PUTTING A GREEN THUMB ON THE GENOMICS HAND Canadian Research Efforts in Environmental Genomics Prese

1
PUTTING A GREEN THUMB ON THE GENOMICS HAND
Canadian Research Efforts in Environmental
Genomics Presented to

• eGenomics Genomes and the Environment
• NIEeS Workshop
• Cambridge University
• September 5-6 / 2005.

2
Purpose of Presentation

• Introduce importance of environmental genomics to
  Canada
• Outline how Canadian federal government and
  selected universities are organizing themselves
  in support of environmental genomics research
  and development
• Identify some research elements of the current
  opportunity / challenge agenda for selected
  environmental genomics research activities
• Introduce evolving North American / International
  efforts at environmental genomics research
  capacity building
• Set the stage for discussion with you on how we
  can collaborate more fulsomely on complementary
  future environmental genomics research initiatives

3
What is Environmental Genomics?

• Environmental Genomics (EG)bridges the gap
  between genetics, physiology, and ecology
• It involves utilization of a broad range of
  modern molecular techniques such as gene arrays
  and single nucleotide polymorphism (SNP) screens
  to monitor variation in gene structure and
  expression
• EG can pinpoint potentially novel interactions
  between environmental stressors and expression of
  specific human, animal and plant genes

4
What is Environmental Genomics?

• Applies knowledge gained on gene identification,
  structure and expression to environmental
  protection management
• Can rapidly identify species in complex
  environments
• Can indicate how environmental stressors affect
  gene expression in humans, animals plants
• Can demonstrate deleterious effects at molecular
  level before organism-level effects are shown

5
Importance of Environmental Genomics (I)

• Genomics builds upon and enhances traditional
  approaches to environmental toxicology
  determination
• Genomics provides an understanding of organisms
  and biological systems that is a prerequisite for
  understanding environmental change
• A key objective for environmental science is
  improved understanding, identification, and
  prevention of environmental problems
• The behaviour and response of an organism /
  groups of organisms to environmental stressors is
  ultimately controlled by genes and the products
  they encode

6
Importance of Environmental Genomics (II)

• Genomics can provide the next generation tools to
  help protect and manage the environment
• Environmental remediation restoration (e.g.
  plants that can clean up contaminated sites)
• Pollution abatement, prevention detection (e.g.
  identification of soil / water pathogens,
  toxicants)
• Wildlife management conservation biology
  techniques (e.g. genetic barcoding for species
  identification)
• High throughput analysis and identification of
  soil / freshwater / marine microbial community

7
Importance of Environmental Genomics (III)

• Genomics could be critical to examining
  biotechnologys potential impacts on the
  environment, such as
• Unintended properties of genetically modified
  organisms (toxicity, allergenicity)
• Emergence of invasive species
• Displacement of native species
• Spread of new pest species
• Gene transfer occurrence and mechanisms from
  genetically modified organisms to other organisms

8
Why Environmental Genomics and Why Now?

• In the environment, virtually all
  microorganisms exist in complex communities whose
  function as a whole is far greater than the sum
  of what their individual members can achieve..
  Understanding these interactions the ways in
  which microorganisms work together to achieve
  complex tasks will provide insights that can be
  used to address global challenges of energy
  production, improved human and animal nutrition,
  understanding infectious disease mechanisms, and
  furthering environmental remediation and
  restoration
• Source Jay Short President and CEO Diversa
  2004

9
Why Environmental Genomics and Why Now?

• The growth and survival of microorganisms
  drives biogeochemical cycling of elements,
  detoxifies many organic compounds, sequesters
  many inorganic compounds, produces a wide range
  of valuable and renewable industrial compounds,
  makes essential nutrients present in the biomass
  of one generation available to the next
  generation, and maintains the conditions critical
  to all life on earth
• Source ASM 2003

10
CANADIAN FEDERAL GOVERNMENT GENOMICS PLATFORM A
TALE OF TWO CITIES

• Extramural Funding - Genome Canada
• Funding (2002-2005) - 375M (2005-2007) -
  165M
• Obligation Build national technical capacity
  in industry and
• university
  (health, GE3LS agriculture, forestry,
• environment)
• Delivery Five regional nodes supporting
  university /
• industry collaboration
• Intramural Funding (HC, NRC, AAFC, DFO, NRCan,
  EC)
• Funding (1999-2005) (2005-2007) - 20 M/yr (1 M
  to Environment
• Canada)
• Obligation To establish initial genomics R D
  capabilities
• EC Delivery Mechanism Several EC Regional Nodes
  Under Strategic Technology
  Applications of Genomics in the
  Environment Program (STAGE)

11
Environment Canadas Genomics Program Research
Focus

• Identification
• Risk Identification
• The National Water Research Institute (NWRI) is
  developing and applying methods that will use DNA
  microarrays to answer questions about the effects
  of environmental contaminants on the biodiversity
  and function of microbial communities.
• Risk Assessment / Management
• Test Method Development
• The Environmental Technology Centre (ETC) is
  developing standardizing genomic-based
  procedures to ensure more accurate data for
  submission under the New Substances Notifications
  Regulations.
• Environmental Monitoring
• The Pacific Environmental Science Centre (PESC)
  National Wildlife Research Centre (NWRC) are
  using toxicogenomic techniques to link observed
  effects of toxics to specific environmental
  exposures providing improved early warning
  signals to industry regulators.
• Conservation Biology and Wildlife Management
• The Canadian Wildlife Service (CWS) is developing
  and applying genetic markers towards the
  resolution of conservation issues.
• Improved Enforcement Compliance
• The PESC has completed a Pulp and Paper study
  that positively identifies mill effluents that
  are causing endocrine disruptor effects to fish.

12
Toxicogenomic Applications

• Environment Canada BC Labs have created internal
  capacity for all phases of genomic testing, with
  the exception of gene array spotting.
• Focus to use EC existing aquatic toxicological
  methods as platform (Rainbow trout test fry and
  early stage test, new amphibian methods in works)
• Application to chronic endpoint traditional
  methods not sensitive enough to detect molecular
  level toxicity. Good predicator to real world
  effects

13
Development of Microarrays

• Functional/Metabolic
• Targeting catabolic, biogeochemical cycling,
  metal resistance
• Pollutant transformation processes
• Ecosystem health
• Taxonomic
• Targeting 16S rDNA
• Microbial community profiling
• Phylogenetic identification

14
Current Toxicogenomic Projects

• Arrays have been used extensively on testing
  effects of
• Pure chemical testing
• Agricultural runoff
• MWWE
• Pulp Paper effluent, 9 mill survey
• Georgia Basin Action Plan-5 year study EDC
  effects using in-house fish and amphibian gene
  arrays.

15
Wildlife Management Using Genomic Tools

• Focus on the following conservation issues
• How can we delineate discrete population units
  for migratory species?
• What is the effect of selective harvesting of
  males on subsequent population growth?
• What is the conservation significance of
  peripheral populations?

16
Population Genetics for Wildlife Management

• Information obtained from population genetics
• studies can be used to determine
• Population structure and size
• Parentage social structure
• Identification subspecies, sex, individual
  (e.g. forensics)
• Distribution genetic diversity
• Gene flow
• Hybridization
• Population viability
• Evolutionary history
• All information that is important in the design
  of
• effective conservation programs.

17
Toxicogenomics Wildlife Toxicology

• How and why do species differ in sensitivity to
  the effects of environmental contaminants?
• Can we determine which species might be most
  affected by existing new environmental
  contaminants?
• Can we develop better biomarkers?

18
Microbial Test Methods for Assessing
Environmental Fate using Genomic Tools

• Objectives
• To develop in-house expertise and laboratory
  capability for developing genomic-based soil
  testing methods for assessing the potential
  environmental risk of domestic or new microbial
  substances
• To develop standardize genomic-based procedures
  to ensure that notifiers generate more reliable
  accurate data on environmental fate for their
  submissions
• To generate risk assessment data on the 29
  microbial substances listed on the CEPA 1999
  Domestic Substances List (DSL)

19
Barcoding Products and Life
415 1 Billion
1110 100 Billion
20
The Microgenomics Network
21
Identifying Life
22
DNA Barcode
short sequence enabling species discrimination
23
Concordia University / Genome Quebec Enzyme
Systems for Pulp and Paper Industry

• White-rot fungi
• Phanerochaete chrysosporium
• Trametes versicolor
• Lentinula edodes

• Other lignin and pitch degrading fungi
• Gloeophyllum trabeum
• Ophiostoma piliferum
• Corpinus cinereus

• Pollutant degrading fungi
• Aureobasidium pullulans
• Amorphotheca resinae
• Leucosporidium scottii
• Cunninghamella elegans

• Freeze-tolerant fungi
• Chrysosporium pannorum
• Cryptococcus laurentii

• Thermophilic composters
• Thermomyces lanuginosa (600C)
• Chaetomium thermophile (500C)

24
Environment Canada - Genomics Research End Users
Conservation and Protection

• CEPA New Substances Biotechnology
• enumeration, detection, monitoring
• EC Alien / Invasives Initiative
• identification, detection
• Ecosystem Effects of Novel Living Organisms
  (EENLO)
• fate and effects
• CWS Species at Risk and CITES
• Access and Benefit Sharing (ABS)
• Enforcement both ECS and EPS
• NOPP Pollution Detection, Monitoring,
  Surveillance

25
Environmental Genomics and New Stewardship /
Regulatory Challenges

• cohort specific regulations?
• bioavailability vs. total pollutant loading?
• cell lines vs. whole animal testing?
• genetic tests for screening CEPA backlog
• greater specificity for non target organism
  testing?
• fur, feather, feces analysis vs. live capture?
• basis for enforcement efficiency of CITES and SARA

26
Synopsis of Environmental Genomics Research
Experiences 1999-2005

• Potential environmental impacts from applied
  genomics in agroforestry, fisheries, mining, and
  industry
• Low prominence / priority ascribed to
  environmental genomics writ large until recently
• Little recognition outside EC given to
  stewardship issues (regulatory, ethics, IP,
  biodiversity)
• Increasing importance being ascribed to
  environmental genomics smart regulations
• Sub-critical masses of environmental genomics
  capacity across Canada
• Limited current EC capacity in environmental
  genomics against all research areas
• Evidence of tremendous interest for green
  genomics on the horizon and attendant funding
  mechanisms to support basic and applied R D

27
ESTABLISHING FUTURE GENOMICS R D PRIORITIES
ENVIRONMENT CANADA-WORK IN PROGRESS
Whole Range Of Priority Areas We Could Be
Involved In
Potential Future Genomics R D Priorities
Interim Genomics R D Activities

• Identification
• Risk Assessment / Management
• Test method Development
• Environmental Monitoring
• Conservation Biology and Wildlife Management
• Improved Enforcement Compliance

• Contaminated sites remediation / restoration
• Bioprospecting
• Industrial ecology and green chemistry
• Climate change/Bioenergy
• Biobarcoding

28
Pursuit of Future Environment Canada
Environmental Genomics Partnerships

• Organized Canadian Environmental Genomics Network
  Meeting in 1999
• Supported 20 NSERC / CFI Submissions
• Ongoing collaboration and support to several
  provincial government / university genomics labs
• Environment Canada / Genome Canada Environmental
  Genomics workshop 2003
• Canada / US / UK Environmental Genomics Workshop
  Ottawa 2004

29
Proposed Environment Canada Strategy for 2005 ff
Alliance and Convergence

• Continue collaboration with Canadian
  environmental genomics community in calibration
  of long term R D Agenda and federal government
  genomics architecture
• Convene EC intramural STAGE community Nov 05/
  January / 06.
• Enhance EC/ USEPA / USDOE / NIEHS / NERC / NIEeS
  collaboration
• Harvest the results from SETAC, OECD, and NIEeS
  workshops
• Explore establishment of CanGreen
• Begin to calibrate R D Agenda and co-operative
  mechanisms necessary for sustained environmental
  genomics research agenda for Canada

30
Canadian Genomics Research in the Environment
Network- A Concept
31
Pursuit of Future Environment Canada Green
Genomics Partnerships

• NIEeS Genomes and the Environment UK Workshop
  2005
• SETAC Session on Omics November 2005(Maryland)
• SETAC Pelleston Workshop on Toxicogenomics(Michi
  gan)
• OECD Toxicogenomics Workshop November 2005
• Environment Canada CANGREEN workshop 2006?

32
Potential for Future International Green
Genomics R D Alliances

• USEPA Environmental Genomics Program
• US Department of Energy Genomes to Life Program
• UK BBSRC / NERC Environmental Genomics Program

33
USEPA Genomics Research and Development 2003-04
Computational Toxicology
34
Research Focus Areas
Chemical transformation Metabonomics Molecular
indicators Dose metrics Toxicity pathways Systems
biology Computational infrastructure
35
USDOE GENOMES TO LIFE PROGRAM
36
Scientific Goals of USDOE Genomes to Life Program

• Identify the protein machines that carry out
  critical life functions
• Characterize the gene regulatory networks that
  control these machines
• Explore the functional repertoire of complex
  microbial communities in their natural
  environments as a prelude to their use against
  DOE priorities
• Develop the computational capabilities to
  integrate and understand this data

37
Developing UK-Canada Linkages in Genomics

• Brassica genomics collaborative agreement
  between Canadian and UK genomic networks
  (BBSRC/NRC/AAFC) joint fund for travel, meetings
  and short exchanges for post-doctoral researchers
• Stem cells major UK mission to Canada and the
  USA in 2003 (Canadian stem cells network
  currently advising BBSRC on establishing similar
  activity in the UK
• Environment Canada BBSRC / NERC / NIEeS Future
  Collaboration???

38
FOR FURTHER CONTACT

• Terry McIntyre Ph.D. P.Ag.
• Chief Environmental Biotechnology
• Applications Division
• Technology and Industry Branch
• Environment Canada
• 18th Floor, P.V.M.,
• 351 St. Joseph Blvd.,
• Gatineau, Quebec, CANADA
• Tel (8l9) 994-1105
• e-mail terry.mcintyre_at_ec.gc.ca