DARPA Living Foundries 1000 molecules Proposers Day slides

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1000 Molecules Proposers’ Day

Alicia Jackson DARPA/MTO

July 24, 2013

Approved for Public Release, Distribution Unlimited 2

Engineering Biology

Design and construct genetic pathways, networks and systems to harness the powerful synthetic and

functional capabilities of biology.


What You Need to Know


Proposals Due September 17, 2013


Vision

Requirements

Proposal Instructions

Evaluation Criteria

Read the BAA


Enable transformative and currently inaccessible projects across chemicals, materials, sensing

capabilities and therapeutics

Vision


Key Technical Components and Capabilities—p. 8

Teaming and Partnerships—pp. 11 and 12

Intermediate Milestones—pp. 14 and 15

Requirements


Follow Them

Proposal Instructions


• Overall Scientific and Technical Merit

• Potential Contribution and Relevance to the DARPA Mission

• Proposer’s Capabilities and/or Related Experience

• Cost Realism

• Realism of Proposed Schedule

• Plans and Capability to Accomplish Technology Transition

Evaluation Criteria: p. 47 of BAA


If you have Questions: [email protected]

mailto:[email protected]


Living Foundries: 1000 Molecules

The Details

12

Building a new technology base to enable transformative applications

Living Foundries: ATCG

Foundries

Demo New Capability

New tools to enable rapid engineering of biology

Enable scale and rapid prototyping of genetic designs

never before accessible

1000 Molecules 1000 new chemical building

blocks for new materials 100x faster DBT cycle for engineering biology

Fundamental shift in chemical/materials industry

. . . Enable Impossible Projects

Living Foundries: 1000 Molecules

IMPACT:

Engage and Seed industrial/academic partnerships

Open up new avenues for innovation Enable access/new entrants



Petro-materials paradigm dominates today

Inputs Commodity Chemicals

Materials Products

MATERIEL/INFRASTRUCTURE

FIELD GEAR

Today’s materials are built from a limited set of building blocks

14

Petrochemical starting molecules are limited

Finished Motor Gasoline (42.0%)

Distillate Fuel Oil (27.0%)

Kerosene-type Jet Fuel

(8.8%)

Petroleum Coke (5.1%)

Still Gas (4.1%)

Liquefied Refinery Gases (3.7%)

Naphtha – bp ≤ 401º F (1.2%)

Oils – bp ≥ 401º F (0.7%)

Special Naphthas (0.2%)

US Petroleum Refinery Yield

42 US Gallons

Olefins: alkenes including those with 2, 3, 4, and >4 carbons

Aromatics: conjugated, planar, cyclic compounds



Biology provides a far richer palette of starting points

Olefins: alkenes including those with 2, 3, 4, and >4 carbons

Aromatics: conjugated, planar, cyclic compounds

Caprolactam

Ladderanes Fluorocarbons

1,3-Propanediol

Farnesene

Riboflavin

Phosphatidylinositol

Heme

Creatine Coniine

Shikimic acid

Adenine Biotin


New materials produced using engineered biosystems can enhance DoD capabilities

New chemical structures and functions enable new avenues for innovation

Materials Commodity Chemicals

Products Products

Speed DoD Technology

Development

Commodity Chemicals

>103 increase in intermediates

(from 10’s to 10,000’s)

Expanded Chemical Palette

Inputs Inputs

Carbon sources: Corn, Sugarcane,

Biomass, CO2, Nat Gas, etc.

Chemical Factories: Yeast, Algae, new

exotic microorganisms and in-vitro systems

Inherently Flexible, Adaptable Platform

Materials

New Materials with new properties


Engineering biology could enable the next advance

Biology Petroleum & Natural Gas Engineering Biology

Inflection point

2040

Inflection point

Source: Morgan Stanley Research

Genetically Encoded Materials

18

Infrastructure: Scaled, rapid prototyping of genetic designs


GOAL: Scalable and accessible technology base

• Bridge the gap from initial, laboratory-level, proof-of-concept experimentation to industrial pilot production.

• Enable scale and sophistication of engineering orders of magnitude > SOA

• Automated, integrated processes across design, fabrication, testing, and analysis.


Key elements/expectations

GOAL: Scalable and accessible technology base


Key elements/expectations (2)

Successful proposals:

• Advanced process design utilizing best industrial

manufacturing practices,

• Integration and modularization of component technologies,

• Identification of driving technical and scientific challenges.

Key tech components/challenges

1. Design Innovation: Enable forward engineering of new systems

• Novel biosynthetic pathway prediction

• Gene cluster discovery

• Chemical structure prediction

• Tools for design and control of complex networked systems

2. Scalable, Automated Construction: Parallelized construction of combinatorial genetic designs

• Large-scale DNA construction

• Optimized genetic chassis

• Genome-scale, parallel editing tools

• Flexible across organisms/designs

3. Design Evaluation: Massively parallel test and QC of designs

• Integrated, high-throughput detection and analysis

• Automated QC of parts, assembly, and integration

• Validation/verification of engineered systems

4. Integrated Feedback: Harness massive data generation to inform future design

• Analysis of all data, including failure modes

• Machine learning and data mining algorithms

• Generate design rules Approved for Public Release, Distribution Unlimited 21


Meta-elements/expectations

Beyond the technology and process infrastructure

Infrastructure should:

• Be applicable to addressing diverse applications beyond biosynthesis of new molecules e.g. synthetic biological circuits and networks, creation of libraries, recoding and refactoring of genomes, etc.

• Readily import, test, and integrate new methods and tech

• Engage and partner with end users, technology developers and infrastructure providers


Teams • Mix of Institutions/Partners – academic, non-profit, and industrial

collaborations

• Multidisciplinary - computer science, engineering, automation, industrial process development, chemistry/chemical engineering, biological sciences, etc

• Core team members and researchers are expected to be co-located with the centralized rapid design and prototyping infrastructure maximize interactions and project focus.

Leadership • Teams may be led by industrial, academic, or non-profit entities • Leadership Team should have significant experience and expertise in:

• Directing operations and technology development, • Leading large and diverse teams with both academic and industrial

partners, and • Industrial process design

Teaming and management expectations

Commitment: Expect significant time commitment from core team

Overview/Purpose: Provides a measure of capabilities


1000 Molecules

• Generate >350 unique molecules demonstrating a breadth of structural and functional diversity

• >1000 unique molecules in total generated across all facilities

• Demonstrate infrastructure capabilities in • throughput, • rapid product generation, and • platform flexibility and generalizability

Across numerous designs, pathways, and products

3 Challenge Areas: 1. Rapid, improved prototyping of known molecules.

• Known biosynthetic pathways. • Includes: molecules previously synthesized biologically and natural products. • Demonstrate improved production (e.g., yield, cost, purity, etc.) relative to

state-of-the-art production methods by using a biosynthetic route.

2. Prototyping of known, but currently inaccessible, molecules. • Not routinely synthesized biologically • Includes synthetic pathways constructed from multiple, unique organisms. • Of particular interest to DARPA: molecules that are currently very difficult,

impossible, or prohibitively expensive to synthesize chemically.

3. Prototyping of novel molecules. •Effectively unattainable through synthetic chemistry and cannot be synthesized using existing biological chemistry.

•Examples: novel enzymes to enable inaccessible pathways, incorporation of novel elements from the periodic table, or high-efficiency incorporation of non-natural amino acids into products


1000 Molecules challenge areas

Task Area 2: Demonstration of capabilities

Phase I Phase II

FY15 18 mos 18 mos

Phase III 24 mos

FY18

Challenge Area 1: Rapid, improved prototyping of known molecules Super absorbent materials – Polyitaconic acid

Insecticides – Spinocyn

Coating/Fibers – Muconic acid

Natural Products – Artmesinin

Challenge Area 3: Prototyping of novel materials from new chemistries Sequence defined, nonnatural polymers –

New nanomaterials –

Novel Catalysts –

Hybrid materials systems

Electro/Optical molecules– Anti-corrosive coatings – Thermopolymers – High-strength polymers –

Challenge Area 2: Prototyping of known, but currently inaccessible, molecules


• Phase 1: >10 molecules from Areas 1 or 2

• Phase 2: >60 molecules, including >15 molecules from Area 2.

• Phase 3: >10 molecules from Area 3 and > 200 additional molecules from Challenge Areas 1 and 2.

>350 unique molecules total by end of Phase III


Anticipated program structure

Phase I Phase II

FY14 18 mos 18 mos

Phase III

24 mos

FY18

Task Area 1

6 mos

Task Area 2

Task Area 1 (TA1): Initial infrastructure and technical design exploration • Infrastructure plan and technical path are refined

• Culminates in a technical report detailing the proposed technical approach, physical capabilities, and management structure.

Task Area 2 (TA2): Require centers to develop/demonstrate capabilities Consists of three phases:

• Phase 1: “pressure test” - produce at least 10 molecules by the end of Phase 1.

• Phase 2 - Produce > 60 molecules, including > 15 known, but currently inaccessible, molecules (i.e. Challenge Area 2).

• Phase 3 – Produce > 10 completely novel molecules (i.e. Challenge Area 3) and > 200 additional molecules from Challenge Areas 1 and 2.

Performers that complete Task Area 1 may submit proposals to Task Area 2


Proposing to Task Area 1: Design and study phase

Provide: Brief and concise overview of anticipated project plan and approach to meet the goals and milestones of the Living Foundries: 1000 Molecules program. Task Area 1 Study: Identify anticipated technical elements, milestones and metrics to be refined and/or generated during the Task Area 1 design and study phase of the program. Technical Rationale and Approach: Outline of the anticipated technical approach and plan for Task Area 2, including how the Task Area 1 study work fits into the overall project plan.

Technical approach and plan must address: • Description of the proposed infrastructure to be developed • Overview of and timeline for the technical approach • Description of and justification for the types of molecules that will be targeted

during each phase of Task Area 2 • Initial steps/proof-of-concept experiments toward developing the proposed

infrastructure • Anticipated academic and industrial partners

DARPA requires proposers to submit all initial proposals to TA1


Task Area 2 proposals must address:

(1) Complete Technical approach and plan that addresses the following:

• Description of proposed infrastructure

• Overview of the technical approach, milestones, and timeline both related to infrastructure capabilities and to the 1000 molecules goal

• Major Technical Risk Elements

• Description of and justification for the types/classes of molecules that will be targeted during each phase of TA2

• How the proposed infrastructure can be used to address applications beyond the biosynthesis of new molecules.

• Proposed intermediate and end-of-project demos and proofs-of-concept

(2) Program Plan: A plan with clear timelines, milestones and risks identified for demonstrating the functional capabilities and performance of the proposed rapid design and prototyping facility as a whole, as well as for individual components

(3) Teaming and Management plan

(5) Tech Transition Plan: How the infrastructure facility will maintain viability following cessation of DARPA funding?


Task Area 2 proposals must address: (cont’d)

(6) SOW • A general description of the objective • A brief and concise description of the approach • Identification of the primary organization responsible for task execution • The completion criteria for each task/activity - a product, event or milestone that defines

its completion; • Define all deliverables (reporting, data, reports, software, etc.) to be provided to the

Government in support of the proposed research tasks/activities; and • An estimate of cost

(7) Discussion of proposer team’s previous accomplishments and work in closely related research areas.

(8) Description of the facilities and capabilities that would be used for the proposed effort.


TA Phase Timeline Milestones

TA1 Up to 6 mo • Project plan • Proof of concept (option) • Initiate infrastructure (option)

TA2 Phase I Up to 18 mo

• Produce 10 target molecules (Areas 1/2) • Demonstrate infrastructure capabilities (2 proposer-

defined milestones)

TA2 Phase II Up to 18 mo

• Produce 60 target molecules, including at least • 15 previously inaccessible target molecules (Area 2)

• Further demonstration of infrastructure capabilities (2 proposer-defined milestones)

TA2 Phase III Up to 24 mo

• Produce 200 target molecules, including at least • 30 previously inaccessible target molecules (Area 2) • 10 novel target molecules (Area 3)

• Further demonstration of infrastructure capabilities (3 proposer-defined milestones)

Program End Up to 60 mo

• Produce 350 target molecules, including at least • 45 previously inaccessible target molecules (Area 2) • 10 novel target molecules (Area 3)

Anticipated program milestones


Comprehensive Efforts vs. Advanced Studies

2 categories of proposals for this solicitation:

(1) Comprehensive proposals (2) Advanced Studies: Innovative component technologies • Markedly improve the performance of the rapid design and

prototyping infrastructure • Can be readily automated, parallelized, scaled-up, and/or

utilized in reduced reaction volumes • Limited to a maximum of 24 months in length • Only a limited number is expected be funded

The Government strongly prefers an integrated approach to systematically address all program goals in their entirety


• Advanced studies: address one or more novel component technologies targeted as part of infrastructure development.

• Clearly indicate Advanced Studies proposal submission on title page • Explain the relevance of the work to the overall program goals, as well as propose

detailed objectives and quantitative metrics.

• Groups proposing advanced studies are encouraged to identify teams proposing rapid design and prototyping centers that may be able to leverage the tools and technologies resulting from such a study.

Advanced Studies

Phase I Phase II

FY14 18 mos 18 mos

Phase III

24 mos

FY18

TA1

6 mos

TA2

Phase I Phase II

FY14 12 mos

Advanced Studies

12 mos FY16

Duration: maximum of 24 months and should consist of 2 phases, each no longer than 12 months.


Proposers should focus on 3 aspects:

• Designing and demonstrating a rapid design and prototyping infrastructure that will enable a radical improvement in capabilities over SOA

• Outlining the technical approach(es) to be pursued to meet the infrastructure and DARPA 1000 goals

• Identifying and justifying the molecules and chemical building blocks proposed for each DARPA 1000 Challenge Area

Key points

The Government expects to fund several types of rapid design and prototyping infrastructure, spanning a range of approaches, foci, and users

All proposed infrastructure should be generalizable in that it can address a

range of designs, pathways, organisms/systems and/or products


Key dates

BAA Released

10 July 2013

BAA Process and Proposal Preparation/Submission Overview Webinar

31 July 2013

Proposals for TA1 and Advanced Studies Due

17 Sept 2013

Estimated Start date for TA1 and Advanced Studies

17 March 2014

Note: BAA will remain open until 21 Oct 2014

www.darpa.mil


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DARPA Living Foundries 1000 molecules Proposers Day slides

Education