Enhancing food safety & animal welfare via UK-US collaboration

Lead Research Organisation: University of Edinburgh
Department Name: The Roslin Institute

Abstract

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Description This US-UK partnering award started in autumn 2014. A meeting between The Roslin Institute team and collaborators at Texas Tech University, Texas A&M, Kansas State University, USDA and Zoetis was held at Zoetis HQ in Kalamazoo 8-9 October 2014 and was followed by regular video conference and E-mail exchanges. This initiated novel lines of collaboration related to an ongoing BBSRC- and Zoetis-funded project (BB/K015524/1), including the supply of research materials, staff exchanges and the joint development of a novel method to follow the fate of multiple Salmonella serovars during mixed infections (see Research Tools). This method advances the 3Rs in the development of veterinary medicines and will allow the phenotype of multiple strains of pathogens to be simultaneously evaluated in a single animal. A two-day international workshop on Shiga toxin-producing E. coli was held at Roslin in 2017, attended by collaborators from the US but also other leading STEC researchers from United Kingdom, Canada and across Europe. This highlighted recent advances in our understanding of Shiga toxin-producing E. coli and identified gaps in knowledge and future priorities. It was funded partly by this award (for US visitors; Drs Loneragan, Edrington, Bono) and partly by the Food Standards Agency of Scotland and was attended by FSA policy makers. A major area of productive collaboration was between Professor David Gally (Roslin) and Jim Bono (USDA-ARS) involving analysis of the genome sequences of E. coli and Salmonella. Prof. Bono has applied long-read sequencing to improve the assembly of E. coli O157 genomes, greatly aiding the understanding of the role of integrated prophages in the evolution of virulence of E. coli O157, as well as the evolution of E. coli O157 during outbreaks. Importantly, these teams worked closely to apply machine-learning approaches to predict the risk to humans of E. coli O157 strains found in cattle, and reported that only a subset of bovine E. coli O157 strains may pose a zoonotic risk. This approach has since been applied to other E. coli pathotypes and Salmonella enterica serovars to predict host tropism and zoonotic risk. High quality co-authored publications have arisen from these collaborations. Further exchange visits are planned in the duration of the award.
Exploitation Route Collaborative research under this award, linked to research funding from BBSRC and the Food Standards Agency, has delivered two major advances that we expect will be taken forward by others. First is a novel sequencing-based approach to simultaneously the evaluate the phenotype of multiple bacterial strains in a single animal. This has the potential to reduce the number of animals required to understand the biology of pathogens in vivo and to evaluate cross-protective efficacy of vaccines and treatments. Second is the application of machine-learning to predict the virulence and zoonotic risk of microbes. This is an important step in an era where tens of thousands of genome sequences exist for pathogens, but where the consequences of genetic variation are hard to predict. It will be evident from co-authored publications that these represent genuine collaborations between US and UK researchers and the partnering award has played an important role in initiating these studies and cementing long-term links.
Sectors Agriculture, Food and Drink,Pharmaceuticals and Medical Biotechnology

 
Description The award supported travel and research exchanges between the Roslin Institute and collaborators in the US (primarily at Texas Tech University and USDA). One major meeting of teams was held in the US in October 2014 sponsored by Zoetis linked to interests in salmonellosis in cattle (inc. via BB/015524/1). Additionally, we hosted an international workshop on Shiga toxin-producing E. coli at Roslin in 2017, attended by the key teams in the US and further supported by separate funding from the Food Standards Agency. There were regular video conferences and E-mail exchanges involving the major collaborators in the project. Impact is mostly in the form of knowledge exchange, industry interaction and training. Non-academic impact resides in the involvement of Zoetis and associated representatives of the US beef industry in the design of strategies to improve food safety. Potential for wider impact exists in the application of machine-learning approaches to microbial genomes to predict virulence and zoonotic risk (as applied by the Roslin-USDA teams to E. coli O157), for example to focus the design of control strategies and understand pathogen evolution and its consequences in a diagnostic setting. The latter was aided by the close collaboration of Professor Gally with Public Health England and the Scottish E. coli Reference Laboratory. The development of a novel method to simultaneously define the phenotype of multiple bacterial strains in a single animal also has potential for widespread adoption, for example in testing the cross-protective efficacy of vaccines or treatments. It advances the 3Rs by reducing animal use in the development of veterinary medicines.
Sector Agriculture, Food and Drink,Pharmaceuticals and Medical Biotechnology
 
Title Strategy for quantifying individual bacterial strains during mixed infections 
Description We devised a novel strategy to follow the fate of individual bacterial strains during mixed infections. Specifically, we wished to follow the fate of multiple Salmonella enterica serovars during colonisation of the bovine host. These are indistinguishable by culture, and while they can be specifically detected by serology, quantification of numbers of each serovar during mixed infection would involve analysis of many hundreds or thousands of individual colonies. We devised a method based on massively-parallel sequencing of a polymorphic allele (rpoB), whereby sequence reads can be used to identify the strain present (based on single nucleotide polymorphisms specific to each strain) and the number of sequence reads can be taken as a measure of the abundance of the cognate strain. Using this method we were able to simultaneously define the fate of 12 different S. enterica strains during infection of cattle, including as they colonised the gut over time and spread from the gut to the lymphatic system and other tissues. This 3R approach should allow phenotypes to be derived with reduced use of animals in experiments and could, for example, be used to see if vaccine-induced responses are effective in control of all the different members of a bacterial population present - in this case toward a pan-serovar cross-protective vaccine. A manuscript reporting these findings was published in late 2017 (Vohra et al). Though a direct output of BBSRC responsive-mode funding, the project was underpinned by core-strategic grants from 2012 and 2017 (e.g. via the involvement of core-funded staff in animal studies) and a BBSRC US-UK partnering award, where the ideas for following serovars based on massively-parallel sequencing of rpoB and ileS were jointly developed. 
Type Of Material Technology assay or reagent 
Year Produced 2017 
Provided To Others? Yes  
Impact Too early to say, but the method has the potential to reduce animal use in evaluating the cross-protective efficacy of vaccines or treatments as it enables many strains to be tested at once in a single animal rather than in separate groups that each receive a single strain. 
 
Description Collaboration with Kansas State University 
Organisation Kansas State University
Country United States 
Sector Academic/University 
PI Contribution Kansas State University are partners in this BBSRC US-UK Partnering Award related to Salmonella and E. coli infections in food-producing animals.
Collaborator Contribution Sharing of expertise & materials.
Impact None yet from this specific partner.
Start Year 2014
 
Description Collaboration with Texas Tech University 
Organisation Texas Tech University
Country United States 
Sector Academic/University 
PI Contribution Partner in this BBSRC US-UK Partnering Award related to Salmonella and E. coli infections in food-producing animals.
Collaborator Contribution We hosted a visiting postdoctoral research fellow (Marie Bugarel from TTU) in 2015 and provided training in methods to study the basis of Salmonella virulence (inc. mutagenesis, cell-based assays & in vivo models). Drs Bugarel and Loneragan were co-authors on our manuscript describing the use of massively-parallel sequencing of polymorphic alleles to track the fate of Salmonella enterica serovars following inoculation of cattle.
Impact A manuscript relating to a novel method to follow the fate of Salmonella enterica serovars during mixed infections was published in Applied and Environmental Microbiology in late 2017. This arose, in part, from the collaboration funded by a BBSRC US-UK partnering award (see tools), with resources from BBSRC- and Zoetis-funded project (BB/K015524/1) and core strategic grants to the Roslin Institute awarded in 2012 and 2017.
Start Year 2014
 
Description Collaboration with United States Department of Agriculture 
Organisation U.S. Department of Agriculture USDA
Country United States 
Sector Public 
PI Contribution USDA are partners in this BBSRC US-UK Partnering Award related to Salmonella and E. coli infections in food-producing animals. We have shared expertise, ideas & materials. A co-Investigator at the Roslin Institute (Professor John Hopkins) visited USDA researchers to transfer his expertise in surgical cannulation of lymphatic vessels, to allow the team to gain access to Salmonella and immune cells as they migrate from the intestines of cattle.
Collaborator Contribution Shared expertise, ideas & materials.
Impact Not at this stage.
Start Year 2014
 
Description Collaboration with Zoetis 
Organisation Zoetis
Country United States 
Sector Private 
PI Contribution The project was a BBSRC Industrial Partnership Award with Zoetis (formerly Pfizer Animal Health) to understand the role of bacterial and host factors in colonisation of the bovine lymphatic system by Salmonella. We analysed the nature and consequences of Salmonella interactions with immune cells in the gut and lymphatic system of cattle, assigned phenotypes to thousands of Salmonella genes during lymph node colonisation and analysed the relative ability of different Salmonella serotypes to enter and persist in the lymphatic system using a novel strain tracking method. The data aid the design of strategies to control Salmonella in cattle, both to benefit bovine health and reduce the impact of zoonotic infections.
Collaborator Contribution Zoetis provided $250 toward project costs and also hosted meetings of a Salmonella Research Cluster that also involved academics at Texas Tech University, Kansas State University and the US Department of Agriculture. In turn this helped to form the basis of a BBSRC US-UK Partnering Award (BB/L026732/1).
Impact See key findings.
Start Year 2012
 
Title Application of Machine Learning to predict zoonotic risk of E. coli & Salmonella. 
Description Professors Gally (Roslin) and Bono (USDA-ARS) worked collaboratively on the application of Support Vector Machine (a machine-learning tool) to genome sequences of human and bovine E. coli O157 in order to predict zoonotic risk [Lupolova N, Dallman TJ, Matthews L, Bono JL, Gally DL. 2016. Support vector machine applied to predict the zoonotic potential of E. coli O157 cattle isolates. Proc Natl Acad Sci USA. 113:11312-11317]. The approach was subsequently applied to predict the host of origin of Salmonella enterica serovars and E. coli pathotypes [Lupolova N, Dallman TJ, Holden NJ, Gally DL. 2017. Patchy promiscuity: machine learning applied to predict the host specificity of Salmonella enterica and Escherichia coli. Microb Genom. 3:e000135. 
Type Of Technology Webtool/Application 
Year Produced 2016 
Impact The application of machine learning to microbial genome sequences offers much potential to predict the virulence and zoonotic risk of emerging strains. This is reflected in publication of the first application of SVM to E. coli O157 genomes in PNAS, as well as press coverage this generated. 
 
Description Annual Roslin Institute Open Doors Day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact The annual Roslin Institute Open Doors day was held on 14 October 2017 and was attended by 491 people. It involved 81 members of staff and students and showcased a wide range of research arising from BBSRC strategic investment, including (but not limited to), food safety, influenza, genetic improvement, DNA, imaging and the ethical treatment of animals in research.
Year(s) Of Engagement Activity 2017
 
Description Feature for BBC2 Food Detectives programme 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Professor Stevens took part in a BBC2 Food Detectives programme which featured Campylobacter in chickens. He helped to design a survey of Campylobacter contamination in a sample of fresh chicken obtained from Scottish retailers and interpret the findings. This were close to Food Standards Agency findings, which were broadcast as part of an interview with Prof. Alice Roberts. The interview took place at The Roslin Institute and included a lay description of Campylobacter, the importance of chickens as a reservoir of infection and strategies by which consumers can protect themselves. It also highlighted BBSRC-funded work at Roslin to mitigate the problem based on genetic selection (this project) and vaccines (other BBSRC projects held by Prof. Stevens).
Year(s) Of Engagement Activity 2016
URL http://www.bbc.co.uk/programmes/b077rgd4
 
Description International workshop on Shiga toxin-producing Escherichia coli at The Roslin Institute 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact A two-day international workshop was held at The Roslin Institute on Shiga toxin-producing Escherichia coli (STEC), funded partly by this award (for travel of US collaborators) and partly by the Food Standards Agency of Scotland via a £2m award for collaborative research by a consortium led by Professor Gally. The workshop attracted leading academics working on E. coli O157 and other STEC from the US (Jim Bono, Guy Loneragan, Tom Edrington), Canada (Tim McAllister, Kim Stanford), Germany (Christian Menge), Belgium (Eric Cox), Sweden (Erik Eriksson, Lena-Mari Tamminen, Robert Soderlund) and the United Kingdom (Claire Jenkins, Tim Dallman, Dominic Mellor, Norval Strachan [Chief Scientific Advisor for FSA Scotland]). The workshop shared the latest advances in understanding of the biology of E. coli O157 and other STEC, including epidemiology, genomics, virulence, super-shedding and control strategies.
Year(s) Of Engagement Activity 2017
 
Description Press release on the development of a method to simultanoeusly analyse multiple Salmonella strains in animals 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Press release on work arising from this US-UK collaboration to understand the risk to food safety and animal welfare posed by Salmonella enterica serovars in cattle.
Year(s) Of Engagement Activity 2018
URL https://www.ed.ac.uk/roslin/news-events/latest-news/novel-sequencing-study-salmonella-cattle
 
Description Press release on use of machine learning to predict zoonotic risk 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Press release on use of machine-learning to predict zoonotic risk of E. coli found in cattle. This was covered on the pages of the Roslin Institute, University of Edinburgh and BBSRC. It was also described in a motion tabled at the Scottish Parliament.
Year(s) Of Engagement Activity 2016
URL http://www.bbsrc.ac.uk/news/health/2016/160920-pr-computers-learn-spot-deadly-food-poisoning-bacteri...
 
Description Public lecture entitled Confronting the Microbial Menace in Our Food'. Professor Mark Stevens 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact The inaugural lecture of Professor Mark Stevens was held on 30 October 2017 on his BBSRC-funded research to identify bacterial and host factors influencing the ability of Salmonella, Campylobacter and E. coli to colonise farm animals and cause disease. It was attended by children from local schools, members of the public, students at The Roslin Institute and wider University of Edinburgh and posted online.
Year(s) Of Engagement Activity 2017,2018
URL https://media.ed.ac.uk/media/Inaugural+lectureA+Confronting+the+microbial+menace+in+our+food/1_x5k5e...
 
Description Public lecture on microbes and antimicorbial resistance by Professor David Gally, U3A event Centre for Life, Newcastle 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Professor David Gally delivered a public lecture at the Centre for Life, Newcastle, organised by the University of the Third Age for their Microbes and Antibiotics Day on 9 October 2017. BBSRC-funded research at the Roslin Institute featured in his presentation.
Year(s) Of Engagement Activity 2017
 
Description Stand at the Royal Highland Show, including Genetic Toolbox exhibit. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Roslin Institute stand at the Royal Highland Show 22-25 June 2017. Approximately 25 Roslin Institute staff and students were involved. Exhibits of relevance to this ISP included A Genetic Toolbox exhibit, highlighting the heritable nature of traits and how these can be selected or changed.
Year(s) Of Engagement Activity 2017