13TSB_ACT Putting the Ecology into Efficacy: a new paradigm for pesticide discovery

Chemical crop protection remains central to meeting the challenges of food security, changes in geographical distribution of pests, and emergence of pest resistance. Discovery of new pesticidal products adopts a screening approach with largely empirical optimisation once candidate molecules are identified. This project will investigate a new paradigm in pesticide discovery/optimisation. Therein, the development process will be driven by detailed understanding of the ecology of target species bedded within a modelling framework to identify optimal molecular properties, formulation, timing and placement of the crop protection product.

Chemical crop protection remains central to meeting the challenges of food security, changes in geographical distribution of pests, and emergence of pest resistance. Discovery of new pesticidal products adopts a screening approach with largely empirical optimisation once candidate molecules are identified. This project will investigate a new paradigm in pesticide discovery/optimisation. Therein, the development process will be driven by detailed understanding of the ecology of target species bedded within a modelling framework to identify optimal molecular properties, formulation, timing and placement of the crop protection product.

Syngenta will apply the outputs to gain a greater understanding of how to control pest populations in different crops, soils and weather conditions and thereby to develop appropriate new molecules that are more likely to succeed in the field. We will specifically develop the models for two of the largest markets for crop protection products: the potato cyst nematode (65% of potato land infested & 50 Mio GBP loss per year in the UK alone [Scottish Crop Research Institute]) and the western corn rootworm (yield loss >800 Mio USD per year & money spent for control > 200 Mio USD per year in the US alone). The recent introduction and spread of the western corn rootworm in Europe means this market is expanding.

This early stage feasibility study will deliver model prototypes parameterised for the western corn rootworm and potato cyst nematodes. These tools will be directly applied within Syngenta's research and development program to improve the search for new active ingredient molecules for the two pests selected for this feasibility study. During this "on-the-job testing" we will demonstrate how to use the modelling framework for (i) the design and selection of active ingredient molecules, and (ii) the derivation of optimal application rates and patterns. This will allow us to communicate the strategic value of the modelling framework to drive active ingredient research across the business. The demonstration phase will include combinations of active ingredients to use different toxicity profiles most effectively together (e.g. "stun, knock-down, suppression"). Furthermore, we will explore and present ideas for future development and applications of our modelling framework.

There is a long track record of the York team working successfully in partnership with Syngenta across a range of projects. The relationship started in the mid-1990s when the PI was employed by Cranfield University, eventually establishing Cranfield Centre for EcoChemistry. Specific mechanisms to maximise dissemination of the research within Syngenta include the integrated programme of work with matching of scientific expertise across the two organisations; resources requested to allow Agatz (PDRA) to work at Syngenta for designated periods; and a cash allocation from Syngenta to create a user-friendly interface for the model to facilitate uptake across the business.

The project team have extensive experience of the translation of research into impact. The PI was a member of the Defra Advisory Committee on Pesticides for six years (2007-2012) and he Chairs the International Conference on Pesticide Behaviour in Soils, Water and Air which takes place in York every four years (www.york.ac.uk/environment/pesticides). Several of his research projects have led to direct uptake into risk assessment practice at European and national level (e.g. http://www.york.ac.uk/environment/pesticides/#tab-2). The PI has contributed on behalf of the European Commission, European Food Safety Authority and Defra to advise on developments in chemical risk assessment as well as advising multinational companies, the European Crop Protection Association and the European Life Sciences Institute. TSB-funded research to develop the PESTER model (100874) involved the lead scientists from York (Brown) and Syngenta (Sweeney); this project was successfully completed in autumn 2013 and the model is in the preliminary stages of incorporation into risk assessment procedures, facilitated by active promotion through a range of international and national fora. Syngenta funded work on TKTD modelling in fish during 2011 and 2012 involved Ashauer (York) and Thorbek (Syngenta) and the resulting TKTD model has been submitted as part of the regulatory environmental risk assessment for a new compound at the end of 2012.