CS2 Technologies to control plant parasitic nematodes
Submitting InstitutionUniversity of Leeds
Unit of AssessmentBiological Sciences
Summary Impact TypeTechnological
Research Subject Area(s)
Biological Sciences: Genetics, Plant Biology
Agricultural and Veterinary Sciences: Crop and Pasture Production
Summary of the impact
Plant resistance provides sustainable control of the $125bn annual world
crop losses to nematodes to replace environmentally hazardous pesticides.
Urwin and Atkinson have developed three biosafe resistance
technologies that 1) suppress feeding success, 2) reduce root invasion and
3) suppress nematode development by RNA interference. We have developed GM
agriculture with leading industry (Sinochem, Monsanto) and in emerging
economies through free access to technology, capacity building
initiatives, review of collaborative R&D plans (India) and regulatory
approval of field trials (Uganda). The work has also influenced
policy-makers in the UK and in Switzerland, leading to new security
measures for GM field trials in these countries..
Plant parasitic nematodes cause global crop yield losses of $125bn
annually (1). Nematicides can cause harm to humans in their
production and use but it is their severe environmental harm that is
leading to their withdrawal globally, often leaving farmers without
adequate nematode control. The partnership of Urwin (molecular
lead) and Atkinson (biological lead) and co-workers have developed
three technologies for nematode control from discovery to field evaluation
in a continuous on-going collaboration that dates from before 1993. This
case study is underpinned by over 50 awards to them with a value in excess
Cysteine proteinases are important digestive enzymes for nematodes but
not humans that are inhibited by cystatins. Plant cystatins are widely
consumed in foods (e.g. maize and rice) and are neither human allergens
nor toxins. Transgenic expression of a protein engineered cystatin
provides nematode resistance (2,3) with efficacy against all
damaging nematodes tested in a wide range of crop plants.
The technology has been proven in five UK field trials with potato plants
(4). The work at Leeds is internationally distinctive by providing
the only published reports of GM field trials for nematode resistance. It
can take 15 years between proof of concept and commercialisation of new GM
technologies. We have had funding in that phase of the work by companies
including Limagrain, Ingleheim Boehringer, Zeneca, Syngenta, Harris Moran
Del Monte, Dole and Maui Pine. The cystatin-based technology is currently
being commercialised for cotton by China Seeds (Sinochem). Our field
trials also established that potato plants expressing Technology 1 do not
harm non-target, insect aerial feeders, their natural parasitoid enemies
or the soil microbial communities (5).
This invention is based on novel synthetic peptides and a novel uptake
pathway we showed along certain nematode chemoreceptive neurons. Peptide
uptake leads to the targeted nematodes being unable to sense the proximity
of roots but it is not lethal to them and hence harmless to nematodes in
the soil community that do not attack roots. Transgenic expression of the
peptide protects potato (6) and banana plants from nematode
invasion and its associated root damage. Faunal analysis using a
bar-coding approach establishes no harm to the non-target nematode soil
We have characterised and utilised promoters that restrict expression of
these defences to where in roots nematodes invade or feed. This limits the
presence of the novel protein or peptide in the crop, ensuring absence of
the expressed GM trait in the yield and adds a large margin of safety to
the inherent biosafety of our proteins and peptides. We have also shown
any likely levels of protein or peptide ingestion is not harmful to
Atkinson and Urwin were the first to show that RNA
interference is an effective gene silencing approach for plant parasitic
nematodes (1). We have demonstrated that transgenic expression of
double-stranded RNA in the host plant interferes with expression of
targeted nematode genes so disrupting nematode development. The benefit is
a nematode resistant GM crop control without any novel protein production.
Lead academics: Professor P Urwin (Professor of
Nematology, co-PI, 1993-present); Professor H Atkinson (Professor of
Nematology, co-PI, 1972-present)
Academic collaborators: (all University of Leeds) Prof B.H.
Davies (1996-present); Prof P.M. Gilmartin (1991-2007); Prof J.P Knox
(1991-present); Prof M.J McPherson (1982-present); Prof P. Meyer
(1995-present); Dr S. Kepinski (2006-present).
Postdoctoral Researchers at Leeds: Catherine Lilley
(01/2004 — current); Laura Jones (07/2009 — current); Sarah Cowgill
(01/1996 — 06/2000): Mirela Coke (08/2010 — current); Kate Warner (08/2009
— current); Hugh Roderick (06/2008 — current); Anil Neelam
(07/1999-11/2000); Manjula Bakhetia (08/2003 — 08/2009); Jayne Green
(07/1999 — 01/2009); Elena Zubko (10/1997-09/2000).
References to the research
1. Urwin PE, Lilley CJ, and Atkinson, HJ. (2002) Ingestion of
double-stranded RNA by preparasitic juvenile cyst nematodes leads to RNA
interference. Molecular Plant-Microbe Interactions 15:747-752
DOI: 10.1094/MPMI.2002.15.8.747 [Scopus citations (30/08/2013): 147]
2. Urwin, PE, Atkinson, HJ, Waller, DA, and McPherson, MJ. (1995)
Engineered Oryzacystatin-I Expressed in Transgenic Hairy Roots Confers
Resistance to Globodera pallida. Plant Journal 8:121-131.
DOI: 10.1046/j.1365-313X.1995.08010121.x [Scopus citations
3. Urwin PE, Lilley CJ, McPherson MJ, and Atkinson HJ. (1997) Resistance
to both cyst and root-knot nematodes conferred by transgenic Arabidopsis
expressing a modified plant cystatin. Plant Journal 12:455-461.
DOI: 10.1046/j.1365-313X.1997.12020455.x [Scopus citations
4. Urwin PE, Green J, and Atkinson HJ. (2003) Expression of a plant
cystatin confers partial resistance to Globodera, full resistance
is achieved by pyramiding a cystatin with natural resistance. Molecular
Breeding 12:263-269. DOI: 10.1023/A:1026352620308 [Scopus
citations (30/08/2013): 31]
5. Celis C, Scurrah M, Cowgill SE, Chumbiauca S, Franco J, Main G,
Keizenbrink DT, Green J. and Atkinson HJ. (2004) Environmental biosafety
and transgenic potato in a centre of this crop's diversity. Nature
432:222-225. DOI: 10.1038/nature03048 [Scopus citations
6. Green J, Wang D, Lilley CJ, Urwin PE, and Atkinson, HJ. (2012)
Transgenic potatoes for Potato Cyst Nematode control can replace pesticide
use without impact on soil quality. Public Library of Science ONE
7:e30973. DOI: 10.1371/journal.pone.0030973 [Total article views
= 3,357 (21/10/2013); Scopus citations (30/08/2013): 3]
Selected grants awarded: Genome sequence for the potato
cyst nematode Globdera pallida, BBSRC reference BB/F000642/1,
01/03/2008-31/08/2012, £425k, PI Urwin; Nematode resistant plantain for
Africa subsistence growers, BBSRC reference BB/F004001/1,
18/06/2008-17/06/2011, £523k, PI Atkinson; Functional characterisation of
novel pathogenicity genes of the parasitic nematode Globdera pallida,
BBSRC reference BB/H000801/1, 01/07/2010-30/06/2013, £343k, PI Urwin;
Development of improved East African Highland Banana, US Agency for
International Development, 01/10/2006-31/05/2015, £288k, PI Atkinson.
Details of the impact
Strategy for delivering impact.
Urwin, Atkinson & colleagues recognised that their research impacted
on many of the critical issues of food security (maximise production,
minimise environmental impact, address public concerns). Their patenting
and licensing strategy allowed new product development in collaboration
with multinational agricultural companies and simultaneous independent
collaboration with authorities in developing economies to establish home
grown expertise and capability in GM crops. They also engaged with
policy-makers and the public to inform and influence the debate concerning
GM safety and use as a solution in food security.
Interactions with Industry:
i) They have been underpinned by patents granted to the University
(>12 granted patents, e.g. publication numbers: PL362116; HK1032073;
AU6063999; CZ20002005; US2001016954; GR3026133; US2003221209; US5863775;
US5824876; EP1231274; AU691020; US5589622).
ii) Opportunities are international given UK agriculture produces only 1%
of the world crop harvest. The largest seed company in China (China seeds,
Sinochem) is funding us (2012-2015, value £500k) to develop nematode
resistant cotton [A] (Technology 1) as one of the first
technologies in their newly formed plant biotechnology unit. Monsanto
bought a licence to key USA crops, under a patent filed by the University
of Leeds (Technology 3) and has made several payments totalling £44,000 to
the University since 2008 [A]. Technology 1 is being put into
crops to confer nematode resistance for pineapple, coffee and flowers in
USA (Hawaii Agriculture Research Center, (HARC), Beltsville Agricultural
Research Center) and aubergine and rice in India (Indian Agricultural
Research Institute, (IARI)) [B].
Influencing Government policy:
i) Our recommendation to have protected national field-trial sites
(Atkinson & Urwin 2008, Nature 453, 979) has led to the Swiss
government establishing such a scheme [C]. We were invited to meet
the Minister for the Environment (August, 2008) who subsequently publicly
supported our research. The Secretary of State for Environment, Food &
Rural Affairs cited our work in the House of Commons as an exemplar of
research to address the critical questions concerning GM food (namely,
"what is the impact on biodiversity?") [C].
ii) Atkinson gave evidence to the UK Parliamentary and Scientific
Committee in 2010 concerning the potential of GM crops to enhance global
food security, drawing on Urwin/Atkinson research on GM strategies to
combat potato cyst nematode (references 1-6) [D]. He also
contributed to, and reviewed, a government publication on GM crops [E].
i) The expertise has been applied internationally. Atkinson co-chaired
(December 2011) an evaluation of the 3rd phase of the
Indo-Swiss Collaboration in Biotechnology (2007-2012, expenditure £6.9m,
circa 25 project partners) at the request of the Department of
Biotechnology, The Ministry of Science and Technology, India [F].
The detailed recommendations shaped the 4th phase (2013-) of
this international collaboration.
ii) Drawing on knowledge gained from consents granted by DEFRA to Urwin
and Atkinson for their UK field trials (e.g. 09/R31/01, 07/R31/01;
references 5 and 6), Atkinson was also a major contributor to the
successful submission by The National Agricultural Research Organisation
of Uganda to that country's National Biosafety Committee for the first
field trials of GM bananas and plantains for nematode control [G].
The trials were subsequently planted in 2012.
iii) Strategic work is currently centred on cotton for deployment in
China [A] and, in collaboration with other institutes, plantain
and cooking bananas in Uganda (Technologies 1 and 2, National Agricultural
Research Labs, Uganda) and Kenya (International Institute of Tropical
Agriculture). Researchers using Technology 1 are developing nematode
resistant pineapple in Hawaii (HARC) [B] and rice and aubergine in
iv) The work on cooking bananas is central to our effort to develop
public goods (Technologies 1-3). This crop suffers estimated losses to
nematodes in Africa of 71 ±16% and is vital food for 100 million, mainly
poor, Africans. The crop's sterility and slow improvement by traditional
cross-pollination techniques underpin its value for GM based improvement.
Transgenic bananas with our nematode resistance are in authorised field
trials in Uganda following planting in 2012. Our expertise (funded by
BBSRC, RCUK, DFID, EU and USAID [H]) has enabled scientists in
Uganda and other developing countries to deliver these benefits. We have
hosted capacity building programmes for >20 scientists from developing
countries funded by DFID, BBSRC (e.g. SARID initiative, BB/F004001/1 and
ISIS1873), The Foreign and Commonwealth Office (470529) and USAID
(APSPII). We donate technology through DFID, USAID, BBSRC and RCUK to
provide public goods for Sub-Saharan Africa and India.
The work has led to numerous radio interviews (e.g. BBC Radio 4 Farming
Today) and television appearances (e.g. BBC's Countryfile,
2009, and the Channel 4 programme What the green movement got wrong,
2010). Our work has been widely reported in newspapers, (e.g. a major
article in the Sunday Times Magazine [I] and The Financial Times [I])
and included in an exhibition at the Science Museum in London.
Sources to corroborate the impact
[A] Contract between Sinochem and University of Leeds, detailing
the work to be carried out to develop nematode resistant cotton, and grant
information indicating funding of £500,000 (copies available on
request). Licence payments from Monsanto of £44,000 in REF period (copy
of contract and invoices available on request).
[B] Genetic transformation of crop and flower species using
Technologies 1-3: Wang, M.L. et al. (2009) Production of transgenic
pineapple (Ananas cosmos) plants via adventitious bud
regeneration. In vitro cellular and developmental biology — plant
45(2):112-121 DOI: 10.1007/s11627-009-9208-8; Cabos, R.Y. et
al. (2007) Plant proteinase inhibitors as a natural and introduced
defense mechanism for root-knot nematodes in Coffea arabica. Journal
of Nematology 39(1):100 ISSN: 0022-300X; Fitch, M.M.M. et
al. (2011) Improved transformation of Anthurium. HortScience
46(3):358-364 ISSN: 0018-5345.
[C] Romeis, J. et al. (2013) Plant biotechnology: Research
behind fences.Trends in Biotechnology. 31(4):222-224 DOI:
10.1016/j.tibtech.2013.01.020. Hansard 6th Nov 2008: Column
347: T8  and reply from The Secretary of State for Environment,
Food and Rural Affairs (copy available on request).
[D] Meeting took place 15 December 2009 at Portcullis House,
London. Published as Atkinson H.J. (2010) Come back GM — All is forgiven.
Science in Parliament 67, 27-28 (copy available on
[E] Houses of Parliament : Parliamentary Office of Science and
Technology PostNote #412 GM in Agricultural Development June 2012; http://www.parliament.uk/briefing-papers/POST-PN-412.pdf
Also: email trail evidencing Atkinson's involvement as reviewer of POST
note (copy available on request).
[F] Reference to ISCB evaluation report in IAUA News (Quarterly
Newsletter of Indian Agricultural Universities Association 2011, Volume 11
number 4, (see entry on Indo-Swiss collaboration in biotechnology under
Assam Agricultural University, Jorhat). http://www.iauaindia.org/news_universities_oct_dec11.html
[G] African Agriculture blog.com (2012) Uganda: trials of
nematode-resistant GM banana to begin in 2012 http://www.africanagricultureblog.com/2012/03/uganda-trials-of-nematode-resistant-gm.html
(March 19, 2012).
[H] Agricultural Biotechnology Support Project II, East African
Highland (EAH) banana resistant to black Sigatoka and nematodes (http://www.absp2.cornell.edu/projects/intersect.cfm?productid=23&countryid=8).
[I] Published on 27th June 2010. Why genetically
modified crops are good for us. Sunday Times Magazine, p48-54 (copy
available on request); Published 4th February
2012. Bananas become ripe GM target, Financial Times Magazine http://www.ft.com/cms/s/2/5fa2963e-4c86-11e1-b1b5-00144feabdc0.html#axzz2YSRe1pKk