STAVCON 2003

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FEAST Conference 2006 Research Without
Borders Agricultural BioScience Technology
Developments and Applications in the Post-Genome
EraG Spangenberg
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Bio(techno)logy Some History
1865 Mendel Laws of inheritance from
statistical inference
1944 Avery/MacLeod/McCarty DNA hereditary
material
1953 Watson/Crick DNA double helix
1965 Restriction enzymes DNA scissors
1966 Nirenberg/Khorana/Holley Determine genetic
code
1972 Cohen/Boyer Recombinant DNA, gene transfer
in bacteria
1977 Sanger/Maxam/Gilbert DNA sequencing methods
1982 Insulin produced by transgenic bacteria
1985 Polymerase Chain Reaction (PCR)
1991 First transgenic animal Herman the bull
1994 GM tomato to market
1997 First cloned animal Dolly
2000 Human Genome Project completion announced
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Our Ability to Generate, Use and Transfer
Knowledge...
Johannes Gutenbergc. 1400
Chinese alphabetc. 1500 BC
from 10,000 characters ...
to 26 characters...
Gutenberg Bible
determined the success of our civilizations
...
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to 2 characters.
the dominant civilization and itseconomy
uses ...the Digital Alphabet...
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and the Genetic Alphabet!
with 4 characters.
Guanine
Cytosine
Thimidine
Adenine
The Genome Era - enabled through the Omics
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The Genome Era
Human 2001
Rat 2003
Rice 2002
Mouse 2002
Arabidopsis 2000
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...Genome Sequences Complete or Available
Soon...
Currently 235 eukaryotic genome sequencing
projects complete or in progress (draft assembly
stage)
36 plant species
91 animal species
human Caenorhabditis Drosophila mouse
Arabidopsis thaliana rice
Brassica lucerne corn wheat tomato potato grape po
pulus
honey bee rabbit cow dog cat chimpanzee chick
en tammar wallaby
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Genome Sequence and Variation in Bovine Breeds

• 3,651 Mb genome size
• 1.4 million sequences
• 2.4 billion bases
• 2 million SNPs - 7 breeds

• Dramatically changes research approaches in
  livestock genetics and improvement

• Genome sequences of strains and individual
  organisms

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The Omics Revolution...
The Industrial Scale Discovery of Genes and Their
Functions ...
towards Understanding ...
RNAi
...Large Scale Biology.
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Discovery-Driven...
Genome (DNA level) - Genomics
Transcriptome (mRNA level) - Transcriptomics
Proteome (protein level) - Proteomics
Metabolome (metabolite level) - Metabolomics
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Technology-Intensive...
High-Throughput DNA Sequencing
Biorobotics
...from few genes per year to thousands per day!
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Arrays for SNP Detection and Genotyping
High-Throughput SNP Detection (Sequenom)
One wafer holds 60,000,000 DNA probes
(Perlegen) Can measure 2 million SNPs across the
genome.
Scanning of
200,000 individuals per hour
384 reactions per hour
500 individuals per reaction
throughput enabling to genotype 12 million
samples in 1 week!
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TranscriptomeAnalysis Using Microarrays ...
...Knowledge-Intensive!
...from 1 gene to 30,000 genes studied in
parallel.
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Dissecting Transcriptomes...
Experimental Conditions
Experimental Conditions

• Differential gene expression
• Roots and shoots
• Seedling development
• Expression patterns (seed vs shoot) mapped
  to metabolic processes

Gene Clusters

• Increased levels in seed

• Increased levels in shoot

Roots
Shoots
Roots
Shoots

• 15K unigene array
• Template gene aquaporin

• 78 genes with equivalent expression profile

• Robust measurements of biological parameters

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Bioinformatics for Analysis from Nucleotide to
Phenotype

• Integration of physical and functional annotation
• Co-location of QTLs and functionally associated
  genetic loci
• Integration from genome through transcriptome to
  phenome
• Improved selection for candidate genes

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Biology Becomes an Information Science ...
Huge Distributed Datasets ...
Large Interaction Network
Highly interconnected - giant component
Website-based 5-6 clicks away!
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The Virtual Plant
Arabidopsis 2010 Program
Whole-system approach to the study of plant form
and function

• Understanding the function of all genes of a
  reference species within their cellular,
  organismal and evolutionary context

• Understanding of every molecular interaction in
  every cell throughout a plant lifecycle

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From Large Scale Biology to Systems Biology
Molecule-based cell and organism simulations
Molecular machine simulation
Community metabolic regulatory, signaling
simulations
Current Capability
Cell, pathway and network simulation
Genome-scale protein threading
Comparative genomics
Biological Complexity
Path from basic genome data to a more detailed
understanding of complex molecular and cellular
systems - well beyond model organisms
Need for new computational analysis, modelling
and simulation capabilities
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Simulations of Biological Systems from
large-scale biology to systems biology

• Technology- knowledge-intensive

• Computation-demanding

• We can predict unanticipated influences from
  advances in and applications of high-tech

• We can predict surprising breakthroughs in
  bio(techno)logy will occur

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improving the food we eat.
Will This Impact on Our Lives?
improving the competitiveness of our
agricultural production systems.
improving the environment we share.
meeting the challenges of feeding the world.
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Feeding the World

• Current level of food production is 5 billion
  tons per year

• Human population doubled since 1960 to 6 billion

• World population predicted to increase to 8
  billion by 2030 and to 9 billion by 2050

• In next 2 generations the world will consume
  twice as much food as consumed in the entire
  history of humankind

• Multiple new technologies of food production
  created and adopted to keep up with population
  growth

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Livestock Revolution

• Global population to increase to 7.5 billion by
  2020

• Massive global increase in demand for food of
  animal origin fueled by

• Population growth

• Urbanization

• Income growth in developing countries

• By 2020 global population projected to
  consume 120 million tons of meat and 220
  million tons of milk above current consumption.

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Food Security and the Environment
By 2030 world population will reach 8 billion

• Need for increased crop production

• 12 increase of arable land required

• Deforestation

• Water access, use quality

• Salinity

• Need for reduction in greenhouse gas emissions

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Water - A Limited Resource
km3 pa
Irrigation of arable land
4000
Reservoir losses
Municipal
3000
Industry
2000
Asia 42
1000
Agriculture
Near East and North Africa 31
Latin America and the Caribbean 14
0
Sub-Saharan Africa 4
1940
1900
2000
1960
1980
1920
Worldwide, 70 of all water is used for
agriculture
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Drought Tolerant Wheat

• Transgenic (GM) wheats

• Synthetic wheats

• Estimated additional 292 million tons of cereals
  will be used annually as feed by 2020.

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Malnutrition - Health

• One in five people in the developing world is
  chronically undernourished

• 55 of the 12 million child deaths every year
  relate to malnutrition

• More than 2000 million people worldwide suffer
  from micronutrient deficiencies

• Anaemia 2000 million

• Iodine deficiency 740 million

• Vitamin A deficiency 228 million children

• Obesity and chronic diseases number of
  overweight people rivals number of underweight
  people

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Global Status of GM Crops (2005)
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Global Impact of GM Crops (2005)

• 2005 was tenth planting season of GM crops

• Cumulative US27 billion net economic
• benefits at the farm level

• Reduced pesticide spraying by 172 million kg

• 14 reduced environmental footprint associated
• with pesticide use

Golden Rice
Golden Rice

• Significant reduction of greenhouse gas emission
  
• (equivalent to removal of 5 million cars)

• And more to come..

Drought Tolerant Wheat
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Genomics has Created a New Paradigm

• Past

• Specific Genes

• Phenotype

• Present

• All Genes

• New Phenotypes

Gene discovery will not be rate limiting
(translational genomics genomics in
post-genomics era)
Scientific understanding of plants and animals
will thrive over the next 20 years
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Genomic Discoveries into Genetic Solutions

• Unknown Gene ? Known Function
• Known Function ? Useful Technology
• Useful Technology ? Valuable Products for
  Markets

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Omics Technologies in Molecular Breeding
Predictive
Broader view of agbio sciences as agricultural
systems biology will emerge
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Smart Breeding Will Create New Value in
Agriculture and Livestock Production
Genomics
Enhanced products Novel traits Integrated
production solutions
Bioinformatics
Health nutrition benefits Food processing
economics Consumer appeal Agronomic benefits
Functional Metabolomics
Molecular Breeding
Functional Genomics
Public good breeding Delivery of societal
benefits.
Understanding Engaging the Value Chain
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• Improved human health

• Pest disease resistance

• Enhanced animal
• health welfare

• Better quality crops

• Healthy oils
• starches

• Biosecurity
• bio-industry applications

• Enhanced yields

• Abiotic stress tolerance

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dias

• Improved environmental health

Public will have to weigh up the negative
perception of GM foods against the risks for the
planet of not producing them
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Understanding Genetic Influences on Biological
Systems Useful genetic modifications for plants
and animals

• better quality crops pastures

• pest disease resistance

• reduced reliance on agrochemicals

• abiotic stress tolerance

• novel bio-industry uses

? Crops caring for the environment
? Food for health - personalised nutrition
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Biosphere Genomics
Sequencing the Environment
Oceans River systems Gut and rumen Soils Air Plan
ts Animals
Rio Tinto and Iron Mountain microbial community
metabolism
Ocean (Bermuda) 1.2 million new genes 700
light-driven proton pumps
boiling thermal acquifers
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Biosphere GenomicsDesigning Crops for Abiotic
Stress Tolerances
Antarctic Hair-GrassDeschampsia antarctica
One of only two antarctic vascular plants

• Freezing tolerance

• Desiccation tolerance

Up to 15 of agricultural production is lost to
frost each year.
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Biosphere GenomicsOptimising Bioenergy
Production from Biomass
Improved Ethanol Producing Organisms

• Improved Feedstocks
• Increase agricultural yield
• Increase enzymatic susceptibility

• more efficient conversion
• higher ethanol tolerance

• Saccharomyces cerevisiae
• Zymomonas mobilis
• Thermoanaerobacter ethanolicus
• Pichia stipitis

• Cellulosic Materials
• Cereal Stover
• Poplar
• Switchgrass

Saccharification
Sugars
Fermentation
Improved Breakdown of Biomass

• Termite hindgut microbiota
• Wood digesting fungi
• Nasutitermes corniger
• Saccharophagus degradans
• Acidothermus cellulolyticus

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Synthetic Biology

• Molecular evolution by DNA shuffling

Evolving 100-10,000fold in enzyme activities
Mimic chemical pathways for the development of
plant-derived drugs
Use molecular machineries in microorganisms to
efficiently capture energy stored in
lignocellulosic biomass

• Understand and design biological systems and
  their components

Engineering microorganisms to remediate
environmental contaminants

• Advance foundational understanding and
  technologies to build biological components and
  assemble them into integrated systems

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Summary

• Biology becomes an information science
• simulations of biological systems from large
  scale biology to systems biology
• Understanding genetic influences on biological
  systems
• useful genetic modifications in plants and
  animals
• A revolution in the utility of biological
  systems
• biological diversity enables a revolution in
  protein/organism design and application
• Participation requires new levels of
  collaboration, connectivity, resource
  coordination and excellence