-glucan feed supplements.
Knowledge has, via Keele
Water, informed infection control strategies used by UK fish
farmers. Studies have provided a legacy of young scientists trained by
industry and supported by European funding. Advances made have been
embraced in the education of veterinarians in Germany and fish production
in Eastern Europe. Close collaboration with government bodies and learned
societies has ensured that the work has been recognised by policy makers
within the fisheries sector.
Hoole has investigated immunological and pathological interactions
between fish and pathogens since 1987, leading to improved fish health in
aquaculture and fisheries. Since 1993, aquaculture has been the fastest
growing animal production sector. In 2010 59.9M tonnes were produced for
human consumption with an estimated value of US$ 119B. Disease severely
limits development and costs the industry US$ 3B plus US$ 3M being spent
on treatment. The IFAO has highlighted the importance of aquaculture in
providing income for an eighth of the global population and the industry
contributes to the EU Food Security agenda within the CAP and
international support programmes. Initial studies at Keele, in association
with Arme, produced the first extensive descriptions of the complex
interactions between metazoan parasites and the fish immune system. In
addition, the impact of pollution on fish and their interactions with
parasites was ascertained in association with the University of London and
Environment Agency in Wales (1995-2003). These advances were recognized
when Hoole was invited to participate 2002 in a 4 year EU Marie Curie
Research Training Network (PARITY) on the immune response of carp to
infection. The study, which took a multidisciplinary approach including
expertise from the School of Life Sciences at Keele in cancer studies
(Williams) and protein crystallography (Greenhough, Shrive), led to the
characterization of pathogen interaction at the molecular level with cell
death processes in fish, and the isolation and characterisation of innate
acute phase immune proteins. This multidisciplinary approach is still
ongoing and advances made were noted by 3 international companies involved
in the production of immunomodulators (Biorigin),
fish feed (Biomar) and the
fish ornamental trade (Tetra).
These companies collaborated with Hoole to develop a Marie Curie EU
Initial Training Network (NEMO)
along with 5 European research Institutes (2008-2013). This established
optimum protocols for the use of 03b2-glucans in the form of MacroGard®,
a by-product of the bioethanol and yeast fermentation food processes, in
the strategic improvement of fish health. Multidisciplinary approaches
entailed the formulation of 03b2-glucans into fish feed, the determination
of adverse effects on cell biology and the assessment of affects on the
carp innate immune response. Advantages of pulse feeding compared to
continual feeding were confirmed and the possible protective value of
03b2-glucan supplements on bacterial and viral diseases of carp (e.g. Aeromonas
salmonicida, KHV, SVC) was ascertained. The effects on a range of
innate immune parameters such as complement activity, cytokine gene
expression and, for the first time, C reactive protein at the gene and
protein levels was also determined. The work highlighted the cost benefits
of using naturally derived immunomodulators in fish health, allowing
farmers to reduce the application of less environmentally friendly
treatments such as antibiotics. A more recent collaboration since 2011
with Skidmore, (Life Sciences, Keele University) has led to an association
with Biorigin to establish the active ingredient of the 03b2-glucan,
potentially leading to more effective immunoprotectant. This could reduce
the amount being added to feed, thereby reducing costs of protection and
increasing product quality control and cost effectiveness of fish farming
and other animal production.
References to the research
Richards DT, Hoole D, Lewis JW, Ewens E, Arme C. (1996) In vitro
polarization of carp leucocytes in response to the blood fluke Sanguinicola
inermis Plehn, 1905 (Trematoda: Sanguinicolidae). Parasitology
112 (5): 509-513.
Penlington MC, Williams MA, Sumpter JP, Rand-Weaver M, Hoole D, Arme C.
(1997) Isolation and characterisation of mRNA encoding the salmon- and
chicken-II type gonadotrophin-releasing hormones in the teleost fish Rutilus
rutilus (Cyprinidae). J Mol Endocrinol 19 (3): 337-346.
Tharia HA, Shrive AK, Mills JD, Arme C, Williams GT, Greenhough TJ.
(2002). Complete cDNA sequence of SAP-like pentraxin from Limulus
polyphemus: implications for pentraxin evolution. J Mol Biol
316 (3): 583-597.
Carter V, Pierce R, Dufour S, Arme C, Hoole D. (2005). The tapeworm Ligula
intestinalis (Cestoda: Pseudophyllidea) inhibits LH expression and
puberty in its teleost host, Rutilus rutilus. Reproduction
130 (6): 939-945.
MacCarthy E, Burns I, Irnazarow I, Polwart A, Greenhough TJ, Shrive A,
Hoole D. (2008). Serum CRP-like protein profile in common carp Cyprinus
carpio challenged with Aeromonas hydrophila and Escherichia
coli lipopolysaccharide. Dev Comp Immunol 32: 1281-1289.
Cols-Vidal M, Hoole D, Williams GT. (2008). Characterisation of cDNA of
key genes involved in apoptosis in immune cells of common carp (Cyprinus
carpio L). Fish Shellfish Immunol 25: 494-507.
Cols-Vidal M, Williams GT, Hoole D. (2009). Characterisation of a carp
cell line for analysis of apoptosis. Dev Comp Immunol 33: 801-805.
Falco A, Cartwright JR, Wiegertjes GF, Hoole D. (2012). Molecular
characterization and expression analysis of two new c-reactive protein
genes from common carp (Cyprinus carpio). Dev Comp Immunol
Falco A, Frost P, Miest J, Pionnier N, Irnazarow I, Hoole D. (2012).
Reduced inflammatory response to Aeromonas salmonicida infection
in common carp (Cyprinus carpio L.) fed with beta-glucan
supplements. Fish Shellfish Immunol 32: 1051-1057.
Wei L, Hoole D, Sun B. (2012). Identification of apoptosis-related genes
and transcription variations in response to microcystin-LR in zebrafish
liver. Tox Ind Health 1-8.
Miest JJ, Falco A, Pionnier N, Frost P, Irnazarow I, Williams GT, Hoole
D. (2012). The influence of dietary 03b2-glucan, PAMP exposure and Aeromonas
salmonicida on apoptosis modulation in common carp (Cyprinus
carpio) Fish Shellfish Immunol 33: 846-856.
Pionnier N, Falco A, Miest JJ, Frost P, Irnazarow I, Shrive A, Hoole D.
(2013). Dietary 03b2 glucan stimulates complement and C-reactive protein
acute phase responses in common carp (Cyprinus carpio L.) during an
Aeromonas salmonicida infection. Fish Shellfish Immunol 34:
Pietretti D., Vera-Jimenez N.I., Hoole D. Wiegertjes G.F. (2013).
Oxidative burst and nitric oxide responses in carp macrphages induced by
zymosan, MacroGard and selective dectin-1 agonisys suggest recognition by
multiple pattern recognition receptors. Fish Shellfish Immunol 35:
Khalil M., Furness DN, Zholobenko V, Hoole D. (2013) Effect of tapeworm
parasitisation on cadmium toxicity in the bioindicator copepod,
Cyclops strenuous. Ecological Indicators (in press).
||£3,230 - British Council (with Pierce and Dufour,
||£17,250 - Royal Society (with Secombes, Aberdeen and Nie Pin,
||€213,200 - EU Research Training Network Grant.
||€3,078,798 - EU Initial Training Network Contract.
||£5,000 - Kurdistan Government (support for Ph.D studentship).
||£1,500 - Fisheries Society of the British Isles (support for PhD
||£7,680 - Biorigin (with Skidmore).
Details of the impact
Commercial and International Impact
(a) The research has been directly applied by industries involved in
production of immunomodulators (Biorigin)
and fish feed (Biomar,
Skretting), providing independent
verification of the importance and advantages of using MacroGard
in the improvement of fish health. Whilst unwilling to release any
sensitive commercial information, Biorigin did provide the following
statement" the results from the NEMO project have given us a better
understanding of the fish immune system in general and have contributed to
the development of new health concepts in the salmon business, where a
strong immune response is needed to prevent harmful pathogens. As an
effect of these results, Biorigin has significantly increased the sales of
MacroGard to the salmon industry". This impact has been extended globally
by the use of industrial contacts with fish production and a joint venture
between Hoole and Biorigin with ACG, the AquacultureCommunications
Group. Since MacroGard shortly loses patent protection, Biorigin are
supporting studies on the development of a new generation of
immunomodulators based on conformational changes of 03b2-glucan. The
advances made by Hoole are also being utilised by partners at Universati
Sains Malaysia in the production of snakehead and other Asian fish.
(b)The knowledge acquired by Hoole on fish diseases has been utilised
over many years by KeeleWater,
an environmental consultancy recognised by the Environment Agency to carry
out fish health checks under Section 30 of the Freshwater Fish Diseases
Act of 1975 and 1983 and "Buyer Beware Policy". Reports produced for fish
farmers and fisheries officers, and consultations, have resulted in the
implementation of management strategies and biosecurity practices which
limit the spread of disease within the fish production sector. Reports
also assist the EA to develop strategies and to reassess the threat of
individual parasite species to the UK fisheries sector.
(c) The research undertaken has also impacted on the ornamental fish
sector, an industry which is considered to be worth globally US$ 15B.
Consultations with the local Koi Carp branch of the British Koi Carp
Society have assisted ornamental fish keepers to improve their
understanding of diseases and thus implement strategies to improve fish
health and biosecurity. In addition, joint studies with Tetra
and Biomar have supported
the scientific rationale for MacroGard being placed in their feed
Impact on industrial employment skills
The EC and Industry are striving to improve the appropriate skills base
in academia, the absence of which leads to difficulties in young research
scientists initially adapting to, or following, a career in industry. In
association with three of his industrial collaborators (Tetra,
Biomar), Hoole has
established an industry-based training programme for young scientists
working in aquaculture research in academia. Workshops in industrial
research training (e.g. Fish Immunology held in the Netherlands, 11th-15th
April 2010; Protein crystallography and Molecular Modelling 15th-17th
September 2010; Carp Aquaculture held in Poland, 8th-11th May 2011;
Proteomics held in Denmark, 14-16th Nov. 2011) resulted in several young
scientists acquiring employment or sponsorship within the industrial
sector, and have established a legacy of young industry-trained research
scientists throughout the European Higher Education sector (see NEMO
Educational Impact and Raising Awareness
The research advances made by Hoole and the NEMO Consortium have been
adopted in and have modified the educational policy of several European
Higher Education and Research Institutes. The work has changed the
perception of fish disease control and, in particular, the suitability of
using prebiotics and probiotics to improve fish health. Incorporation of
the advances made into educational programmes for veterinarian courses in
Germany and specialised aquaculture workshops in Poland has impacted on
the dissemination of the knowledge base and practice within the fish
veterinary sector and the production of carp, particularly in eastern
Europe e.g. Institute
of Ichthyobiology and Aquaculture, Poland; AquaCulture
Directory (2013), FEEDINFONews
Service (2013), and the Aquaculture
Communications Group (2013).
Impact on policy makers
Studies carried out by Hoole and the NEMO consortium have attracted the
attention of the Centre for
Environment, Fisheries and Aquaculture Science. This governmental
organisation, which is aligned with DEFRA, is responsible for fish health
and associated fish policies within the UK fish production sector and UK
territorial waters. A joint meeting has been initiated to assess the
impact of the work carried out on fisheries research and future policy
strategies. This has led to continued discussions with CEFAS and the
involvement of the European Association of Fish Pathologists to
co-ordinate with Hoole to organise a conference at Keele University in
September 2014. In addition, through the Parliament Magazine's
Research-European Research & Innovation Review 2010 p26 and reports to
the European Commission through the NEMO EU project officer, the
advantages of developing natural products as immunomodulators in
aquaculture will be assessed by the Commission and will input into the
sustainability agenda within the aquaculture fisheries.
Sources to corroborate the impact
Commercial and International Impact
(a) Various publications address the use of 03b2-glucan in aquaculture
and the impact of the work of Hoole through the NEMO project (e.g. ORFFA).
(b) The value and impact of the NEMO project has been highlighted in FEEDINFO
News Service (2013); ACG
(2013) and Aquafeed
(c) Biorigin Scandinavia (independent verification of the scientific
advantages of using (03b2-glucan).
(d) Tern Fisheries Ltd. (impact of this work on fish health).
Impact on Industrial Employment Skills
(a) Environment Agency (impact of the NEMO Programme on training of EA
Educational Impact and Raising Awareness
(a) University of Veterinary Medicine Hanover (advances in education for
(b) Institute of Ichthyobiology and Aquaculture (impact of specialised
aquaculture workshops in Eastern Europe and particularly Poland).