Yield losses in agriculture

1
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

2
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

3
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

4
Traditional disease control measures

• Chemicals broad spectrum, but
• Expensive
• Hard to distribute
• Safety concerns
• Evolution of pathogen resistance, sometimes
  quickly

5
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

6
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
2.6
2.7
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
7
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

8
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

9
Two Blades Mission

• To support the development and deployment of
  durable disease resistance in agricultural crops

10
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

11
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

12
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

13
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

14
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

15
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

16
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

17
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

18
Field Test

• VF36

• VF36 Bs2

19
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

20
Plant Strategic Defense Initiative (PSDI)

• Explore the hypothesis that durable non-host
  resistance can be found and/or engineered by
  stacking R genes

21
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?

22
A Pyramid of R genes?
23
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

24
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

25
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

26
PSDI Potential targets

• Wheat stem rust
• strain Ug99

Photo by Cereal Disease Lab, USDA
27
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 NBLRR
  genes from wild wheat relatives, rice, or
  Brachypodium distachyon

28
PSDI Other potential targets

• Asian soybean rust
• (Phakopsora pachirhizi)
• 700MM fungicide replacement value
• endemic throughout southern Asia

http//www.uky.edu/Ag/Agronomy/CropEcoPhys/kumudin
i/projects.htm
29
PSDI Other potential targets
http//www.apsnet.org/education/feature/banana/

• Black sigatoka in banana (Mycosphaerella
  fijiensis)
• gt200MM fungicide replacement value endemic in
  sub-Saharan Africa

30
PSDI Other potential targets

• Xanthomonas bacterial wilt of banana and enset

www.bspp.org.uk/ndr/july2005/2005-29.asp