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Yield losses in agriculture. Abiotic stresses - drought, wind, frost, flood Pests - insects, nematodes, etc Weeds - compete with crop Disease - fungi, bacteria, oomycetes, viruses, post-harvest losses. Disease Control Market. Large Current global fungicide sales = $7billion
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Yield losses in agriculture • Abiotic stresses - drought, wind, frost, flood • Pests - insects, nematodes, etc • Weeds - compete with crop • Disease - fungi, bacteria, oomycetes, viruses, post-harvest losses
Disease Control Market • Large • Current global fungicide sales = $7billion • Disease resistance traits present or sought in all crops • Growing • Asian soybean rust • Increased consumption of fruits and vegetables in developing world • Unsolved problems • Bacterial diseases • Soilborne diseases
Crop Disease • Disease problems are increased with high intensity agricultural practices • Monocultures provide “buffet” for successful pathogen • Narrow genetics base • Pressure on evolutionary arms race • Tremendous specificity in plant-pathogen interaction
Traditional disease control measures • Chemicals: broad spectrum, but • Expensive • Hard to distribute • Safety concerns • Evolution of pathogen resistance, sometimes quickly
Traditional disease control measures • Genetics: narrow spectrum • Limited number of genes in intercrossing species • Desirable traits often linked to bad traits, making breeding difficult and slow • Evolution of pathogen resistance, sometimes quickly
Value shift from chemical to seed & trait US Agricultural Industry Revenue 2003 $8.4 Billion 2008 E $9.1 Billion 1996 $7.6 Billion $0.1 $1.3 $2.7 $2.6 $3.6 $4.5 $3.0 $3.5 $3.8 Biotech Traits Germplasm Crop Chemicals Sources: 1996-2003 Doane Agrotek and Seed Studies; Monsanto estimates
Difficulties with genetic approaches to disease problems • No single “killer app” like Bt toxin or glyphosate to control diseases • Disease control market is widely spread across many small crops • Regulatory costs considered too high to support development in nearly all non-hybrid or “minor” crops
Industry Consequences • Primarily academic institutions pursuing disease resistance • Significant value only given after proof-of-concept in the crop • Dramatic downturn in early stage venture investing 2001 – present • Despite major advances in the lab: • No real innovation in crop disease resistance
Two Blades Mission To support the development and deployment of durable disease resistance in agricultural crops
How we work: • Control key intellectual property • Out-license to seed companies in developed countries for profit • Give free access to IP rights and products to Least Developed Countries • Use profits to fund additional research programs
Two Blades Foundation • Incorporated 20 April, 2004 • Conferred 501(c)3 tax exempt status in December, 2004 • Personnel: • Roger Freedman - Chairman, CEO • Eric Ward - President • Diana Horvath - COO • Michael Pauly - Technical Development
Two Blades Foundation • Scientific Advisory Board • Prof. Jeff Dangl, Univ. North Carolina • Prof. Jeff Ellis, CSIRO • Prof. Paul Schulze-Lefert, Max-Planck, Köln • Prof. Brian Staskawicz, UC Berkeley
Two Blades Activities • Identify areas where novel technology developments may support significant unmet agricultural needs • Drive technology development through grants to investigators and use of contract research organizations • Provide overall project management support
Two Blades Activities • Develop and manage IP portfolios by in-licensing and new filings • Initiate commercial programs for crop improvement • Partner with seed companies for commercial deployment
Bacterial Spot Disease • Most serious disease problem in fresh market tomato industry in the Southeastern USA • unsatisfactory chemical control • losses on the order of 20-30% • Disease has persisted as number 1 problem for 30 years • Significant disease problem in peppers, a closely related plant effectors enhance bacterial growth
BS2 Resistance gene • Bs2-based resistance had strong likelihood of being transferable to tomato • Closely related Solanaceous plants • Bs2-based resistance recognizes a bacterial effector that is important for pathogen virulence • Bacterial fitness decreased in the absence of effector
Pepper Tomato Bs2 (+) Bs2 (-) Bs2 (+) Bs2 (-) • Confers resistance to the bacterial spot pathogen, Xanthomonas campestris pv vesicatoria in pepper • Also confers resistance when transferred into tomato
Field Test • VF36 • VF36 Bs2
Bs2 Commercial Strategy • Avoid use of genetic elements except from tomato and pepper for: • Minimum regulatory concerns • Greatest public acceptance • Make prototype in attractive agricultural variety to be near market- ready for: • Greatest control over responsible deployment • Fastest uptake by seed companies
Plant Strategic Defense Initiative (PSDI) • Explore the hypothesis that durable “non-host” resistance can be found and/or engineered by stacking R genes
PSDI premise • Plant resistance (R) genes recognize components of pathogens (effectors), and trigger hypersensitive reaction (HR) • Pathogens are typically restricted to certain host species • Within a species, differences in resistance are attributable to specific R gene/effector interactions • Do non-host species simply have many R genes that recognize pathogen effectors?
A genomic approach • New approach is driven by: • availability of whole genome sequences • dramatic decrease in sequencing cost • ability to mobilize individual effectors • Identify all candidate effectors from a pathogen • Test in high-throughput fashion against all R genes from a crop
Potential hurdles • R gene has to work across species • Model system may have to be developed (e.g. for banana) • Identifying all effectors from some pathogens will be difficult But: • If validated, approach will be applicable to any crop/pathogen system
PSDI target selection • Technical feasibility • Potential impact on food security in developing countries • Potential market in developed countries ($$ for more research) • Try to maximize overlap
PSDI: Potential targets • Wheat stem rust strain Ug99 Photo by Cereal Disease Lab, USDA
Wheat Stem Rust Ug99 • Already pandemic in E. Africa; present in Iran; headed for Pakistan and India • Understand effector complement of Puccinia graminis • Seek non-host resistance by transfer of NB:LRR genes from wild wheat relatives, rice, or Brachypodium distachyon
PSDI: Other potential targets Asian soybean rust (Phakopsora pachirhizi) • ~$700MM fungicide replacement value • endemic throughout southern Asia http://www.uky.edu/Ag/Agronomy/CropEcoPhys/kumudini/projects.htm
PSDI: Other potential targets • Black sigatoka in banana (Mycosphaerella fijiensis) • >$200MM fungicide replacement value; endemic in sub-Saharan Africa http://www.apsnet.org/education/feature/banana/
PSDI: Other potential targets Xanthomonas bacterial wilt of banana and enset www.bspp.org.uk/ndr/july2005/2005-29.asp