The interplay of rodent behaviour and semiochemistry: from scientific principles to control strategies

Lead Research Organisation: University of Liverpool
Department Name: Institute of Integrative Biology

Abstract

Commensal rodents are major pests of humankind. They have profoundly negative impacts through crop and food damage, carry human and animal diseases, cause allergy and asthma, and damage to the built environment. The costs of rodent infestations are difficult to quantify, but worldwide this runs to many billions of pounds. For example, food loss and damage caused by rats in the United States alone was estimated as $19 billion in 2000. In rice-growing regions, rodents cause annual pre-harvest losses of 5-17%: models suggest that a 5% reduction in rodent losses to the cereal harvest in undernourished countries could feed one third of all undernourished people worldwide. In the built environment, cable damage presents a significant risk of fire and electrocution, with costs of damage to infrastructure in the UK estimated around £200 million (2004). Rodents are also important in the spread of a large number of livestock and human diseases, including foodborne diseases; and contribute a significant source of allergens in residential areas that correlate with asthmatic symptoms. Current control strategies rely heavily on widespread and rather indiscriminate use of rodenticides, although the need for more integrated pest management approaches is increasingly recognized. Anticoagulant rodenticides (at least 90% of those used within Europe) are coming under increasing regulatory pressures due to persistence in the environment and negative impact on non-target species. There are growing problems of rodenticide resistance and public concern about humaneness. Thus, there are urgent needs to develop new control approaches, to significantly increase the efficiency and targeting of conventional approaches, and to develop alternative non-lethal approaches that increase the effectiveness, sustainability and humaneness of rodent control. Our goal is to develop new tools and strategies for rodent pest control, based on the use of scent signals (semiochemicals) to manipulate roent behaviour. Rodents are critically dependent on scent cues for social communication, for the coordination of reproduction and reproductive investment, for navigation around the habitat and for predator avoidance. This provides the opportunity to manipulate such signals for control purposes, as has been developed very successfully for insect pest control. However, the complexity and individual variability of mammalian scent cues, combined with flexible and adaptive responses, demands a subtle integrated and interdisciplinary approach to understand the key components of signal and response and establish the potential for manipulation from a practical perspective. To achieve this, we bring together world-leading experts in wild rodent behaviour and chemical communication, the chemistry of volatile and protein pheromones, and the deployment of semiochemical-mediated strategies for pest control. The programme will focus on house mice and brown rats as the two most important rodent pests in the UK and worldwide, and will generate approaches that can also be translated to other rodent pest species. Our specific objectives are to * build a full understanding of the scent components that stimulate behaviours that have considerable potential for pest control; * understand scent deposits and signals and how these change with scent age, so that we can mimic them for pest control and use them to monitor infestations; * explore how to exploit the flexible learning that is typical of mammalian responses to scents; * test the ability of synthetic signals to manipulate key aspects of behaviour and reproduction in semi-natural environments. A stakeholder group comprising representatives of the pest control, environmental health and food industries, regulatory bodies, and scientific expertise of rodent pests in developing countries will ensure appropriate focus and provide pathways to the industries involved for subsequent deployment.

Technical Summary

Our goal is to develop new tools and strategies for rodent pest control, based on the use of scent signals (semiochemicals) to manipulate rodent behaviour. Rodents are critically dependent on scent communication to coordinate reproductive behaviour and investment, competitive and cooperative interactions with conspecifics, habitat navigation and avoidance of predation. Three types of signal, involving volatile and involatile components, have strong potential for exploitation: pheromones used to recognize safe sites and trails; pheromones involved in sexual attraction and competitive signaling; and predator scents that stimulate avoidance. These signals induce strong innate responses combined with learning that underpins the typical flexible and adaptive use of semiochemicals by mammals. We will build an integrated understanding of the scent components and responses that could be used to improve the effectiveness and targeting of conventional control methods, or to provide new non-rodenticide approaches. This interdisciplinary programme involves specialists in rodent behaviour and scent communication, chemical ecology and biochemistry of volatile and protein pheromones and their carriers. We will combine gas and liquid chromatography, mass spectrometry, NMR, chemical/protein synthesis and scent manipulation, integrated with appropriate behavioural bioassays, to identify and characterise key constituents of both signal and response, and define the dynamics between volatile components and proteins that bind them. Once we have identified and synthesized stimuli that have key effects under laboratory conditions, we will test their ability to replicate or disrupt normal behaviour in semi-natural environments where responses can be fully monitored. A Stakeholder group of relevant national / international industry representatives, external organizations and individual experts will provide guidance to maintain a realistic focus and provide a clear pathway to exploitation.

Planned Impact

The scientific outputs from this project will have significant benefits in terms of food security, human and livestock health, the economic impact of infrastructure damage, and the potential for reduced ecological and other damage to non-target species. The potential benefits have both a national and an international perspective as this proposal focuses on rodent species that are worldwide pests and addresses fundamental aspects of the behaviour of rodents and their use of information in scents. The importance of this proposal is highlighted by the level of end-user support (see attached letters of support). Improved food security, gained through better rodent control will have major benefits for: * food producers and retailers, by reducing major losses at all levels of production, storage and distribution of a wide variety of foods; reduced contamination events and the negative impact on consumer perception of brand; * reduction of food costs to the general public and increased food available to undernourished people particularly in developing countries; given the predicted substantial increase in food demand over the next 50 years, it is essential to find more effective ways to reduce pre and post harvest losses to rodents; * reduction in the spread of food-borne diseases through rodent vectors such as Salmonella and Campylobacter, benefiting livestock farmers, the general public, the health services, the catering industry and reduced sickness costs to industry. A reduction in other rodent-borne diseases, such as leptospirosis, lymphocytic chorio-meningitis, pasteurellosis, cryptosporidiosis, toxoplasmosis and swine dysentery, and reduction in rodent allergens correlated with asthma, will benefit: * human health (public, health service and industry benefits); * livestock producers; * environmental health services and hospitals; * the welfare of livestock and other animals including companion, laboratory and zoo animals at risk of rodent-borne infections. Prevention of damage to materials and infrastructure will have major benefits for: * private industry and public services responsible for maintaining infrastructure damaged by rodents; * industry and the general public through reduction in rodent damage, for example to communications and electric cabling, machinery and reduced risk of fires and electrocution; * industry through reduction in damage and spoilage to insulation and packaging materials. Improved targeting and efficiency of conventional rodenticides and traps through the application of scent signals, or the use of information in natural scent deposits to monitor infestations, will provide: * new products and tools for manufacturers, distributors and service companies in the pest control industry or public services; * reduction in the amount and distribution of rodenticide used, reducing the exposure of non-target species such as predators or other non-pest animals that take toxic baits, of increasing concern to regulators and society; * improved efficiency of control at low population densities, reducing the number of individuals killed by rodenticides with commensurate reduction in the welfare costs of rodent control and the exposure of predators and scavengers to toxic prey. The development of additional non-lethal approaches will benefit: * regulators requiring a reduction in the use of rodenticides that are highly persistent in the environment; * the pest control industry and customers seeking alternatives to the use of rodenticides; * industry, environmental health services and the general public, particularly if new European regulation limits the conventional use of rodenticides to control rodents; * societal concerns about the humaneness of rodenticides as the main means of rodent control.
 
Description A mid-term review of this grant was submitted to BBSRC in January 2015, when some of the objectives were altered. Findings are commercially sensitive so will not be detailed here.
Exploitation Route Manuscripts reporting major findings are still in preparation.
Sectors Agriculture, Food and Drink,Environment,Government, Democracy and Justice

 
Description As we are still conducting the project and outputs are restricted due to the need for IP protection, impacts from the work largely concern alerting stakeholders to the potential of our project, and stimulating interest from industry on ways they could consider alternative approaches to rodent control.
Sector Agriculture, Food and Drink,Environment
Impact Types Societal,Economic

 
Description ALERT13
Amount £213,000 (GBP)
Funding ID BB/L014793/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2014 
End 12/2019
 
Description ALERT14
Amount £480,000 (GBP)
Funding ID BB/M012557/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2015 
End 12/2020
 
Description BBSRC DTP
Amount £120,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2013 
End 09/2017
 
Description CNRS subcontractors
Amount £14,608 (GBP)
Organisation National Center for Scientific Research (Centre National de la Recherche Scientifique CNRS) 
Sector Public
Country France
Start 09/2015 
End 08/2016
 
Description Catalyst Fund
Amount £45,540 (GBP)
Funding ID 16-VUW-011-CSG 
Organisation Royal Society of New Zealand 
Sector Learned Society
Country New Zealand
Start 05/2017 
End 09/2018
 
Description Industry
Amount £20,040 (GBP)
Organisation Rabbitwise-plus 
Sector Private
Country Unknown
Start 07/2015 
End 04/2016
 
Description Sparking Impact Award
Amount £10,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 06/2013 
End 05/2014
 
Description Darcin neuroscience 
Organisation Columbia University Medical Center
Department Department of Neuroscience
Country United States 
Sector Academic/University 
PI Contribution Provision of expertise to experimental design, analysis, interpretation, provision of materials required for research, manuscript preparation.
Collaborator Contribution Gained funding, expertise in experimental design, conducted practical research, analysis and interpretation, provided materials required for research, manuscript preparation.
Impact Neuroscience, animal behaviour, protein biochemistry. A manuscript originally submitted to Nature is currently being revised for invited resubmission.
Start Year 2013
 
Description MS collaboration (Waters) 
Organisation Waters Corporation
Department Micromass UK Ltd
Country United Kingdom 
Sector Private 
PI Contribution Development of new applications for ion sources Collaboration on publications
Collaborator Contribution Access to advanced technology Support for CASE studentship applicationd
Impact Joint publications CASE students
Start Year 2010
 
Description MUP genetic polymorphism 
Organisation University of California, Berkeley
Department Museum of Vertebrate Zoology
Country United States 
Sector Academic/University 
PI Contribution Experimental design, MUP phenotyping, data analysis and interpretation, drafting of paper for publication
Collaborator Contribution Experimental design, Mup genome and transcription analysis, data analysis and interpretation, drafting of paper for publication
Impact Published primary paper in PLOS Genetics (see url above). Further work in preparation for publication. Computational genomics, proteomics, animal behaviour, evolutionary biology
Start Year 2013
 
Description Montpellier 
Organisation University of Montpellier
Department Institute of Evolutionary Sciences (ISEM)
Country France 
Sector Academic/University 
PI Contribution Discussion of theory, analysis of scent components, preparation of materials for testing, preparation of publications and other outputs
Collaborator Contribution Discussion of theory, collection of scents for analysis, testing materials, preparation of publications and other outputs
Impact First primary publication just accepted in Scientific Reports, still in press. Animal behaviour and protein biochemistry
Start Year 2015
 
Description New Zealand 
Organisation Victoria University of Wellington
Department Geography, Environment & Earth Sciences
Country New Zealand 
Sector Academic/University 
PI Contribution Molecular characterisation of scents from pest species
Collaborator Contribution Collection of scents for analysis and field testing of response to scents and scent components
Impact Funding from Royal Society of New Zealand
Start Year 2015
 
Description Sexual pheromones 
Organisation University of Valencia
Country Spain 
Sector Academic/University 
PI Contribution We have provided essential materials for testing, advice on the behavioural and molecular design of experiments, molecular analysis of samples, and intellectual contribution to the analysis and interpretation of results and to manuscripts
Collaborator Contribution Our collaborators have taken the lead role in designing experiments for our joint work, carrying out experiments and drafting manuscripts and other presentations
Impact Multi-disciplinary - neuroscience, animal behaviour, protein analyses and synthesis Martín-Sanchez A, McLean L, Beynon RJ, Hurst JL, Ayala G, Lanuza E, & Martinez-Garcia F (2014) From sexual attraction to maternal aggression: When pheromones change their behavioural significance. Hormones & Behavior Lanuza E, Martín-Sánchez A, Marco-Manclús P, Cádiz-Moretti B, Fortes-Marco L, Hernández-Martínez A, McLean L, Beynon RJ, Hurst JL, and Martínez-García F (2014) Sex pheromones are not always attractive: changes induced by learning and illness in mice. Animal Behaviour
Start Year 2012
 
Description AWRN inaugural meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Networking event for researchers, practitioners and organisations involved in animal welfare research
Year(s) Of Engagement Activity 2016
 
Description Australia National Arts & Literary Radio 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact An audio podcast was provided for a themed episode of the Books and Arts radio program for the Australian Broadcasting Corporation. The editor of the program was delighted with it as a particularly unusual contribution.
Year(s) Of Engagement Activity 2017
 
Description BSPR Nominated Lecturer 2016-2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact BSPR Lecture "The proteomics of sex" delivered to Duke University, CALTEH, Dundee, and the London Biol Sci Ms group
Year(s) Of Engagement Activity 2016,2017
 
Description Cafe Scientifique 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact 30 members of the general public attended a talk given in a central location in the city, which sparked much discussion and questions afterwards. The outcome will have been increased education of those attending in an area of science very new to them.
Year(s) Of Engagement Activity 2015
 
Description Cafe Scientifique Liverpool 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Talk, with Prof Jn eHurst, about how proteins are made, and how their shape dictates function.
Year(s) Of Engagement Activity 2015
 
Description Cafe Scientifique, Glasgow 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact It's all about the actors, darling!

I had the pleasure of delivering a Café Scientifique discussion in Glasgow in May. This is a very long running forum, and has been run by Professor Mandy McLean and her colleagues since 2004 (Prof McLean received an MBE in 2010 for her public engagement activities - who says outreach doesn't get recognised?).

The title of my talk was 'The cell, a factory run by actors'. The format was a 20minute introduction (no slides, no projector -a refreshing change that would do us all good from time to time - I prepared so much better without the crutch of slides to prop me up) - I introduced myself as a protein chemist, discussed proteins I had discovered in my career, and the fun to be had in naming them (the darcin story always gets a good reception) and then explained how 'proteins' (the term coined by Berzelius in 1838 from the Greek p??te??? ('proteios'), meaning 'of the first rank') had been embedded in literature and arts (think Kurt Vonnegut in 'Cat's Cradle and 'Space Oddity', jus for starters) but I also quoted one of my favourite books, 'For the Love of Enzymes: The Odyssey of a Biochemist' in which he said, paraphrasing "DNA and RNA provide the script, but proteins are the actors".

I then directed the audience (between 30 and 40 people) to the first question on my short pub quiz. They were challenged to calculate how many possible proteins of 300 amino acids there could be (prefaced by a chat about polymers, building blocks and the significance of precise order). The audience did it! As Douglas Adams might have said, the answer is 'a hugely, mindbogglingly big number' and far exceeds the number of atoms in the Universe. We then addressed the logical outcome, that the evolution of life on this planet very quickly got locked into a tiny little corner of the hyperdimensional space of 'all possible proteins', and that 'out there' in that hyperdimensional space, there were perfect antimicrobials, cures for all diseases, proteins that could support green chemistry, proteins that were as clear and sparkled like diamonds. If only we knew how to get to them (and synthetic biology is not the answer).

The second part of my short introduction talked about complexity. We discussed the size of a yeast cell (100 cells end to end in one millimetre) and the complexity of this cell compared to an Airbus A3800 - the yeast cell has about 60 million molecules, the A380 has only 4 million parts, which led to the final part of my introduction - how do you manage this complexity, controlling the number of each protein a cell needs, and changing those numbers to respond to demand (stimuli) Is the cell a 'just in time' manufacturer, a 'just in case' manufacturer or a 'rapid recycler'? 

The following discussion (90minutes, with a very welcome bar break in the middle) was fabulous. This was a switched on audience - we ranged from pre-biotic evolution through panspermy to insulin secretion as a 'just in time' process. Inevitably, the darcin story took us back to a detailed discussion about the sex life of the mouse, a change to amuse, inform and extol the value of multidisciplinary collaboration with Jane Hurst and colleagues in Leahurst as behavioural ecologists par excellence. Inevitably we addressed the issue of how we do this work and the need for protein chemists to be 'technologically overstimulated' -especially for the big projects like our recently published study that quantified the number, in copies per cell, of over 2,000 yeast proteins.

I loved every minute of it. The QandA session was chaired by Vanessa Collingridge, broadcaster and writer, who was terrific.

To any of my colleagues who are thinking about this, my advice is 'go for it!'. Leave the slides behind, don't overplay the minutiae, and enjoy two hours in the company of an interested and intelligent audience who challenge you to jump around in your favourite playground - the subject that brings you in to work every morning with a bounce!

Rob
Year(s) Of Engagement Activity 2016
 
Description Environment Agency consultation 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Discussions over environmental health issues concerning rodent control, helped to shape our understanding of practical issues concerning the likely applications of our research
Year(s) Of Engagement Activity 2014
 
Description Environmental Agency non-target species 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Discussion of problems encountered with non-target species, led us to expand our approach to improved targeting of control measures
Year(s) Of Engagement Activity 2014
 
Description In Our Time Pheromones 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Invited guest on radio programme 'In Our Time' on BBC Radio 4 to discuss pheromones and their applications in society, available freely as a podcast on the Radio 4 website. Led to a number of email enquiries and contacts to share further information from general public.
Year(s) Of Engagement Activity 2019
URL https://www.bbc.co.uk/programmes/m0002mdl
 
Description Innovate UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Industry/Business
Results and Impact Advertisement of breadth of research activity at the University of Liverpool in Food Security
Year(s) Of Engagement Activity 2014
 
Description Meet the Scientists day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Poster and activities to engage children and other members of the general public to understand the importance and need for the research.
Year(s) Of Engagement Activity 2015
 
Description Merseyside & Cheshire rodent operative training 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Talk sparked many questions and much discussion

Offers were made to allow members of our research team to experience day-to-day problems of professional operatives
Year(s) Of Engagement Activity 2012
 
Description Ness Gardens Science Fair 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Activities run for children attending a local Science Fair to help children and parents understand the issues involved in rodent pest control that we are addressing. This sparked much hilarity and sticky fingers as well as increased interest in the subject.
Year(s) Of Engagement Activity 2016
 
Description New Zealand Superlures 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk sparked many questions and discussion at a workshop

Workshop led to much discussion about new approaches that could be taken in New Zealand to help control invasive rodents
Year(s) Of Engagement Activity 2013
 
Description PPC Live 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Platform presentation at annual meeting of the British Pest Control Association which sparked questions and discussion and increased interest in the approaches we are developing.
Year(s) Of Engagement Activity 2016
 
Description Pest Magazine 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact An article on our research project was published in Pest Magazine, the UK's only independent magazine for pest management professionals which is also subscribed to by an international readership. This updated professional practitioners and others in the pest control industry about the progress of our project.
Year(s) Of Engagement Activity 2016
 
Description PestTech 2014 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Members of the team interacted with pest control industry representatives to find out about current practice

Changes in understanding of current practice and latest development among the scientific team. Offers to publicise the research further to the industry.
Year(s) Of Engagement Activity 2014
 
Description PestTech presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Talk sparked considerable interest among the pest control industry together with offers to promote further publicity and provide access to study sites

Heightened interest among pest control industry of new approaches to improve rodent control, led to many additional invitations to talk with stakeholders and sharing of useful information
Year(s) Of Engagement Activity 2012
 
Description STEM 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Built a strong relationship with Winstanley College, leading to joint grants from RSC and RSoc.
Year(s) Of Engagement Activity 2014,2015,2016
 
Description Stakeholder meeting 2013 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Interaction with a broad range of relevant industry stakeholders for much discussion about the research and practical applications

Requests for further information and slides for representatives to present to their companies
Year(s) Of Engagement Activity 2013
 
Description Syngenta Rodent Workshop 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk sparked many questions and much discussion

Contacts with relevant regulators and industry representatives from North America, and additional information about specific issues that differ from UK
Year(s) Of Engagement Activity 2013