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Novel biocontrol agents for insect pests from neuroendocrinology

Periodic Reporting for period 3 - nEUROSTRESSPEP (Novel biocontrol agents for insect pests from neuroendocrinology)

Periodo di rendicontazione: 2018-06-01 al 2019-05-31

For the global population, production of safe and nutritious food is a main pillar for Food Security. To achieve this, sustainable and resilient agricultural practices, with lower impact on the environment, are required. However, Food Security is critically impacted by insects, both as major pollinators and as destroyers of the world's crops; and also of animal health, as vectors of disease. Insecticides are thus used to control insect pests, which range across all production sectors, including agriculture, horticulture and forestry. Insecticide use has resulted in several problems including resistance by insects and environmental costs. Also, pests adapt and new pests emerge. There is thus a need for new, more selective (and thus 'greener') ways of controlling insect pest species whilst protecting beneficial insects. nEUROSTRESSPEP aimed to develop new small protein 'mimetics', similar in function to the insects’ own small protein hormones, which will interfere with insects’ survival ability. These may be developed as new classes of environmentally-friendly insect control agents targeted to specific groups of insects, whilst protecting beneficial insects; and which do not engender insect resistance.

nEUROSTRESSPEP’s objectives are to:
• provide a more efficient and careful husbanding of limited resources while minimizing adverse societal impact across agriculture, horticulture and forestry, together with the bio-based industries
• develop integrated mechanisms of response measures (practical solutions), ranging from prevention of entry to novel Integrated Pest Management approaches
• deliver novel, ‘green’ neuropeptide-based insect pest biocontrol tools

The programme has successfully concluded by achieving all of its objectives especially developing novel Integrated Pest management Approaches involving ‘green’ peptide-based insect pest biocontrol tools which are kind to beneficial insect species. Further development of these candidate biocontrol tools for market need and use will reduce adverse societal impact of necessary insect pest control across agriculture, horticulture and forestry. Finally, the nEUROSTRESSPEP programme will have contributed to wide-ranging impact including societal and economic outcomes.
For analysis of insect neuropeptides, we curated >6000 peptide sequences over representative 97% of insect species and developed a new, publicly-available insect neuropeptide database (DiNER).
We used cutting-edge ‘omics technologies for pest, beneficial and alien, invasive, insect species which has allowed complete and accurate prediction and identification of all bioactive neuropeptides. We also have successfully established and extended insect synthetic biology approaches for several insect species.
A range of functional studies including manipulation of neuropeptide gene expression was performed in 20 insect species for multiple neuropeptide families.
This confirmed specific neuropeptides as excellent candidates for species/order-specific insect biocontrol agents. Market analysis also validated the chosen targets in representative major pests.
>150 neuropeptide analogues were designed, synthesized and tested during the project for their ability to reduce insect survival, with assays to determine the most selective, stable and bioactive analogues.
The project has provided new bio-stable, bioavailable candidate peptide analogues which impact selectively on several pest species.
These have been tested on multiple species of non-target and beneficial insects including natural enemies and pollinators. There are no harmful effects of effective peptide analogues on multiple non-target and beneficial insect species, demonstrating a major impact for environmental sustainability and thus also achieving the project goals.
Overall, this exciting conclusion to the project has validated the conceptual framework, approaches, technologies and innovative reagents towards sustainable agriculture and horticulture.

nEUROSTRESSPEP has been disseminated widely, from policy events to exhibitions in more than 80 events at national and international levels across the EU. A range of materials for communication with key stakeholders, including a project brochure and a video content have been made and disseminated. Project outcomes have been provided for the general public in interactive format on the NSP website.
nEUROSTRESSPEP has also been represented in the popular press, at scientific conferences, trade exhibitions (e.g. InfoAgro, Almeria, Spain, attracting 40000 people) and at policy events. nEUROSTRESSPEP outcomes to date were recently communicated via an article posted on the KTN website and via KTN newsletter (6,000 subscribers), on external websites and newsletters e.g. BEIS, EuropaBio, SCI; Future of Crop Protection report by Horticulture Week (250,000+ practitioner audience). Successes and opportunity represented by the NEUROSTRESSPEP outputs, were highlighted in particular at the Stakeholder Event (Brussels, February 2019) and provided detailed coverage of the programme for a number of key industry and policy stakeholders.
Finally, nEUROSTRESSPEP has been featured as an EC ‘Success Story’ and communicated widely via EC channels.
nEUROSTRESSPEP has achieved progress beyond the State-of-the-Art in the following areas towards novel biocontrol of insect pests:
• Curation across 97% of insect species to identify order/species-specificity of neuropeptides and provision of the DiNER database for insect neuropeptides
• Use of multiple and/or combined ‘Omics approaches including transcriptomic, genomics, peptidomics and metabolomics applied to understanding neuropeptide expression and function in multiple insect species
• Established novel, fast and accurate mass spectrometry approaches for species-specific neuropeptide identification and spatial distribution
• Insect synthetic biology and genetic modification of insect pest species.
• Rational design and synthesis of >150 peptide mimetics (analogues) for efficacy, stability and bioavailability across multiple neuropeptide families
• Functional assessment of peptide analogues applied in multiple modes to many insect species
• Development of innovative cage trials for assessing impact of candidate peptides on forest pests
• Impact assessment of ‘best’ peptide candidates across multiple beneficial and non-target insect species via ring validated testing
• Discovery of innovative, selective insect biocontrol tools - peptide analogues which impact insect pests but which do not harm beneficial and/or non-target species

An assessment of the Impact of the project looking at outputs across a range of economic, societal and environmental parameters, was carried out and reported. To highlight three key examples:
- the project has delivered an IP filing and potential spinout company
- dissemination of outputs has reached a very large practitioner / end-user group including amongst the largest agricultural shows in Europe e.g. InfoAgro, Almeria
- the project has generated opportunities for career progression for many participants including a large number of female participants
nEUROSTRESSPEP at InfoAgro, Almeria, Spain, 2018
European Researchers Night, 2016
Royal Highland Show, June 2016
Insect display at UoG postgraduate Day, 2017
nEUROSTRESSPEP project at EC Agriresearch Conference, 2018