1000 Molecules Proposers Day

Alicia Jackson
DARPA/MTO

July 24, 2013

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Engineering Biology

Design and construct genetic pathways, networks

and systems to harness the powerful synthetic and
functional capabilities of biology.

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What You Need to Know

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Proposals Due September 17, 2013

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Read the BAA

Vision
Requirements
Proposal Instructions
Evaluation Criteria
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Vision

Enable transformative and currently inaccessible

projects across chemicals, materials, sensing
capabilities and therapeutics

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Requirements

Key Technical Components and Capabilitiesp. 8

Teaming and Partnershipspp. 11 and 12
Intermediate Milestonespp. 14 and 15

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Proposal Instructions

Follow Them

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Evaluation Criteria: p. 47 of BAA

Overall Scientific and Technical Merit

Potential Contribution and Relevance to the DARPA Mission

Proposers Capabilities and/or Related Experience

Cost Realism

Realism of Proposed Schedule

Plans and Capability to Accomplish Technology Transition

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If you have Questions: DARPA-BAA-13-37@darpa.mil

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Living Foundries: 1000 Molecules

The Details

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Building a new technology base to enable transformative

applications
Living Foundries: ATCG
New tools to enable rapid
engineering of biology

Living Foundries: 1000 Molecules

Foundries
Enable scale and rapid
prototyping of genetic designs
never before accessible

Demo New Capability

1000 Molecules
1000 new chemical building
blocks for new materials

100x faster DBT cycle for

engineering biology

Enable Impossible Projects

...

IMPACT:
Open up new avenues for innovation
Enable access/new entrants
Engage and Seed industrial/academic partnerships
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Fundamental shift in
chemical/materials industry

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Petro-materials paradigm dominates today

Inputs

Commodity
Chemicals

Materials

Products

MATERIEL/INFRASTRUCTURE

FIELD GEAR

Todays materials are built from a limited set of building blocks

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Petrochemical starting molecules are limited

Olefins: alkenes including those

with 2, 3, 4, and >4 carbons

US Petroleum
Refinery Yield

Special Naphthas
(0.2%)
Oils bp 401 F
(0.7%)

Petroleum
Coke (5.1%)

Naphtha bp 401
F (1.2%)

Kerosenetype Jet Fuel

(8.8%)

Liquefied Refinery
Gases (3.7%)

Distillate Fuel
Oil (27.0%)

Still Gas (4.1%)

Aromatics: conjugated,
planar, cyclic compounds

Finished Motor
Gasoline (42.0%)
42 US Gallons

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Biology provides a far richer palette of starting points

Olefins: alkenes including those

Creatine

with 2, 3, 4, and >4 carbons

Coniine

Ladderanes

Fluorocarbons

Biotin

Adenine

Phosphatidylinositol
Farnesene

Aromatics: conjugated,
planar, cyclic compounds

1,3-Propanediol

Heme
Shikimic acid

Riboflavin Caprolactam
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New materials produced using engineered biosystems

can enhance DoD capabilities
Inputs
Inherently Flexible,
Adaptable Platform
Carbon sources:
Corn, Sugarcane,
Biomass, CO2,
Nat Gas, etc.

Commodity
Chemicals

Materials

Expanded
Chemical Palette

New
Materials
with new
properties

Products
Speed DoD
Technology
Development

>103 increase in
intermediates

(from 10s to 10,000s)

Chemical Factories:
Yeast, Algae, new
exotic microorganisms
and in-vitro systems

New chemical structures and functions enable new avenues for innovation
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Engineering biology could enable the next advance

Biology

Petroleum & Natural Gas

Engineering Biology
Genetically
Encoded Materials

Inflection
point

Inflection
point

2040

Source: Morgan Stanley Research

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Infrastructure: Scaled, rapid prototyping of genetic designs

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Key elements/expectations
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.

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Key elements/expectations (2)

GOAL: Scalable and accessible technology base

Successful proposals:
Advanced process design utilizing best industrial
manufacturing practices,
Integration and modularization of component technologies,
Identification of driving technical and scientific challenges.

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Key tech components/challenges

1. Design Innovation: Enable

forward engineering of new systems

2. Scalable, Automated Construction:

Parallelized construction of combinatorial

genetic designs

Novel biosynthetic pathway prediction

Large-scale DNA construction

Gene cluster discovery

Optimized genetic chassis

Chemical structure prediction

Genome-scale, parallel editing tools

Tools for design and control of

complex networked systems

Flexible across organisms/designs

4. Integrated Feedback: Harness

massive data generation to inform future

design

3. Design Evaluation: Massively

parallel test and QC of designs

Analysis of all data, including failure modes

Machine learning and data mining algorithms
Generate design rules
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Integrated, highthroughput detection and

analysis
Automated QC of parts,
assembly, and integration
Validation/verification of
engineered systems
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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
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Teaming and management expectations

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

Commitment: Expect significant time commitment from core team

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1000 Molecules
Overview/Purpose: Provides a measure of capabilities

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
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1000 Molecules challenge areas

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 nonnatural amino acids into products
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Task Area 2: Demonstration of capabilities

Challenge Area 3: Prototyping of
novel materials from new chemistries

Challenge Area 1: Rapid, improved

prototyping of known molecules

Sequence defined, nonnatural polymers

Super absorbent materials Polyitaconic acid

Insecticides Spinocyn

New nanomaterials

Coating/Fibers Muconic acid

Novel Catalysts

Natural Products Artmesinin

Hybrid materials systems

Phase I
18 mos

Phase II
18 mos

Phase III
24 mos

FY15

FY18

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

Challenge Area 2: Prototyping of

known, but currently inaccessible,
molecules
Electro/Optical molecules
Anti-corrosive coatings
Thermopolymers
High-strength polymers

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Anticipated program structure

Task Area 2

Task Area 1
6 mos

Phase I

Phase II

Phase III

18 mos

18 mos

24 mos

FY14

FY18

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
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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
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initial proposals to TA1
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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?
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Task Area 2 proposals must address: (contd)

(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 teams previous accomplishments and work in closely

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

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Anticipated program milestones

TA Phase
TA1
TA2
Phase I
TA2
Phase II

TA2
Phase III

Program
End

Timeline

Milestones

Up to 6 mo

Project plan
Proof of concept (option)
Initiate infrastructure (option)

Up to 18 mo

Produce 10 target molecules (Areas 1/2)

Demonstrate infrastructure capabilities (2 proposerdefined milestones)

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)

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)

Up to 60 mo

Produce 350 target molecules, including at least

45 previously inaccessible target molecules (Area 2)
10 novel target molecules (Area 3)
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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
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Advanced Studies
TA1
6 mos

TA2
Phase I

Phase II

Phase III

18 mos

18 mos

24 mos

FY14

FY18

Advanced Studies

FY14

Phase I

Phase II

12 mos

12 mos
FY16

Duration: maximum of 24 months and

should consist of 2 phases, each no longer
than 12 months.

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.
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Key points
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

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
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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

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www.darpa.mil

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