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OPPORTUNITY – National Science Foundation (NSF) Dear Colleague Letter: Rules of Life (RoL)

OPPORTUNITY – National Science Foundation (NSF) Dear Colleague Letter: Rules of Life (RoL)

NSF 18-071

Dear Colleague Letter: Rules of Life (RoL): Design and Engineering of Synthetic Cells and Cell Components (DESYN-C3)

April 18, 2018

Dear Colleagues:

NSF seeks proposals that jump-start the de novo design of complex, synthetic biological components and cells. This DCL intends to engage scientists and engineers in the application of Design-Build-Test-Learn and experiment-modeling cycles to create synthetic cells. It is anticipated that the research will lead to new rules relevant for cell metabolism, epigenetics, interaction networks, and organelle function; molecular components and organelles of cells; and strategies for the design and synthesis of cells.


Synthetic cellular biomanufacturing has the potential to improve the production of fuels, chemicals, functional biomaterials, and human therapeutics, and to enhance bioremediation and ecological engineering in a profound and sustainable fashion. New therapies and cell-based products depend critically on the development of robust, reliable and reproducible biomanufacturing technologies. The design of these technologies has been enabled by basic science research on biomolecular design and synthesis aimed at understanding biological function, the development and application of chemistry for probing cellular function, and the identification of causal relationships in biological systems (e.g. genotype/phenotype, structure/function). Effective utilization of these science and engineering developments will enable biosystem designers to avoid the constraints of existing biological regulatory systems to create novel, optimized biosynthetic reaction systems that are adaptive and responsive to external stimuli.

The de novo design of synthetic cells will require the convergence of traditional chemistry and chemical engineering activities (chemical synthesis and self-assembly, process synthesis and control, reaction engineering, mass transport, separations) with diverse other research areas, including control theory, synthetic biology, systems biology, biomaterials science, biochemistry, molecular structure, dynamics, and modeling, chemical biology, and bioorganic and bioinorganic chemistry. This effort will also require advanced nanomanufacturing technologies, such as DNA-enabled nanofabrication, to produce the subsystems (motors, pumps, constrained volume reactors, actuators) that comprise the synthetic cells.

This Dear Colleague Letter (DCL) describes an initial effort to expand and test our current understanding through the design of synthetic cell components (ribosomes, mitochondria, membranes, regulators, molecular machines, etc.) and molecular probes, and their synthesis and integration into “pseudo-cells” that efficiently convert raw materials to useful products. This effort resonates with the high priority placed by the Directorate for Engineering on advanced biomanufacturing and by the Directorate for Mathematics and Physical Sciences on understanding the fundamental science that underlies life processes, and it complements the NSF Ten Big Ideas of Understanding the Rules of Life and Growing Convergent Research.

The NSF Divisions of Chemical, Bioengineering, Environmental and Transport Systems (CBET), Civil, Mechanical and Manufacturing Innovation (CMMI) in the Directorate of Engineering (ENG), and Chemistry (CHE) and Materials Research (DMR) in the Directorate of Mathematical and Physical Sciences (MPS) seek to support activities that include Conferences, EArly-Concept Grants for Exploratory Research (EAGER), and Research Advanced by Interdisciplinary Science and Engineering (RAISE) grants.


Prior to submitting EAGER or RAISE proposals, interested principal investigators (PIs) must prepare research concept outlines. Note, conference proposals (see the NSF Proposal & Award Policies & Procedures Guide (PAPPG), Chapter II.E.7) do not require the submission of a research concept outline. The research concept outlines must include clear statements as to why this project is appropriate for either EAGER funding (see PAPPG, Chapter II.E.2) or RAISE funding (see PAPPG, Chapter II.E.3). Research concept outlines must also include the compelling research challenge being addressed and its direct relevance to synthetic cell design. The research concept outline should address the current state of the research challenge and describe an integrated strategy for addressing that challenge.

The research concept outlines must not exceed two pages and must comply with standard proposal margin and spacing requirements (see PAPPG, Chapter II.B.2). They must contain the following information:

  • Title of the DESYN-C3 research.
  • Description of and justification for the proposed research.
  • Names, and the Departmental and Institutional affiliations of researchers.
  • Contact information of the researchers (email and phone number).
  • An estimated budget amount (including both direct and indirect costs). A detailed budget is not required for the research concept outline. See the Summary of the Opportunity section below for budget limitations for EAGER and RAISE proposals.

The research concept outline should be emailed to and must be submitted by May 17, 2018. Research concept outlines that either do not provide the requested information or do not comply with formatting guidelines may not be reviewed.


PIs submitting research concept outlines that effectively address how self-sustaining (not necessarily self-replicating) “pseudo-cells” exhibiting specific functions can be effectively designed and implemented may be invited to submit a full proposal. Decisions on full proposal submissions will be based on research efforts that could lead to major advances in the design of effective cellular subsystems.

Please note that an invitation to submit a full proposal is not an indication that the proposal will be funded. Full proposals will undergo further internal review by the participating divisions before funding decisions are made. The number of research concept outlines invited to submit a full proposal are subject to the quality of concepts received and available funding (up to 20 may be invited). All funding decisions will be made during fiscal year 2018 (FY 2018).


NSF will review proposals that propose activities in the following areas:

  • Conferences that engage the research communities in identifying the minimal composition (structurally and functionally) of a functional “pseudo-cell”: Conference awards will provide up to one year of support for projects that do not exceed $100,000 in total. Proposals must include the prefix “RoL: Conference: DESYN-C3” in front of the title. There is no deadline for submission of these proposals; however, to be considered for FY 2018 support, proposals should be submitted by June 15, 2018. Conference proposals should follow the guidance in PAPPG, Chapter II.E.7.
  • EAGER projects to develop and test the functionality of integrated, natural or synthetic multi-component cell subsystems identified as critical for system function. EAGER proposals encouraged for submission in response to this DCL must include the prefix “RoL: EAGER: DESYN-C3” in front of the title. Please note that the maximum for EAGER awards is $300,000 for a maximum period of 2 years. Please see the PAPPG, Chapter II.E.2 for further information on EAGER proposal guidelines. Following encouragement to submit, full proposals must be submitted by July 12, 2018.
  • RAISE projects encouraged for submission should support innovative research into “pseudo-cell” functions by multidisciplinary teams. RAISE proposals encouraged for submission in response to this DCL must include the prefix “RoL: RAISE: DESYN-C3” in front of the title. Requests may be for up to $1,000,000 and up to five years in duration. The award size and duration will be consistent with the project scope. Please see PAPPG, Chapter II.E.3 for further information on RAISE proposal guidelines. Following encouragement to submit, full proposals must be submitted by July 12, 2018.


General and procedural inquiries should be directed to

Specific questions pertaining to this Dear Colleague Letter can be directed to the following cognizant Program Directors:

Dawn M. Tilbury
Assistant Director (ENG)

Anne L. Kinney
Assistant Director (MPS)

OPPORTUNITY – National Science Foundation (NSF) Dear Colleague Letter: ENG-EPSRC Lead Agency Activity

NSF 18-067

Dear Colleague Letter: Special Guidelines for Submitting Collaborative Proposals under the Division of Chemical, Bioengineering, Environmental, and Transport Systems, the Division of Civil, Mechanical and Manufacturing Innovation, and the Division of Electrical, Communications and Cyber Systems – the UK Engineering and Physical Sciences Research Council (ENG-EPSRC) Lead Agency Activity

April 13, 2018

Dear Colleagues:

The Directorate for Engineering (ENG), Division of Chemical, Bioengineering, Environmental and Transport Systems (CBET), the Division of Civil, Mechanical and Manufacturing Innovation (CMMI), and the Division of Electrical, Communications and Cyber Systems (ECCS) of the National Science Foundation and the Engineering, ICT and Manufacturing the Future Themes of the UK Engineering and Physical Sciences Research Council (EPSRC) are pleased to announce the ENG-EPSRC Lead Agency Activity. The goal of this activity is to reduce some of the barriers that researchers currently encounter when working internationally. The ENG-EPSRC Lead Agency Activity will allow US and UK researchers to submit a single collaborative proposal that will undergo a single review process.

Proposals will be accepted for collaborative research in areas at the intersection of CBET, CMMI, and/or ECCS with the EPSRC Engineering, ICT and/or Manufacturing the Future Themes’ programs. Proposers should review the CBET, CMMI, and ECCS Program Descriptions for research supported through these divisions and the EPSRC website for further information on what areas of research are eligible for support through this activity. Proposals are expected to adhere to typical proposal budgets and durations for the relevant CBET, CMMI, and ECCS programs and EPSRC Themes from which funding is sought.

A list of participating ENG programs in CBET, CMMI, and ECCS can be found at Please note that this activity ONLY includes unsolicited core programs in these divisions. No cross-cutting or agency-wide special programs are eligible.

Relevant EPSRC Programs can be found at

This document provides guidelines for the preparation, submission, review, and award of ENG-EPSRC Collaborative Proposals.


  1. Before submitting a proposal, researchers should identify a prospective lead agency (either NSF or EPSRC) based on where the largest proportion of their research lies.
  2. For proposers to be invited to submit a formal proposal, an expression of interest/white paper must be submitted no later than July 1, 2018, containing:
    1. An indication of the target program in both NSF-ENG and EPSRC for the proposed topic. Please note this is not the only program that will consider the topic, but it allows for faster review of the topic.
    2. A brief description of the proposed research – a breakdown of the UK/US components,
    3. The names and affiliations of the researchers, and
    4. Bottom line estimates of total funding (including indirect costs) to be requested from NSF and EPSRC (a detailed budget is not required at this time).
  3. If NSF is the lead agency, proposers should email the white paper to; the document should not exceed 5000 characters (including spaces).
  4. If EPSRC is the lead agency, the expression of interest must be submitted using the Smart Survey at
  5. If this communication has not taken place, the proposal will be returned without review.
  6. Please note that this due date of July 1, 2018, is a deadline requirement of all participating programs for this lead agency activity, including those with varying submission windows or open deadlines.
  7. The lead agency will share all expressions of interest/white papers received with the non-lead agency in order for both agencies to validate whether the proposed research is within the participating agencies’ portfolio, and if the institutions meet agency eligibility requirements).
  8. Upon confirmation from both agencies that the collaborative research proposal is appropriate for the ENG-EPSRC Lead Agency Activity, the agencies will decide which agency will act as lead. The lead agency will then contact the researchers to inform them that they may submit a full research proposal to the lead agency. In some cases, an alteration of the NSF and/or the EPSRC budget request may be required in the full proposal submission.

Special proposal preparation requirements include:

  1. The proposal should indicate it is to be considered under this Lead Agency Activity by prefacing the title with “CBET-EPSRC”, “CMMI-EPSRC”, or “ECCS-EPSRC” depending on the NSF division that will perform the proposal review.
  2. If NSF is the lead agency:
    1. Proposers must comply with the proposal preparation requirements outlined in NSF’s Proposal & Award Policies & Procedures Guide (PAPPG). The proposal must be submitted via either NSF’s FastLane system ( or ( to the appropriate standing program within CBET.
    2. The proposal should only include the funds requested from NSF on the Budget. A detailed breakdown of funding requested from EPSRC, using the EPSRC Je-S form, should be included as a Supplementary Document. This document will be shared with EPSRC to verify the eligibility of funds requested. The Budget Justification should address the full project budget (that is, both the US and UK funding items).
    3. The UK investigators should be included as “non-funded senior personnel’. A Biographical Sketch for each of these individuals should be provided in the Biographical Sketch section of the proposal with a format that conforms to the NSF PAPPG guidelines. Current and Pending Support” information for UK investigators does not have to be provided, however, the form can be left blank, entered as “0”, or “none”. A “Results of Prior Support” Section also is NOT required for the UK personnel.
  3. If EPSRC is the lead agency:
    1. Proposers must comply with the proposal preparation requirements outlined in the EPSRC’s Research Funding Guide and proposals should be submitted via the Je-S system ( through EPSRC standard mode via the ‘NSF(ENG)-EPSRC: EPSRC-Led Peer Review’ call.
    2. The proposal should only include the UK funds requested on the Je-S form. The US collaborating research organizations should be included as project partners on the Je-S form, and the funding totals by research organization should be included as project partner contributions. The Justification of Resources attachment should include a clear summary and justification of the funds requested from NSF, as well as the fund requested from EPSRC. In addition, a detailed breakdown of funding requested from NSF should be submitted to EPSRC as an Other Attachment. The latter document will be shared with NSF to verify the eligibility of funds requested.
  4. Proposals that request duplicative funding from NSF and EPSRC may be returned without review.
  5. An institutional statement in support of the joint submission must be provided by each non-lead country partner organization in the proposal submission. This statement should be in the form of a signed letter from an authorized institutional representative including the following text: “I confirm on behalf of [insert name or institution] that the US-UK Collaborative proposal between [insert name of lead agency PI and institution] and [insert non-lead agency PI and institution] is endorsed and has been submitted by [name of research office].” For NSF this letter must be included in the Supplementary Documents; for EPSRC the letter should be provided as a cover letter to the proposal.


ENG-EPSRC collaborative proposals will be reviewed alongside all other unsolicited proposals received in the same funding round and will not undergo a separate or special review process.

Proposals will be reviewed in accordance with the lead agency’s review criteria. While not identical, NSF and EPSRC ask reviewers to evaluate research on both its scientific or intellectual merit as well as its broader or societal impacts.


The lead agency and the non-lead agency will use their standard internal procedures to make their funding decision. The non-lead agency’s funding decision will be informed by the lead agency’s panel recommendation and funding decision.

NSF and EPSRC will confirm a final recommendation for funding with each other. Each agency reserves the right to fund their own country’s researchers, regardless of the other lead agency’s decision to fund or not. NSF and EPSRC reserve the right to negotiate final budgets with PIs prior to award.

All proposers will be advised whether their proposal has been recommended for funding or will be declined by the lead funding agency. Proposers will receive copies of the unattributed reviewers’ comments and, where applicable, a panel summary.

Once a proposer has been notified of a pending award, the non-lead researcher(s) associated with the project must submit a copy of the proposal to the non-lead agency so that each agency has complete documentation of the overall proposed research project. Where EPSRC is the non-lead agency a Je-S form and mandatory attachments must be submitted through EPSRC standard mode at this stage.

Because the participating organizations have different funding cycles, it is possible that some projects will have delayed start dates in order to wait until funds become available.

Should a proposal be declined for funding, proposers should refer to each agency’s individual resubmission policies.


Awardees must comply with the award conditions and reporting requirements of the agencies from which they receive funding.

Awardees will be required to acknowledge both NSF and EPSRC in any reports or publications arising from the grant.

Requests for changes to awards will be discussed with other involved funding agencies before a mutual decision is reached.

All NSF and EPSRC requirements for data management are applicable to investigators funded by their respective agencies.

In accordance with NSF and EPSRC standard procedures, awards are announced publicly.

For projects involving human subjects/participants or vertebrate animals, proposers should consult both EPSRC and NSF policies.

Dawn Tilbury
Assistant Director
Directorate for Engineering