industry day living foundries darpa
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Living Foundries
Alicia Jackson
Program Manager, DARPA
Living Foundries Industry Day
Arlington VA
June 28, 2011
8/23/2011 1Approved for Public Release, Distribution Unlimited
DARPA
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The question that all DARPA programs must answer: Is it game changing and will it have lasting impact on DOD and the warfighter?
Prevent technological surprise and Create technological surprise
• Sponsor revolutionary, high-payoff research
• Driven by the Program Managers
• Capabilities/Mission focused
• Diverse performers—looking for the best people with the best ideas
• No peer review
• Driven by quantitative milestones
• Flexible, rapid review and contracting
Heilmeier's Catechism
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1. What are you trying to do? What problem are you trying to solve? Articulate your objectives using absolutely no jargon.
2. How is it done today, and what are the limits of current practice?
3. What's new in your approach and why do you think it will be successful?
4. Who cares?
5. If you're successful, what difference will it make?
6. What are the risks and the payoffs?
7. How much will it cost?
8. How long will it take?
9. What are the midterm and final "exams" to check for success?
Living Foundries
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Living Foundries: The Vision
Chemicals
Fuels
Pharma
Molecules
“cell-like” factory
Sugar
Natural gas
Cellulose
PET
Coal
Custom, distributed, on-demand manufacturing
DNA instructions
Polymers
Catalysts
Electronic/ optical materials
Multi-cellular constructs
Self-repairing systems
“cell-free” systems
Image adapted from: Vickers et al., Nature Chemical Biology, 2010 and Keasling, Science, 2010
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1.00E+11
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Complexity (# genes inserted/modified)
1010
1011
109
108
107
106
105
104
103
Eff
ort
(to
tal
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yrs
to
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*yr]
yeastminimal bacterium
Engineering biology today is a time and money intensive process
DARPA annual budget
We’re just scratching the surface of what’s possible
Where Living Foundries will take us
genome rewritecomplex genetic circuits
metabolic engineering
SOA
SOA: ad hoc, empirical, expensive process
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Goal: hierarchical engineering
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Smallsystems
Large systems
Many iterations
No iteration
Application
Itera
te >
20x
Standardization and modularity of genetic parts and chasses
Abstraction of genetic function to manage complexity
Decoupling of design and fabrication
New approach: decouple design from fabrication through design rules and standardized parts
• Natural parts don’t work as expected outside of native environment
• Not all parts exist
• Design rules are unknown
• No reliable design tools
7 yrs (SOA)
Time (months)
Transform
Transform 3 wks
Coupled Design/Fabrication
~105 attempts
4 m
os
DNACoupled design and fabrication +20x
Parts/Devices
Design tools
Fabrication
Test/Debug
Application
Program cells in a high-level language and compile to genetic code
Standardized, well-characterized parts and devices that are CAD friendly
Automated synthesis and assembly of DNA in standardized cell chassis
Quick, high-throughput identification and quantification of the cell state
Example of a possible approach
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What is needed for Living Foundries
An open and accessible platform for engineering biology
• Interoperable tools for design, modeling and fabrication
• Well-characterized, standardized and orthogonal genetic parts
• Scalable, low-cost, high-fidelity DNA synthesis processes with rapid turn-times
• Test platforms and chassis that readily and predictably integrate new genetic designs
• Locate failures and characterize the whole cell state
Design tools that span from high-level description to fabrication in cells
Modular genetic parts that allow a combination of systems to be
designed and reproducibly assembled
Rapid construction, evolution and manipulation of genetic designs
Routine system characterization and debugging that informs the design cycle
What is needed Technical Challenges
Accelerate the biological design, build, test cycle and expand the complexity of designs that can be built.
This list is not comprehensive: Additional/alternative areas of research and development may be proposed
Structure of Living Foundries
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Anticipated BAA #1Advanced Tools and
Capabilities
Anticipated BAA #2:Living Foundries Challenge
Demonstrations 24 Months
ATC BAA
BAA
Demonstrate tools and platform capabilities
Integrate tools and platform
capabilities in full demonstration
Demonstrate capability to build multiple complex functionalities in a “cell-like” systems
Outcome:
• Interoperable design tools
• New, modular genetic parts, regulators, and circuits
• Standardized test platforms, cell-like systems and chassis
• Low cost, rapid DNA synthesis
• Quantitative, high throughput characterization and debugging
Outcome:
Demonstrate capability to build multiple complex functionalities,
on demand, in a “cell-like” system
Integrate the tools and capabilities around a series of challenge demonstrations to prove-out the Living Foundries goal of rapid biological design and engineering
Tools and capabilities to accelerate the biological design, build, test cycle and expand the complexity of designs that can be built.
Proof of concept
BAA #1: Example areas of interest
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(1) Design tools that span from high-level description to synthetic circuit modeling to
automated fabrication in cells, i.e. interoperable tools and databases for design,
modeling, and fabrication
(2) Modular genetic parts, regulators, devices, and circuits (and the new methods
to develop and refine these) that allow a combination of systems to be designed
and reproducibly assembled increasing the efficiency, sophistication, and scale of
possible designs.
(3) Rapid construction, editing and manipulation of genetic designs, including low
cost DNA synthesis and assembly techniques, facile modification and manipulation of
genetic designs into a system/chassis, and designs engineered to readily translate
between different systems/chassis
(4) Well understood test platforms, ‘cell-like’ systems and chassis that readily integrate
new genetic designs in a predictable fashion
(5) Routine system characterization and debugging of synthetic gene networks that
feeds back and informs the design cycle
Accelerate the biological design, build, test cycle and
expand the complexity of designs that can be built.
This list is not comprehensive: Additional/alternative areas of research and development may be proposed
Proposed Program Scope & Structure
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• Each proposal may address one or more areas of interest
• Proposals must address how the need for future integration will inform the design and development of tools/capabilities from their conception
Simultaneously developing multiple interrelated tools, technologies
and/or methodologies in close concert is one way to address this requirement
• Proposals must ensure tight coupling between any proposed design tool development and experimental work
• Proposals must include a proof-of-concept to demonstrate utility to the Living Foundries goals and to aid teaming for BAA#2
• Successful proposals will consist of a multidisciplinary team with expertise both inside and outside of the biological sciences
A successful proposal will address:
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1. Why is the specific tool/capability proposed important and what problem does it solve? Be quantitative.
2. What is the impact? Be quantitative. If successful, by how much will each tool/capability speed the biological design, build, test cycle and/or expand the complexity of designs that can be built?
3. What is the end goal and how does this compare against the current state of the art? Include quantitative metrics.
4. What is the new technical idea behind the proposed tool/capability and why can it succeed now? Provide examples of recent scientific advances that will enable success.
5. How will each specific tool/capability be developed to ensure its ability to integrate with and support other tools/capabilities?
6. What is the proposed proof-of-concept to be demonstrated by the end of Phase I to demonstrate the utility of the proposed tools/capabilities to the Living Foundries goals?
7. What is your approach/strategy to mitigate any potential safety/security risks during technology development?
8. Looking ahead to the challenge demonstrations in BAA #2—if successful, what specific new target applications will be possible that cannot be achieved today?
How will you take Living Foundries from vision to reality?
Living Foundries
Living Foundries: Impact Example
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Transform
Transform
DNA synth/ assemblyIdentify /modify potential genes and assemble potential pathways +20x
1 1 2 3 4 Time (months)
Design cycle time At least 1 order of magnitude decrease in design cycle time
>100x
Complexity (#genes)
>100x
Evaluation Criteria
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1. Overall Scientific and Technical Merit
2. Potential Contribution and Relevance to the DARPA Mission
3. Proposer’s Capabilities and/or Related Experience
4. Realism of Proposed Schedule
5. Cost Realism
Other Considerations
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Interoperability
DARPA expects its investment in design tools and databases developed under the Living Foundries program to be multiplied many-fold by adoption and improvement by researchers throughout the US. To facilitate interoperability, the goal is to have all applicable design tools and databases developed under the ATC program be compatible with Synthetic Biology Open Language (SBOL) core data model.
Bio-Safety and Security
Proposers must ensure that all methods and demonstrations of capability comply with any national guidance for manipulation of genes and organisms and meet all criteria for biological safety and security
Proposals should address any potential bio-safety/security issues that the development of the proposed tools/capabilities might pose. They should include a discussion of approaches and strategies to manage, mitigate and monitor these risks during technology development.