Exploiting eIF4E-based and associated broad-spectrum recessive resistance to potyviruses in dicots and monocots.

Lead Research Organisation: University of Warwick
Department Name: Warwick HRI

Abstract

The project is a collaboration between Warwick HRI working on the dicotyledonous brassica plants and Rothamsted Research working on the monocotyledonous plants barley. The main aim is to: exploit sources of recessive eIF4E-based resistance to potyviruses in these plants. The involvement of the plant gene eIF4E in the life-cycle of viruses was first discovered in experiments on Turnip mosaic virus (TuMV, a potyvirus) and Arabidopsis. Subsequently it was found that the genes eIF4E or its isoform (eIF(iso)4E) are responsible for natural resistance to potyviruses in a range of crop types. The basis of the resistance is that potyviruses require one of these genes in order to complete their life-cycle. It is known that plants with specific alterations in these genes that affect the binding between the plant protein it codes and a viral protein (VPg) are resistant to infection. We have shown that eIF4E is associated with resistance to potyviruses in brassica and barley. The resistances described so far in other plant types involving eIF4E alone are not effective against all strains of the particular potyvirus. However, we have shown that in a brassica, eIF4E in combination with another gene (retr01), confers resistance against all strains of the potyvirus (TuMV). Other genes are involved in the interaction between the viral VPg protein and eIF4E, these include a the very similar gene eIF(iso)4E and other associated genes (eIF4G, eIF4A and isoforms of these). By studying the natural variation in the eIF4E and eIF(iso)4E genes from resistant and susceptible Brassica rapa and barley lines we aim to find new sources of resistance and understand the mechanism of the resistance. We will screen a collection of plants representing 95% of the genetic variation available within the brassica species and a barley diversity panel consisting of up to 800 landraces. Those plants that differ within the eIF4E gene will be tested with informative isolates of the potyviruses to check for resistance/susceptibility. Any eIF4E or eIF(iso)4E variants conferring resistance will be sequenced. This will be supported by looking at plants that have been mutated with chemicals to identify other novel changes in eIF4E and eIF(iso)4E alleles. Lines with such changes will be tested for resistance to a panel of BaMMV and BaYMV isolates. The aim is to identify forms of eIF4E that confer resistance that is durable to all (or most) virus isolates. Using the crystal structures available for eIF4E a model will be generated for eIF4E from barley and B. rapa. Natural and chemically-induced changes in the building blocks (amino acids) of the eIF4E associated with virus resistance in barley and B. rapa will be mapped on the 3D model of the normal eIF4E proteins. The effect of the changes on the potential ability of barley and B. rapa eIF4E to bind to the viral VPg protein will then be investigated. The outcome of this work will be the prediction of superior resistance genes of barley and B. rapa eIF4E for deployment in breeding. A gene retr01 which in combination with eIF4E confers the broad-spectrum resistance to TuMV in B. rapa will be fine mapped to identify the gene's position in the plant genome. The sequence of the gene will be used to search databases to predict its function, understand the mechanism of the broad-spectrum resistance and how retr01 might interact with eIF4E. Based on the best sources of virus resistance in brassicas and barley, changes associated with the genes conferring resistance will be used to design assays which can be used by breeders to incorporate the resistances into their elite breeding stocks by normal breeding methods (crossing). The project will provide an understanding of the scientific basis of the broad-spectrum resistance. Once the mechanism is understood it should be possible to deploy such resistance in a wide range of economically important crop species.

Technical Summary

The Potyviridae is the largest family of plant viruses in the world and cause some of the most important virus diseases of crops in the world. Plant resistance to viruses is the only reliable and sustainable means of control. Potyviruses seem to require the eukaryotic translation initiation factor 4E (eIF4E plant gene) for successful multiplication in the host. Incompatibility between variants of eIF4E genes and the potyvirus VPg has been found to be the basis of natural resistance to potyviruses in several species. eIF4E-based resistance is frequently strain-specific. This project aims to look for natural allelic variation in eIF4Ee within brassica and barley. Chemically induced allelic variants of eIF4E identified using barley TILLING populations currently available will increase the likelihood of finding novel variants capable of conferring resistance to potyviruses. Using these approaches and through modelling the likely effect of the different alleles on the known binding sites within the protein from both monocots and dicots we aim to identify and predict those likely to confer resistance to resistance breaking strains of the potyviruses. Other genes have been identified that have a role in the eukaryotic initiation complex (EIC) including eIF(iso)4E which has also been shown to be capable of conferring resistance. Allelic variation and possible associated resistance in this gene will also be investigated. In B. rapa we have already mapped a second gene (retr01) which with eIF4Ee confers broad-spectrum resistance to TuMV. This presents the opportunity to develop more durable resistance. By identifying this gene we will be able to determine if it is involved in the EIC and whether it interacts with eIF4Ee to confer broad-spectrum resistance. Discovery of the gene/s underlying broad-spectrum potyvirus resistance associated with eIF4E and markers for these provides the exciting possibility of developing durable potyvirus resistance in a wide range of crops.

Publications

10 25 50

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Michelmore R (2017) Foundational and Translational Research Opportunities to Improve Plant Health. in Molecular plant-microbe interactions : MPMI

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Qian W (2013) Mapping and candidate-gene screening of the novel Turnip mosaic virus resistance gene retr02 in Chinese cabbage (Brassica rapa L.). in TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik

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Shopan J (2017) Eukaryotic translation initiation factor 2B-beta (eIF2Bß), a new class of plant virus resistance gene. in The Plant journal : for cell and molecular biology

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Sánchez F (2015) Viral Strain-Specific Differential Alterations in Arabidopsis Developmental Patterns. in Molecular plant-microbe interactions : MPMI

 
Description BBSRC-funded researchers have described a mechanism conferring resistance in brassica plants to Turnip mosaic virus, a discovery which it is hoped will lead to durable resistance being introduced in to food crops.

The University of Warwick, Chinese Academy of Agricultural Sciences and Syngenta Seeds team report their finding in The Plant Journal.

Turnip mosaic virus (TuMV) can infect all kinds of plants, including oilseed rape, peas, cabbages, broccoli, Brussels sprouts, turnips, radish and cauliflower; it causes significant damage and losses to crops. TuMV is a member of the largest taxonomic group of plant viruses causing major diseases in most crop plants and hence the discovery has tremendous generic relevance.
In their paper the researchers have unravelled the mechanism behind a novel broad-spectrum, recessive and potentially durable resistance to the virus and identified the gene involved.

The resistance, which arises from a particular form of a gene called eIF4E, has been shown to be effective against different strains of TuMV from across the world.

The University of Warwick has patented the generic resistance mechanism; Syngenta Seeds have purchased the generic patent and are currently introducing the resistance gene into commercial varieties of brassicas via a breeding programme. The breeding programme has been speeded up dramatically by the identification of the gene at Warwick, this has allowed Syngenta to use marker-assisted selection for the gene. Pre-commercial field trials are planned for 2016.
Lead investigator Dr John Walsh, from the University of Warwick, said: "This is the culmination of careful and detailed research built on in depth knowledge of the virus and its interactions with brassica plants. The research programme has involved collaborations with valued colleagues at the University of Warwick, particularly Dr Guy Barker, Dr Carol Jenner and Dr Jay Moore, and colleagues in Canada, China, Taiwan, Japan, Holland and Spain, culminating with BBSRC-funded, Warwick PhD student Charlotte Nellist completing the final piece of the jigsaw.
"The nature and mechanism of the resistance suggests that unlike many forms of plant resistance to disease, this particular resistance has the potential to be durable."
Reference: Multiple copies of eukaryotic translation initiation factors in Brassica rapa facilitate redundancy, enabling diversification through variation in splicing and broad-spectrum virus resistance. http://onlinelibrary.wiley.com/doi/10.1111/tpj.12389/abstract
Exploitation Route As explained above, the findings are being taken forward by a commercial seed company who have purchased the rights to our patent and are pursuing it worldwide. They are also introgressing our novel broad-spectrum virus resistance in to commercial plant varieties. It is anticipated new varieties based on our resistance will be released in 2022.
Sectors Agriculture, Food and Drink,Education,Environment

 
Description BBSRC-funded researchers have described a mechanism conferring resistance in brassica plants to Turnip mosaic virus, a discovery which it is hoped will lead to durable resistance being introduced in to food crops. The University of Warwick, Chinese Academy of Agricultural Sciences and Syngenta Seeds team report their finding in The Plant Journal. Turnip mosaic virus (TuMV) can infect all kinds of plants, including oilseed rape, peas, cabbages, broccoli, Brussels sprouts, turnips, radish and cauliflower; it causes significant damage and losses to crops. TuMV is a member of the largest taxonomic group of plant viruses causing major diseases in most crop plants and hence the discovery has tremendous generic relevance. In their paper the researchers have unravelled the mechanism behind a novel broad-spectrum, recessive and potentially durable resistance to the virus and identified the gene involved. The resistance, which arises from a particular form of a gene called eIF4E, has been shown to be effective against different strains of TuMV from across the world. The University of Warwick has patented the generic resistance mechanism; Syngenta Seeds have purchased the generic patent and are currently introducing the resistance gene into commercial varieties of brassicas via a breeding programme. The breeding programme has been speeded up dramatically by the identification of the gene at Warwick, this has allowed Syngenta to use marker-assisted selection for the gene. Pre-commercial field trials are planned for 2016. Lead investigator Dr John Walsh, from the University of Warwick, said: "This is the culmination of careful and detailed research built on in depth knowledge of the virus and its interactions with brassica plants. The research programme has involved collaborations with valued colleagues at the University of Warwick, particularly Dr Guy Barker, Dr Carol Jenner and Jay Moore, and colleagues in Canada, China, Taiwan, Japan, Holland and Spain, culminating with BBSRC-funded, Warwick PhD student Charlotte Nellist completing the final piece of the jigsaw. "The nature and mechanism of the resistance suggests that unlike many forms of plant resistance to disease, this particular resistance has the potential to be durable." Syngenta anticipate release of commercial plant varieties possessing the virus resistance discovered at Warwick by 2022. Reference: Multiple copies of eukaryotic translation initiation factors in Brassica rapa facilitate redundancy, enabling diversification through variation in splicing and broad-spectrum virus resistance. http://onlinelibrary.wiley.com/doi/10.1111/tpj.12389/abstract. Patents have been filed by the University of Warwick: patent WO 2011/161466 A1, https://patentimages.storage.googleapis.com/9a/4a/0d/d605689db7248c/WO2011161466A1.pdf and Syngenta US 2013/0117879 A1, https://patents.google.com/patent/US20130117879/en
First Year Of Impact 2010
Sector Agriculture, Food and Drink,Education,Environment
 
Description I was invited to and participated in the UK-US Plant Health Workshop organised by BBSRC, USDA, UK Science & Innovation Network, Research Councils UK United States and the US National Institute of Food and Agriculture in the British Embassy on 19-21 September, 2016. The workshop produced a white paper 'Foundational and Translational Research Opportunities to Improve Plant Health', Molecular Plant-Microbe Interactions 30 (7).
Geographic Reach North America 
Policy Influence Type Membership of a guideline committee
URL https://apsjournals.apsnet.org/doi/pdf/10.1094/MPMI-01-17-0010-CR
 
Description Invited to and participated in the Industrial Strategy Challenge Fund Workshop - Agricultural Productivity held in Solihull on 15 August, 2017 attended by industry representatives, BBSRC, NERC, academics, levy boards etc.
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description Invited to and reviewed the Scottish Government's portfolio of strategic research, 2015.
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description BBSRC iCASE studentship
Amount £111,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2015 
End 09/2019
 
Description Warwick Impact Fund
Amount £45,643 (GBP)
Funding ID 15LFHF02 
Organisation University of Warwick 
Sector Academic/University
Country United Kingdom
Start 08/2017 
End 07/2019
 
Title Broad-spectrum resistance 
Description Plant lines with broad-spectrum, potentially durable disease resistance along with within-gene molecular markers. 
Type Of Material Biological samples 
Year Produced 2010 
Provided To Others? Yes  
Impact Syngenta are introgressing the gene conferring the broad-spectrum disease resistance into commercial plant lines, utilising the molecular markers we jointly developed. 
URL http://www.bbc.co.uk/programmes/b00vy38g
 
Description Syngenta CASE studentship 
Organisation Syngenta International AG
Country Switzerland 
Sector Private 
PI Contribution PhD studentship outputs
Collaborator Contribution Plant lines for crossing to and molecular marker services
Impact Identity of gene involved in broad-spectrum disease resistance
Start Year 2009
 
Description Syngenta material purchase 
Organisation Syngenta International AG
Country Switzerland 
Sector Private 
PI Contribution Provided plant germplasm with broad-spectrum disease resistance
Collaborator Contribution A route to exploitation / commercialisation
Impact Reported eslsewhere in Researchfish
Start Year 2009
 
Title Plant eukaryotic translation initiation factor 4E 
Description Novel form of resistance to a plant virus 
IP Reference WO2011161466 
Protection Patent granted
Year Protection Granted 2011
Licensed Yes
Impact Syngenta Seeds are pursuing the patent worldwide.
 
Description CSI dissemination / publicity 
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 Media (as a channel to the public)
Results and Impact Radio 4's Science programme 'Material World' with Quentin Cooper:
http://www.bbc.co.uk/programmes/b00vy38g

An article on our research was published in the Guardian:
http://www.theguardian.com/education/2010/dec/07/christmas-sprouts-black-spots-scientists

An article on our research was published in the Daily Telegraph:
http://www.telegraph.co.uk/topics/christmas/8143302/Brussel-sprout-will-be-resistant-to-black-spot.html

A Warwick iCast:
http://www2.warwick.ac.uk/newsandevents/icast/archive/s2week19/vegvirus/
Year(s) Of Engagement Activity 2008,2010
URL http://www.bbc.co.uk/programmes/b00vy38g
 
Description Challenges for Crop Production & Quality, Annals of Applied Biology Centenary Conference, Rothamsted, Harpenden 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Centenary meeting to celebrate 100 years of the Annals of Applied Biology attended by senior researchers, industry etc. where I was able to highlight outcomes of BBSRC CSI project and BBSRC iCASE studentship
Year(s) Of Engagement Activity 2014
URL http://www.aab.org.uk/images/annals_centenary_pbf.pdf
 
Description Fascination of Plants Day 
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 We had an exhibit at the Fascination of Plants Day on May 18th 2017 at our campus.
Year(s) Of Engagement Activity 2017
URL https://warwick.ac.uk/study/outreach/news/celebrating_fascination_of/
 
Description Innovate UK Industrial Strategy Challenge Fund Workshop - Agricultural Productivity 
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 I participated in Innovate UK's Industrial Strategy Challenge Fund Workshop - Agricultural Productivity at the Ardlen Hotel, Solihul on 15 August, 2017.
Year(s) Of Engagement Activity 2017
 
Description International Advances in Plant Virology conference (London) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A poster presented by PhD student Lawrence Bramham at this international conference focussed on advances in virus research at which I was a member of the organising committee.
Year(s) Of Engagement Activity 2016
URL http://www.aab.org.uk/images/virology_2016_ann_pbf.pdf
 
Description International Advances in Plant Virology conference (London) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A talk by PhD student Tongtong Wang at this international conference focussed on advances in virus research at which I was a member of the organising committee.
Year(s) Of Engagement Activity 2016
URL http://www.aab.org.uk/images/virology_2016_ann_pbf.pdf
 
Description International Advances in Plant Virology conference (London) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A poster presented by Brazilian collaborator Dr Marcelo Eiras at this international conference focussed on advances in virus research at which I was a member of the organising committee.
Year(s) Of Engagement Activity 2016
URL http://www.aab.org.uk/images/virology_2016_ann_pbf.pdf
 
Description Invited presentation at Centro de Biotecnología y Genómica de Plantas (CBGP, UPM-INIA). Campus Montegancedo. Autopista M-40, km 38. Pozuelo de Alarcón. 28223 Madrid. Spain. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Invited presentation at Centro de Biotecnología y Genómica de Plantas (CBGP, UPM-INIA). Campus Montegancedo. Autopista M-40, km 38. Pozuelo de Alarcón. 28223 Madrid. Spain.
Year(s) Of Engagement Activity 2017
URL http://www.cbgp.upm.es/files/seminarios/SEMINARIOS_CBGP_2016_17.pdf
 
Description Invited seminar, University of York 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Invited seminar presentation at Univewrsity of York, 17th April, 2018.
Year(s) Of Engagement Activity 2018
 
Description Keynote conference presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Keynote presentation entitled 'The quest for durable plant diease resistance' at the 10th International Virology Summit, 2-4 July, 2018 in Vienna, Austrai.
Year(s) Of Engagement Activity 2018
URL https://virology.conferenceseries.com/europe/2018/
 
Description Midlands Integrative Biosciences Training Partnership (MIBTP) BBSRC Doctoral Training Partnership Student Symposium Invited Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Midlands Integrative Biosciences Training Partnership (MIBTP) BBSRC Doctoral Training Partnership Student Symposium Invited Presentation
Year(s) Of Engagement Activity 2017
 
Description Public engagement event Gibbet Hill 
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 A display at School of Life Sciences, University of Warwick public engagement event
Year(s) Of Engagement Activity 2017
URL http://www2.warwick.ac.uk/fac/sci/lifesci/outreach/next/
 
Description The Elizabeth Creak Charitable Trust Warwick Food Security Lecture; Keeping Pathogens at Bay 
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 Poster and plant exhibit at The Elizabeth Creak Charitable Trust Warwick Food Security Lecture; Keeping Pathogens at Bay outreach activity.
Year(s) Of Engagement Activity 2017
URL https://warwick.ac.uk/fac/sci/lifesci/outreach/publicscievents/programme_for_event_final.pdf
 
Description UK-US Plant Health Workshop to discuss plant health and develop a white paper 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact the UK-US Plant Health Workshop held in the British Embassy, Washington DC was held to discuss biotic challenges to plant health and develop a white paper for future directions of research.
Year(s) Of Engagement Activity 2016
URL https://apsjournals.apsnet.org/doi/full/10.1094/MPMI-01-17-0010-CR
 
Description UK-US Plant Health Workshop, British Embassy, Washington DC 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact A UK-US workshop to:
- facilitate new collaborations and build on existing links
- increase community knowledge for international research collaborations
- inform future funding priorities
Year(s) Of Engagement Activity 2016
 
Description University visit (Saga University, Japan) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact Visit to Saga University, Japan, 18-24th May, 2019. Lecture to undergraduate and post-graduate students and discussions with postgraduate (MSc and PhD) students.
Year(s) Of Engagement Activity 2019
 
Description Video, open day JW YouTube 
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 A video to highlight the outcomes of the BBSRC funded projects
Year(s) Of Engagement Activity 2014
 
Description Virology conference, Haarlem, The Netherlands 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact An oral presentation by PhD student Tongtong Wang at the international conference focussed on virus disease of legumes and vegetables at which I was the president of the group.
Year(s) Of Engagement Activity 2015
URL http://www.plant-virology.nl/IWGLVV2015/
 
Description Virology conference, Haarlem, The Netherlands 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact An international conference focussed on virus disease of legumes and vegetables at which I was the president of the group.
Year(s) Of Engagement Activity 2015
URL http://www.plant-virology.nl/IWGLVV2015/