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[Closes 17 May 2018] Dear Colleague Letter: Rules of Life (RoL): Design and Engineering of Synthetic Cells and Cell Components (DESYN-C3)

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.

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BACKGROUND

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.

RESEARCH CONCEPT OUTLINE SUBMISSION

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 SynCellDCL@nsf.gov 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.

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The Synthetic Biology Strategic Research Initiative provides a hub for anyone interested in Synthetic Biology at the University of Cambridge, including researchers, commercial partners and external collaborators.