DARPA-BAA-14-49_FINAL_CMO_08-12-14.docx

DARPA-BAA-14-49, Biological Robustness in Complex Settings (BRICS)

Broad Agency Announcement

Biological Robustness in Complex Settings (BRICS)

BIOLOGICAL TECHNOLOGIES OFFICE

DARPA-BAA-14-49

DATE

TABLE OF CONTENTS

Part One: Overview Information

· Federal Agency Name – Defense Advanced Research Projects Agency (DARPA), Biological Technologies Office

· Funding Opportunity Title – Biological Robustness in Complex Settings (BRICS)

· Announcement Type – Initial Announcement

· Funding Opportunity Number – DARPA-BAA-14-49

· Catalog of Federal Domestic Assistance Numbers (CFDA) - 12.910 Research and Technology Development

· Dates

· Posting Date (Date Posted to FBO and/or Grants.gov – to be completed by CMO)

· Proposer’s Day Date: Thursday, August 21, 2014

· Full Program Abstract Due Date: Tuesday, September 23, 2014

· Full Program Proposal Due Date: Tuesday, December 2, 2014

· Advanced Study Abstract Due Date: Tuesday, September 30, 2014

· Advanced Study Proposal Due Date: Tuesday, January 20, 2015

· BAA Closing Date (maximum of 180 days after date posted on https://www.fbo.gov website) Concise description of the funding opportunity - The development of techniques and tools to rapidly sequence, synthesize, and manipulate genetic material has led to the rapidly maturing discipline of synthetic biology. The potential applications enabled by this field include efficient on-demand bio-production of novel drugs, fuels and coatings; engineered microbes able to optimize human health or prevent or treat disease; and bio-based sensors, tags, or tracking systems. To date, work in synthetic biology has focused primarily on manipulating individual species of domesticated organisms. These species tend to be fragile, requiring precise environmental controls to survive, and unstable, subject to losing their engineered advantages through genetic attrition or recombination. The costs of maintaining required environmental controls and detecting and compensating for genetic alterations are substantial. If applications such as those highlighted above are to come to fruition, methods to increase the biological robustness and stability of engineered organisms must be achieved while maintaining or enhancing assurances of safety. The Biological Robustness in Complex Settings (BRICS) program will develop the fundamental understanding and component technologies to engineer biosystems that maintain their functional value in environments less stringently controlled than those in which these systems are today cultivated, eventually enabling the safe transition of synthetic biological systems from well-defined laboratory environments into more complex settings where they can achieve greater biomedical, industrial, and strategic potential. While this program will support the development of technologies that would be prerequisite to the safe application of engineered biological systems in the full range of environments in which the DoD has interests, all work performed in this program will occur in controlled laboratory settings.

· Total amount of money to be awarded - It is anticipated that approximately $42.5M will be awarded across the Full Program and Advanced Studies track, as described within this BAA. The Full Program track will receive the majority of BRICS program funding. The actual amount of resources available under this BAA will depend on the quality of proposals received and availability of funds.

· Anticipated individual awards - Multiple awards are anticipated.

· Anticipated funding type - 6.1 and 6.2

· Types of instruments that may be awarded - Procurement contract and other transactions.

· Any cost sharing requirements – None.

· Agency contact Dr. Justin Gallivan, Program Manager The BAA Coordinator for this effort may be reached at:

DARPA-BAA-14-49@darpa.mil

DARPA/BTO

ATTN: DARPA-BAA-14-49

675 North Randolph Street Arlington, VA 22203-2114

Part Two: Full Text of Announcement

1. Funding Opportunity Description The Defense Advanced Research Projects Agency often selects its research efforts through the Broad Agency Announcement (BAA) process. This BAA is being issued, and any resultant selection will be made, using procedures under Federal Acquisition Regulation (FAR) 35.016 and the Department of Defense Grant and Agreement Regulatory System (DoDGARS) Part 22 for Grants and Cooperative Agreements. Any negotiations and/or awards will use procedures under FAR 15.4, Contract Pricing, as specified in the BAA (including DoDGARS Part 22 for Grants and Cooperative Agreements). Proposals received as a result of this BAA shall be evaluated in accordance with evaluation criteria specified herein through a scientific review process.

DARPA BAAs are posted on the Federal Business Opportunities (FedBizOpps) website, https://www.fbo.gov, and, as applicable, the Grants.gov website at http://www.grants.gov. The following information is for those wishing to respond to the BAA.

The development of techniques and tools to rapidly sequence, synthesize, and manipulate genetic material has led to the rapidly maturing discipline of synthetic biology. The potential applications enabled by this field include efficient on-demand bio-production of novel drugs, fuels and coatings; engineered microbes able to optimize human health or prevent or treat disease; and bio-based sensors, tags, or tracking systems. To date, work in synthetic biology has focused primarily on manipulating individual species of domesticated organisms. These species tend to be fragile, requiring precise environmental controls to survive, and unstable, subject to losing their engineered advantages through genetic attrition or recombination. As a result, many engineered biological systems require resource-intensive provision of precise temperature control, well-defined rich media, pre-sterilized environments and strongly selective conditions (e.g., the presence of antibiotics) to ensure survival and reduce competition from other microorganisms.

The economic and strategic practicality of harnessing engineered biological systems for the full range of capabilities they embody would be greatly enhanced if these systems could operate reliably and safely under less stringent conditions. Indeed, for many potential applications in synthetic biology it is impractical to precisely control the environment or predict how the environment will change. For example, engineered probiotic bacteria have the potential to improve human health, but to be successful they must function reliably and safely in the gastrointestinal tract, where diet and endogenous microbiota vary among individuals.

If applications such as those highlighted above are to come to fruition in relevant concepts of operations, methods to increase the biological robustness of engineered organisms must be achieved. Robustness in this context can be described as the ability of an organism or consortium of organisms to safely and reliably perform a particular task while being subjected to perturbations.

Through the Biological Robustness in Complex Settings (BRICS) program, DARPA is soliciting innovative research proposals to develop the necessary fundamental understanding and component technologies to create robust engineered biological systems. It is expected that technology developed in the BRICS program will enable the safe transition of synthetic biological systems from stringently controlled laboratory environments to more complex settings. The BRICS portfolio will consist of a set of programs, of which this is the first, that aim to elucidate the design principles of engineering robust biological consortia and apply this fundamental understanding towards specific DoD applications. This announcement calls for the development of generalizable approaches that may be ultimately integrated into a complex biological system. DARPA anticipates a second BAA comprising specific challenge scenarios that require the integration of capabilities developed within this program.

Proposals submitted in response to DARPA-BAA-14-49 should include innovative approaches that enable revolutionary advances in science. Proposals that will produce only evolutionary improvements to the existing state of practice will be deemed “non-responsive” to this announcement.

Biosafety and Security The goal of BRICS is to develop foundational technologies that will set the field of synthetic biology on a path towards the eventual safe use of microbes that maintain their functional value in environments less stringently controlled and more complex than those in which they are cultivated today. While this program will support the development of technologies that would be prerequisite to the safe application of engineered biological systems in non-laboratory settings—including, for example, the human gastrointestinal tract or complex mechanical or chemical environments where bio-based sensors or films might have utility—all work performed in this program will occur in controlled laboratory settings. Proposals that include efforts to manipulate or study genetically modified organisms in any context not completely insulated from the natural environment will be deemed “non-responsive” to this announcement.

Proposers must ensure and demonstrate throughout the program that all methods and demonstrations of capability comply with national guidance for manipulation of genes and organisms and follow all guidance for biological safety and biosecurity. Proposals should address any potential safety/security issues that the development of the proposed tools/capabilities might pose and include a discussion of approaches and strategies to manage, mitigate and monitor these risks during technology development. In addition, all proposed efforts must meet any applicable regulations designed to protect human health and the environment promulgated by the Environmental Protection Agency, the Food and Drug Administration, the Department of Agriculture, the Department of Health and Human Services, and any other cognizant agencies within the federal government. Proposers must also comply with any state or municipal regulations or ordinances governing biotechnology practices.

1.1. Program Overview

1.1.1 Introduction

The DARPA BRICS program seeks to engineer biological systems that are robust to environmental and genetic impacts. This BAA consists of two proposal tracks: (1) Full Program Proposals and (2) Advanced Study Proposals.

Full Program Proposals will be required to address all of the critical elements deemed necessary to achieve the end-program objective of engineering a robust, stable, and safe biosystem as described in Section 1.1.2. Due to the increased scope of work required under this track, successful proposers will most likely consist of multi-disciplinary collaborative teams.

Advanced Study Proposals should be focused efforts that address specific challenges in designing robust biological communities, as described in Section 1.1.3 below. While narrower in scope, these efforts provide the infrastructure necessary to characterize, develop, and scale processes developed under the BRICS Full Program Proposal track.

Please read the instructions in the following sections carefully, as the schedule and requirements differ for the two program tracks.

1.1.2 Full Program Proposals

DARPA has identified three key areas of innovation that are necessary to ensure the safe and reliable use of synthetic biology in complex environments. Proposals are sought that address all three of the Technical Areas outlined in the following sections. To mitigate technical risk, the three Technical Areas must be addressed independently and in parallel (i.e., success of any one Technical Area should not depend on the successful completion of other Technical Areas). However, proposers should work to ensure that the technologies developed to complete each task can be integrated during the anticipated subsequent integration challenge. The technical feasibility of integration will be a consideration during proposal evaluations. Proposals to develop technologies that represent ad hoc solutions to a single problem, or that are incompatible with technologies and analytical tools commonly used in synthetic biology, are specifically discouraged. Though not strictly required, it is expected that proposals will involve multidisciplinary teams that include expertise from both the traditional synthetic biology community, as well as areas that have not typically engaged in this area (e.g., process control and systems engineers, population biologists, and ecologists).

The three technical areas aim to (1) optimize the functional reliability of engineered organisms in stochastic settings, i.e., robustness narrowly defined; (2) preserve the genetic integrity of engineered systems, i.e., stability; and (3) develop methods to rigorously control the growth and proliferation of engineered organisms under non-laboratory conditions, i.e., safety.

TA-1: Robustness The fitness of laboratory strains commonly used in synthetic biology is low relative to strains found in nature. The reduced fitness of domesticated microbes, such as E. coli K12, has many causes, but a major factor is that these organisms have been selected to grow in monoculture, often under narrowly defined conditions of temperature and nutrient availability. In contrast, natural microbes tend to live in diverse communities comprising many species that share the metabolic load of biosynthetic pathways, collaborate to manage changes in the environment, and protect the community from invasive species. Therefore, one approach to engineering synthetic biological systems that can function robustly in complex environments is to design synthetic communities consisting of multiple organisms that reinforce the viability of the entire group and allow the synthetic system to persist in the face of environmental perturbations.

For this technical area, proposers are asked to develop the necessary technology to create a functional, multi-species, synthetic microbial community. The community must be engineered to perform a function, which is at the discretion of the proposers but must require essential contributions from all species of the microbial community. Examples of engineered functions include, but are not limited to, the biosynthesis of a specific molecule or the ability to sense and respond to a substance in the environment. The complexity of community composition and function should increase as the BRICS program progresses.

TA-2: Stability The inherent tendency for biological systems to evolve presents a major challenge to the goal of using engineered organisms in changing environments. To realize this goal, the genetic stability of engineered organisms will need to be markedly improved, not only so they remain stable with respect to their engineered function but also to prevent the transfer of engineered functions to organisms in the surrounding ecosystem. A multifaceted approach will be necessary to stabilize the genetics of synthetic strains. First, the rate at which mutations accumulate in the synthetic population will need to be reduced. Second, approaches to mitigate the effects of any residual mutation rate on the engineered function will need to be developed, such that loss of an engineered trait does not improve fitness. Finally, methods to genetically isolate the synthetic strains from their surroundings will be needed to manage environmental impact.

For this technical area, proposers are asked to develop the necessary technology to create engineered microbes with basal mutation rates that are reduced 100-fold relative to a wild-type strain; are genetically stable with respect to some engineered function (e.g., biosynthesis of a specific molecule and/or environmental sense-and-respond); and do not participate in events that allow genetic traits to be shared between species, such as horizontal gene transfer (HGT). Proposals that rely on strategies that would be technically difficult or cost-prohibitive to implement in the field or at-scale are discouraged.

TA-3: Safety To consider using engineered microbial systems for biomedical (e.g., “probiotic”) or other non-laboratory applications, it is imperative that there be mechanisms to guard against unanticipated impacts or unintended use.

There are many examples of complicated, non-biological engineered systems designed to operate robustly within changing conditions but also able to shut down or respond in other appropriate ways when relevant parameters are exceeded. As part of their strategy for ensuring safety, such systems rely on established principles of process control, through such capacities as the ability to sense and respond to perturbations in predefined ways. Many are also designed with redundant systems in addition to backup systems.

In this task area, proposers are asked to develop analogous methods for engineered biological systems. Specifically, proposers are asked to develop methods to detect when the performance of an engineered biological system is compromised, and to prevent the growth or proliferation of the system in an autonomous way. In designing these mechanisms, proposers should consider potential causes of dysfunction that could be encountered in non-laboratory ecosystems. The resulting technology will include systems that are triggered due to auto-regulation of cell function and intercellular monitoring of the function and structure of the community.

1.1.3 Advanced Study Proposals

Separate from the Full Program Proposals described in section 1.1.2, DARPA anticipates funding multiple Advanced Study Proposals that enhance and facilitate the development, integration, or use of technologies being developed under the BRICS program. Advanced Study proposals must address one or more of the following topic areas.

AS-1. Tools for genetic engineering of undomesticated microbes The domesticated microbes that are the typical chasses of synthetic biology are not well suited to growth outside of controlled laboratory conditions. A potential solution to improving the robustness of synthetic strains is to engineer desired functions into undomesticated strains rather than domesticated strains. This approach is challenged by the lack of molecular tools available for manipulating the genetics of undomesticated organisms. We seek proposals that develop methods to design and build genetic pathways that will function in undomesticated species from a wide range of phyla (prokaryotic or eukaryotic), including but not limited to: techniques for strain transformation, building and testing of genetic elements for regulation of gene expression, and methods for culturing and manipulating undomesticated multi-species communities.

AS-2. Analytical tools for high-resolution characterization of in vivo communities To monitor the structure and function of engineered multi-species consortia it is essential to have analytical tools that can provide quantitative measures of gene expression, protein expression, and metabolite concentrations determined across time and space. We seek proposals to develop analytical tools that allow the simultaneous measurement of relevant parameters, including but not limited to concentrations of mRNAs, proteins, and small molecules, within multi-species consortia. Techniques that can be used to assess the spatiotemporal dynamics of gene expression networks across a community are of particular interest.

AS-3. Experimental platforms for the study of multi-species communities Culturing platforms for ex vivo multi-species communities with defined 3-dimensional structures are needed to improve the understanding of interspecies communication, as well as to provide a convenient model for testing hypotheses. We seek proposals to develop appropriate generalizable culture substrates that provide control over community structure and composition and support the growth of both prokaryotic and eukaryotic cells. Proposed technologies should also be compatible with analytical techniques used to periodically sample gene expression across the community, as well as time-lapse imaging techniques.

AS-4. Robust gene circuits To enhance the complexity of engineered gene networks that can be reliably built and integrated in synthetic microbial communities, it is important to develop methods that improve the robustness of engineered gene circuits. We seek proposals that develop methods to efficiently design, build, and test genetic parts that improve the robustness of synthetic gene circuits, including, but not limited to: insulation devices, negative feedback amplifiers, mechanisms to access endogenous ribosome stores, and low-concentration protein circuits. Methods for engineering degeneracy and redundancy into synthetic circuits are particularly desired. Proposed technologies must be generalizable and scalable, such that they are readily incorporated into a variety of chassis organisms.

AS-5. Theoretical approaches to understanding multi-species communities The ability to predict the long-term dynamics of community structure and function is an important tool in the design of synthetic microbial consortia. We seek proposals that develop new models to explain the dynamic interactions that occur both among the cells of the community, as well as between the community as a whole and its environment. Proposed technologies could include computational tools for analyzing and understanding large amounts of biological data obtained from microbial communities grown in complex settings.

AS-6. Approaches to reduce the robustness of the genetic code The degeneracy of the “universal” genetic code allows for the tolerance of point mutations because most random mutations result in either conservative or silent changes with respect to the expressed protein sequence. Efforts to redesign the genetic code such that there is an increased chance that point mutations will be deleterious at the protein level may increase the likelihood that an organism’s genome is resistant to mutation. We seek proposals that develop methods for reducing the robustness of the universal genetic code, thereby increasing the preservation of engineered functions in populations of synthetic microbes, while minimizing the effects of genetic mutation.

1.2 Schedule and Deliverables

The proposed period of performance for Full Program Proposals should not exceed 30 months. The proposed period of performance for Advanced Study Proposals should not exceed 24 months.

1.2.1 Full Program Proposals

The execution of Full Program Proposals should be organized into three phases, with the first phase (Phase 1) expected to last no more than 6 months. Funding for Phase 2 and Phase 3 is contingent on meeting the milestones in the previous phases. Phase 1 should focus on the development of capabilities and include a proof-of-concept demonstration that aligns to the overall BRICS objectives. The remainder of the effort should focus on refining the tools and capabilities to demonstrate the ability to translate across multiple platforms and systems in preparation for a follow-on integration program. Note that work performed under this BAA should not be confined to one particular challenge demonstration or application that results in a one-off capability; tools and capabilities proposed should enable the ability to tackle a broad array of challenges. Each proposal should include a discussion of how the proposed tools/capabilities advance the vision of the BRICS program, a detailed evaluation of the state-of-the-art for the respective tool, technology or methodology, a plan for the safe and responsible development of the proposed tools/capabilities, a notional integration plan, as well as quantitative performance and evaluation metrics.

TA-1: Robustness Phase 1 (6 months)

· Develop a scalable approach to engineer multispecies consortia of organisms. In this phase, it is essential to demonstrate in practice that the approach can organize two or more microbial species into a community with stable and predictable dynamics. This phase is designed to allow performers to quickly test several strategies; it is recommended that proposals include alternative approaches to achieving this capability.

· Identify a single approach to move forward with. The chosen approach must be generalizable and scalable such that it can be used to build communities of arbitrary size, complexity, and function.

Phase 2 (12 months)

· Increase the size of the engineered community to a minimum of five species.

· Engineer the community to perform a proposed function. As stated above, the engineered function must depend on essential contributions of all members of the engineered microbial community; i.e., a single biosynthetic strain in co-culture with four other strains does not satisfy this challenge.

Phase 3 (12 months)

· Produce an engineered community that satisfies the criteria above and maintains its function when grown in the presence of environmental insults. Such insults could include, but are not limited to: temperature variation and shifts in nutrient concentration.

· Demonstrate that the community is resistant to invasion by competitive species (e.g., other microbes, phage/viruses) without resorting to strategies that would be difficult to implement at-scale or outside of the laboratory (i.e., endowing all species with resistance to an antibiotic and exogenously providing that antibiotic as a selection against competitors is not a scalable solution).

Proposals should describe in technical detail approach(es) to generating self-organizing multi-species communities, the specific engineered function that the community will perform, and the type of environmental insults that will be used to demonstrate the robustness of the community viability and function. Proposals should suggest appropriate milestones and deliverables for the end of each Phase of the program.

The deliverables for the end of Phase 3 must include a synthetic multi-cellular community with the following characteristics:

· Capable of self-organization (i.e., not merely a co-culture)

· Resistant to invasion by competitive species in the environment

· Able to carry out an engineered function that depends on contributions from multiple community members (e.g., biosynthesis of valuable molecule and/or environmental sense and response)

· Able to maintain viability and engineered function across a range of growth conditions TA-2: Stability Phase 1 (6 months)

· Develop simple prototypes to demonstrate the utility of proposed approaches to engineer stable systems. As in TA-1, proposers are encouraged to explore several strategies during this phase.

· Identify a single approach to accomplishing each of the desired capabilities: a basal mutation rate that is reduced by 100-fold, functional robustness, and resistance to horizontal gene transfer (HGT).

Phase 2 (12 months)

· Expand the capabilities developed in Phase 1 for each aspect of genetic stability (100-fold reduced basal mutation rate, functional robustness, and resistance to HGT).

· Integrate the three stability traits into a single biological system that exhibits a synthetic function (e.g., biosynthesis of a specific molecule, or environmental sense-and-respond system) Phase 3 (12 months)

· Demonstrate that the synthetic biological system developed in Phase 2 is stable with respect to function when grown under a range of stressful conditions for ≥1000 generations in the presence of heterologous genetic material.

The resulting biological system can be a single strain or a multicellular community. However, the technologies developed must be compatible with eventual use in multi-species communities, as described for TA-1. Conversely, approaches that require multiple cell types (and, therefore, do not work in monoculture) are acceptable. For example, methods to ensure that community members exhibit coordinated evolution to maintain an engineered function would potentially address parts of this challenge. The engineered function of the biological system used in this technical area is at the discretion of the proposer, and it may differ from the function engineered into the microbial community for TA-1.

Proposals should describe in technical detail the approaches to generating functionally stable biological systems that do not participate in HGT, as well as the type of environmental insults that will be used to demonstrate these capabilities in Phase 3. Proposals should suggest appropriate milestones and deliverables for the end of each Phase of the program. The deliverables for the end of Phase 3 must include a synthetic biological system that:

· Shows a 100-fold reduction in basal mutation rate

· Is resistant to horizontal gene transfer

· Is less fit when the engineered function is lost TA-3: Safety Phase 1 (6 months)

· Design and develop autonomous sensing mechanisms for at least three intracellular properties of cell function (including native and synthetic functions) to detect when the performance of an engineered biological system is compromised.

· Design and develop autonomous sensing mechanisms for at least three key properties of the community to detect when the structure of an engineered multi-species community is compromised.

Phase 2 (12 months)

· Develop an autonomous mechanism that prevents the growth of synthetic system upon loss of a community interaction.

· Develop an autonomous method that connects the growth of the synthetic community to the output of the system, such that growth is arrested upon diminished performance.

Phase 3 (12 months)

· Develop an autonomous intracellular mechanism that allows the function or output of one cell type (producer) to be monitored by a second cell type (sensor). If the sensor detects reduced output from the producer, the sensor initiates a response that inhibits growth of the producer.

· Demonstrate an autonomous biological system that actively monitors at least three properties of a microbial community (e.g., product output, presence/absence of a community member, relative population density). If one or more of the properties deviates from a prescribed set-point/range, the system shall terminate the growth of the entire multicellular population within 2 hours, and prevent additional growth for at least 7 days.

As in TA-2, the engineered function of the biological system used in this technical area is at the discretion of the proposer, and it may differ from the function engineered into the microbial community in either TA-1 or TA-2. It is recommended that proposers not take risks in designing this aspect of the system, as the focus for this challenge should be on engineering safety mechanisms.

Proposals should describe in technical detail the approaches to generating sensors of cell and community function and structure, the mechanisms that will be used to prevent growth in the event of reduced performance, and the anticipated kinetics and persistence of autonomous systems. Proposals should suggest appropriate milestones and deliverables for the end of each Phase of the program. The deliverables for the end of Phase 3 must include a synthetic biological system with the following attributes:

· Intracellular growth inhibitory mechanism upon reduced performance of an engineered function (e.g., the production of biosynthetic product, or a loss of community interaction)

· Intercellular surveillance mechanisms that monitor the function of the community and prevent the growth of neighboring cells upon diminished performance.

Collaboration Collaborative efforts/teaming are encouraged if the proposed tools/capabilities require a team to ensure successful execution. Any teams should be sized according to the scale of the technical effort proposed and expertise required. A teaming website has been established at https://safe.sysplan.com/BRICS/ to facilitate the formation of teaming arrangements between interested parties. Specific content, communications, networking, and team formation are the sole responsibility of the proposer. Neither DARPA nor the Department of Defense (DoD) endorses the destination web site or the information and organizations contained therein, nor does DARPA or the DoD exercise any responsibility at the destination. This website is provided consistent with the stated purpose of this BAA.

1.2.2 Advanced Study Proposals

The execution of Advanced Studies should be organized into two phases lasting 12 months each. Phase 1 should focus on the development of desired capabilities in the relevant areas outlined in Section 1.1.2 Advanced Studies and include a proof-of-concept demonstration. Funding for Phase 2 is contingent on meeting the milestones of Phase 1. The remainder of the effort should focus on refining the tools and capabilities to demonstrate appropriate robustness and the ability to translate across multiple platforms and systems. Work performed as part of Advanced Studies should not result in a one-off capability; tools and capabilities proposed should enable the ability to tackle a broad array of challenges. Each proposal should include a discussion of how the proposed tools/capabilities advance the vision of the BRICS program, a detailed evaluation of the state-of-the-art for the respective tool, technology or methodology, a plan for the safe and responsible development of the proposed tools/capabilities, as well as quantitative performance and evaluation metrics.

2. Award Information Multiple awards are possible. The amount of resources made available under this BAA will depend on the quality of the proposals received and the availability of funds.

The Government reserves the right to select for negotiation all, some, one, or none of the proposals received in response to this solicitation, and to make awards without discussions with proposers. The Government also reserves the right to conduct discussions if it is later determined to be necessary. If warranted, portions of resulting awards may be segregated into pre-priced options. Additionally, DARPA reserves the right to accept proposals in their entirety or to select only portions of proposals for award. In the event that DARPA desires to award only portions of a proposal, negotiations may be opened with that proposer. The Government reserves the right to fund proposals in phases with options for continued work at the end of one or more of the phases.

Awards under this BAA will be made to proposers on the basis of the evaluation criteria listed below (see section labeled “Application Review Information”, Sec. 5.), and program balance to provide overall value to the Government. The Government reserves the right to request any additional, necessary documentation once it makes the award instrument determination. Such additional information may include but is not limited to Representations and Certifications. The Government reserves the right to remove proposers from award consideration should the parties fail to reach agreement on award terms, conditions and cost/price within a reasonable time or the proposer fails to timely provide requested additional information. Proposals identified for negotiation may result in a procurement contract, grant, cooperative agreement, or other transaction depending upon the nature of the work proposed, the required degree of interaction between parties, whether or not the research is classified as Fundamental Research, and other factors.

In all cases, the Government contracting officer shall have sole discretion to select award instrument type and to negotiate all instrument terms and conditions with selectees. Proposers are advised that if they propose grants or cooperative agreements, DARPA may select other award instruments, as it deems appropriate. DARPA will apply publication or other restrictions, as necessary, if it determines that the research resulting from the proposed effort will present a high likelihood of disclosing performance characteristics of military systems or manufacturing technologies that are unique and critical to defense. Any award resulting from such a determination will include a requirement for DARPA permission before publishing any information or results on the program. For more information on publication restrictions, see the section below on Fundamental Research.

2.1 Fundamental Research

It is DoD policy that the publication of products of fundamental research will remain unrestricted to the maximum extent possible. National Security Decision Directive (NSDD) 189 established the national policy for controlling the flow of scientific, technical, and engineering information produced in federally funded fundamental research at colleges, universities, and laboratories. The Directive defines fundamental research as follows:

“Fundamental research means basic or applied research in science and engineering, the results of which ordinarily are published and shared broadly within the scientific community, as distinguished from proprietary research and from industrial development, design, production, and product utilization the results of which ordinarily are restricted for proprietary or national security reasons.”

As of the date of publication of this BAA, the Government expects that program goals as described herein may be met by proposers intending to perform fundamental research. The Government does not anticipate applying publication restrictions of any kind to individual awards for Fundamental Research that may result from this BAA. Notwithstanding this statement of expectation, the Government is not prohibited from considering and selecting research proposals that, while perhaps not qualifying as fundamental research under the foregoing definition, still meet the BAA criteria for submissions. If proposals are selected for award that offer other than a fundamental research solution, the Government will either work with the proposer to modify the proposed statement of work to bring the research back into line with fundamental research or else the proposer will agree to restrictions in order to receive an award.

Proposers should indicate in their proposal whether they believe the scope of the research included in their proposal is fundamental or not. While proposers should clearly explain the intended results of their research, the Government shall have sole discretion to select award instrument type and to negotiate all instrument terms and conditions with selectees. Appropriate clauses will be included in resultant awards for non-fundamental research to prescribe publication requirements and other restrictions, as appropriate.

For certain research projects, it may be possible that although the research being performed by the prime contractor is restricted research, a subcontractor may be conducting contracted fundamental research. In those cases, it is the prime contractor’s responsibility to explain in their proposal why its subcontractor’s effort is contracted fundamental research.

The following statement or similar provision will be incorporated into any resultant non-fundamental research procurement contract or other transaction:

There shall be no dissemination or publication, except within and between the contractor and any subcontractors, of information developed under this contract or contained in the reports to be furnished pursuant to this contract without prior written approval of DARPA’s Public Release Center (DARPA/PRC). All technical reports will be given proper review by appropriate authority to determine which Distribution Statement is to be applied prior to the initial distribution of these reports by the contractor. With regard to subcontractor proposals for Contracted Fundamental Research, papers resulting from unclassified contracted fundamental research are exempt from prepublication controls and this review requirement, pursuant to DoD Instruction 5230.27 dated October 6, 1987.

When submitting material for written approval for open publication, the contractor/awardee must submit a request for public release to the PRC and include the following information: (1) Document Information: document title, document author, short plain-language description of technology discussed in the material (approx. 30 words), number of pages (or minutes of video) and document type (e.g., briefing, report, abstract, article, or paper); (2) Event Information: event type (conference, principal investigator meeting, article or paper), event date, desired date for DARPA's approval; (3) DARPA Sponsor: DARPA Program Manager, DARPA office, and contract number; and (4) Contractor/Awardee's Information: POC name, e-mail and phone. Allow four weeks for processing; due dates under four weeks require a justification. Unusual electronic file formats may require additional processing time. Requests may be sent either by-mail to PRC@darpa.mil or via 675 North Randolph Street, Arlington VA 22203-2114, telephone (571) 218-4235. Refer to the following for link for information about DARPA’s public release process: http://www.darpa.mil/NewsEvents/Public_Release_Center/Public_Release_Center.aspx.

3. Eligibility Information All responsible sources capable of satisfying the Government’s needs may submit a proposal that shall be considered by DARPA.

3.1 Eligible Applicants

3.1.1 Federally Funded Research and Development Centers (FFRDCs) and Government Entities FFRDCs and Government entities (e.g., Government/National laboratories, military educational institutions, etc.) are subject to applicable direct competition limitations and cannot propose to this BAA in any capacity unless they meet the following conditions: (1) FFRDCs must clearly demonstrate that the proposed work is not otherwise available from the private sector (2) FFRDCs must provide a letter on official letterhead from their sponsoring organization citing the specific authority establishing their eligibility to propose to Government solicitations and compete with industry, and their compliance with the associated FFRDC sponsor agreement and terms and conditions. This information is required for FFRDCs proposing to be prime contractors or subcontractors. Government entities must clearly demonstrate that the work is not otherwise available from the private sector and provide written documentation citing the specific statutory authority and contractual authority, if relevant, establishing their ability to propose to Government solicitations. At the present time, DARPA does not consider 15 U.S.C.§ 3710a to be sufficient legal authority to show eligibility. While 10 U.S.C. § 2539b may be the appropriate statutory starting point for some entities, specific supporting regulatory guidance, together with evidence of agency approval, will still be required to fully establish eligibility. DARPA will consider FFRDC eligibility submissions on a case-by-case basis; however, the burden to prove eligibility for all team members rests solely with the proposer.

3.1.2 Non-US Organizations

Non-U.S. organizations are/or individuals may participate to the extent that such participants comply with any necessary nondisclosure agreements, security regulations, export control laws, and other governing statutes applicable under the circumstances. See Section 4.2 “Security and Proprietary Issues” regarding the proposers capabilities to perform research and development at the classification level they propose.

3.2 Procurement Integrity, Standards of Conduct, Ethical Considerations, and Organizational Conflicts of Interest Current federal employees are prohibited from participating in particular matters involving conflicting financial, employment, and representational interests (18 U.S.C.§ 203, 205, and 208). Once the proposals have been received, and prior to the start of proposal evaluations, the Government will assess potential conflicts of interest and will promptly notify the Proposer if any appear to exist. The Government assessment does NOT affect, offset, or mitigate the proposer’s responsibility to give full notice and planned mitigation for all potential organizational conflicts, as discussed below.

Without prior approval or a waiver from the DARPA Director, in accordance with FAR 9.503, a contractor cannot simultaneously provide scientific, engineering, technical assistance (SETA) or similar support and also be a technical performer. As part of the proposal submission, all members of the proposed team (prime proposers, proposed subcontractors, and consultants) must affirm whether they (their organizations and individual team members) are providing SETA or similar support to any DARPA technical office(s) through an active contract or subcontract. All affirmations must state which office(s) the proposer, subcontractor, consultant, or individual supports and identify the prime contract number(s). All facts relevant to the existence or potential existence of organizational conflicts of interest (FAR 9.5) must be disclosed. The disclosure must include a description of the action the proposer has taken or proposes to take to avoid, neutralize, or mitigate such conflict. If in the sole opinion of the Government after full consideration of the circumstances, a proposal fails to fully disclose potential conflicts of interest and/or any identified conflict situation cannot be effectively mitigated, the proposal will be rejected without technical evaluation and withdrawn from further consideration for award.

If a prospective Proposer believes a conflict of interest exists or may exist (whether organizational or otherwise) or has questions on what constitutes a conflict of interest, the proposer should send his/her contact information and a summary of the potential conflict to the DARPA-BAA-14-49@darpa.mil before time and effort are expended in preparing a proposal and mitigation plan.

3.3 Cost Sharing/Matching

Cost sharing is not required; however, it will be carefully considered where there is an applicable statutory condition relating to the selected funding instrument (e.g., for any Other Transactions under the authority of 10 U.S.C.§2371). Cost sharing is encouraged where there is a reasonable probability of a potential commercial application related to the proposed research and development effort.

3.4 Other Eligibility Requirements

3.4.1 Collaborative Efforts

Collaborative efforts/teaming are encouraged if the proposed tools/capabilities require a team to ensure successful execution. Any teams should be sized according to the scale of the technical effort proposed and expertise required. A teaming website has been established at https://safe.sysplan.com/BRICS/ to facilitate the formation of teaming arrangements between interested parties. Specific content, communications, networking, and team formation are the sole responsibility of the proposer. Neither DARPA nor the Department of Defense (DoD) endorses the destination web site or the information and organizations contained therein, nor does DARPA or the DoD exercise any responsibility at the destination. This website is provided consistent with the stated purpose of this BAA.

4. Application and Submission Information

4.1 Address to Request Application Package

This solicitation contains all information required to submit a proposal. No additional forms, kits, or other materials are needed. This notice, with the classified addendum, constitutes the total solicitation. No additional information is available, except as provided at https://www.fbo.gov, nor will a formal Request for Proposal (RFP) or additional solicitation regarding this announcement be issued. Requests for the same will be disregarded.

4.2. Content and Form of Application Submission

4.2.1 Security Issues

The Government anticipates proposals submitted under this BAA will be unclassified. However, if a proposal is submitted as “Classified National Security Information” as defined by Executive Order 13526, then the information must be appropriately and conspicuously marked with the proposed classification level and declassification date. Submissions requiring DARPA to make a final classification determination shall be marked as follows:

CLASSIFICATION DETERMINATION PENDING. Protect as though classified (insert the recommended classification level: (e.g., Top Secret, Secret or Confidential) Security classification guidance and direction via a Security Classification Guide (SCG) and/or DD Form 254, “DoD Contract Security Classification Specification,” will not be provided at this time, since DARPA is soliciting ideas only. After reviewing the incoming proposals, if a determination is made that the award instrument may result in access to classified information, a SCG and/or DD Form 254 will be issued and attached as part of the award.

4.2.2 Proprietary Data

All proposals containing proprietary data should have the cover page and each page containing proprietary data clearly marked as containing proprietary data. It is the proposer’s responsibility to clearly define to the Government what is considered proprietary data.

Proposers must have existing and…