Industry Day Living Foundries DARPA

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Industry Day Living Foundries DARPA

  1. 1. Living Foundries Alicia Jackson Program Manager, DARPA Living Foundries Industry Day Arlington VA June 28, 20118/23/2011 Approved for Public Release, Distribution Unlimited 1
  2. 2. DARPAPrevent 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 contractingThe question that all DARPA programs must answer: Is it game changing and will it have lasting impact on DOD and the warfighter?8/23/2011 Approved for Public Release, Distribution Unlimited 2
  3. 3. Heilmeiers Catechism1. 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. Whats new in your approach and why do you think it will be successful?4. Who cares?5. If youre 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?8/23/2011 Approved for Public Release, Distribution Unlimited 3
  4. 4. Living Foundries8/23/2011 Approved for Public Release, Distribution Unlimited 4
  5. 5. Living Foundries: The Vision Polymers DNA Catalysts instructions Electronic/ optical Cellulose materials Natural gas Chemicals Sugar Molecules Fuels PET Pharma Coal “cell-like” Multi-cellular factory constructs Self-repairing Custom, distributed, systems on-demand manufacturing “cell-free” systemsImage adapted from:Vickers et al., Nature Chemical Biology, 2010 and Keasling, Science, 2010 8/23/2011 Approved for Public Release, Distribution Unlimited 5
  6. 6. We’re just scratching the surface of what’s possible Engineering biology today is a time and money intensive process minimal bacterium yeast 11 1.00E+11 10 Effort (total $ * yrs to develop) [$*yr] 10 1.00E+10 10 DARPA annual budget 1.00E+09 109 1.00E+08 108 SOA 1.00E+07 107 1.00E+06 106 5 1.00E+05 10 Where Living Foundries will take us 4 1.00E+04 10 metabolic engineering complex genetic circuits genome rewrite 1.00E+03 103 1 1 10 10 100 100 1,000 1,000 10,000 10,000 100,000 100,000 Complexity (# genes inserted/modified)8/23/2011 Approved for Public Release, Distribution Unlimited 6
  7. 7. New approach: decouple design from fabrication through design rules and standardized partsSOA: ad hoc, empirical, Goal: hierarchical engineering expensive process Large systems Standardization and modularity (def band-detect (s lo hi) (and (> s lo) (< s hi)))) of genetic parts and chasses (let ((s (diffuse (aTc) 0.8 0.05))) (green (band-detect Abstraction of genetic function s 0.2 1))) Small to manage complexity Many iterations systems X No Decoupling of design and iteration fabrication Application Application Example of a possible approach Program cells in a high-level language Coupled Design tools and compile to genetic codeIterate >20x Design/Fabrication Standardized, well-characterized parts 4 mos Parts/Devices and devices that are CAD friendly Automated synthesis and assembly of ~105 attempts Fabrication DNA in standardized cell chassis 7 yrs (SOA) Quick, high-throughput identification Test/Debug and quantification of the cell state • Natural parts don’t work as expected outside of native environment Coupled design and fabrication DNA Transform+20x • Not all parts exist • Design rules are unknown Transform 3 wks • No reliable design tools Time (months) 8/23/2011 7 Approved for Public Release, Distribution Unlimited
  8. 8. What is needed for Living Foundries Accelerate the biological design, build, test cycle and expand the complexity of designs that can be built. What is needed Technical Challenges Design tools that span from high-level • Interoperable tools for design, modeling description to fabrication in cells and fabrication • Well-characterized, standardized and Modular genetic parts that allow a orthogonal genetic parts combination of systems to be • Scalable, low-cost, high-fidelity DNA designed and reproducibly assembled synthesis processes with rapid turn-times • Test platforms and chassis that readily and Rapid construction, evolution and predictably integrate new genetic designs manipulation of genetic designs • Locate failures and characterize the whole cell state Routine system characterization and This list is not comprehensive: Additional/alternative debugging that informs the design cycle areas of research and development may be proposed An open and accessible platform for engineering biology8/23/2011 Approved for Public Release, Distribution Unlimited 8
  9. 9. Structure of Living Foundries Anticipated BAA #1 Advanced Tools and Demonstrate tools Capabilities and platform capabilities Outcome: Tools and capabilities to• Interoperable design tools accelerate the biological• New, modular genetic parts, regulators, and circuits design, build, test cycle• Standardized test platforms, Proof of concept and expand the ATC BAA cell-like systems and chassis complexity of designs• Low cost, rapid DNA synthesis that can be built.• Quantitative, high throughput Integrate tools characterization and and platform debugging capabilities in full demonstration Anticipated BAA #2: Living Foundries Challenge Demonstrations 24 Months Outcome: BAA DemonstrateDemonstrate capability to buildmultiple complex functionalities, capability to build on demand, in a “cell-like” multiple complex system functionalities in a “cell-like” systems Integrate the tools and capabilities around a series of challenge demonstrations to prove-out the Living Foundries goal of rapid biological design and engineering8/23/2011 Approved for Public Release, Distribution Unlimited 9
  10. 10. BAA #1: Example areas of interest Accelerate the biological design, build, test cycle and expand the complexity of designs that can be built.(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 cycleThis list is not comprehensive: Additional/alternative areas of research and development may be proposed8/23/2011 Approved for Public Release, Distribution Unlimited 10
  11. 11. Proposed Program Scope & Structure• 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 sciences8/23/2011 Approved for Public Release, Distribution Unlimited 11
  12. 12. A successful proposal will address: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?8/23/2011 Approved for Public Release, Distribution Unlimited 12
  13. 13. Living Foundries: Impact Example >100x >100x Living Foundries Complexity (#genes) DNA synth/Design Identify /modify potential genes and assemble potential pathways assembly Transform +20xcycletime Transform At least 1 order of magnitude decrease in design cycle time 1 2 1 3 4 Time (months)8/23/2011 Approved for Public Release, Distribution Unlimited 13
  14. 14. Evaluation Criteria 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 Realism8/23/2011 Approved for Public Release, Distribution Unlimited 14
  15. 15. Other ConsiderationsInteroperabilityDARPA expects its investment in design tools and databases developed under the Living Foundriesprogram 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 developedunder the ATC program be compatible with Synthetic Biology Open Language (SBOL) core data model.Bio-Safety and SecurityProposers must ensure that all methods and demonstrations of capability comply with any nationalguidance for manipulation of genes and organisms and meet all criteria for biological safety and securityProposals should address any potential bio-safety/security issues that the development of the proposedtools/capabilities might pose. They should include a discussion of approaches and strategies tomanage, mitigate and monitor these risks during technology development.8/23/2011 Approved for Public Release, Distribution Unlimited 15

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