Department Of E (Doe) Office Of S Biological And Environmental Esearch

environmental stewardship. As part of its mission, BER invests in crosscutting technologies andprograms to enable multiscale, systems-level research to achieve a predictive understanding ofsystems biology, biological community function, and environmental behavior. BSSD withinBER aims to provide the necessary fundamental science to understand, predict, manipulate, anddesign biological processes that underpin innovations for bioenergy and bioproduct research andto enhance our understanding of natural environmental processes relevant to DOE. BSSDsupports fundamental research to understand the systems biology of plants and microbes throughthe GSP. The GSP’s portfolio includes systems biology research that builds on a foundation ofmulti-omics data and integrates multidisciplinary experimental and computational approaches.Within this framework, one of the objectives of the GSP is to develop the next generation ofgenome engineering technologies to unlock the potential of plants and microorganisms for thesafe and efficient conversion of renewable biomass, captured CO2 from the atmosphere, and/orpetroleum-derived polymers into fuels, valuable chemicals, and materials with novel properties,advancing towards a sustainable and secure bioeconomy. The iterative application and testing ofthose engineering technologies to design living organisms with new functional properties alsoleads to a deeper understanding of the fundamental principles governing those organisms.Therefore, this “design, build, test, learn” (DBTL) cycle not only results in improved biosystemsdesign, but also leads to a more comprehensive knowledge of relevant biological systems.During the last decade, the fields of systems and synthetic biology and artificial intelligence haveseen momentous advances that have dramatically accelerated the DBTL cycle for engineeringbiology. More efficient approaches for genome-wide editing, analysis, and phenotyping becomeavailable, and new computational tools and modeling algorithms can handle increasingly largedatasets while continuously improving their prediction accuracy. To bring these advances to thenext level, integrative multidisciplinary applications are solicited for highly innovative,fundamental multi-omics and systems biology research and technology development forbiosystems design. Applications should respond to one of the following two research topics:a) Microbial biosystems design for the production of biofuels, bioproducts, andbiomaterialsApplications should pursue multidisciplinary approaches to develop genome-wide designand editing, and in vivo or cell-free engineering technologies for eukaryotic orprokaryotic microbes to produce biofuels, bioproducts, or biomaterials fromlignocellulosic biomass, petroleum-derived synthetic polymers, or as a byproduct ofphotosynthesis. Applications are expected to propose the development of highlyinnovative, high-throughput platforms for biological design and testing, supported byadvanced modeling and computational tools. A focus on new or emerging model systemsto expand the breadth of platform microorganism for engineering is encouraged. Genomeengineering strategies to develop organisms that efficiently produce chemicals ormaterials while sequestering atmospheric CO2 are also encouraged. Research areas ofinterest include but are not limited to: i) in vivo, cell-free, or intercellular systems toconfer new functionalities such as biosensors, tunable genetic circuits, and subcellularcompartmentalization that enable the synthesis of desirable products; ii) orthogonalmetabolic, macromolecular synthesis, and signaling pathways that equip cells tobiologically carry out processes not found in nature; iii) design of recoded, minimal,and/or synthetic genomes with novel properties; iv) engineering microorganisms that can2

break down petroleum-derived synthetic polymers and/or convert them into valuableproducts; and v) design and engineering microorganisms for the production ofbiominerals, inorganic-organic composites, and composites of inorganic materials andliving cells (living materials) with wholly new properties not found in known organisms.b) Plant biosystems design for bioenergy, bioproducts, and biomaterialsApplications should focus on integrative studies to engineer plant systems to achievesustainable production of biofuels, bioproducts, and biomaterials; substantially improvebioenergy crop performance in marginal environments; and/or increase biomass yieldwhile making it more amenable to deconstruction and conversion into desirablechemicals. Relevant goals for crop design and engineering include but are not limited to:i) increasing abiotic stress tolerance, ii) achieving higher water and/or nutrient useefficiency, iii) improving photosynthetic capacity, iv) facilitating cell wall deconstructionand subsequent conversion to advanced biofuels and bioproducts, and v) engineering theproduction of bioproducts or biomaterials. Proposed research should include innovativetechnologies for the introduction and expression of large, stable, multigene DNAconstructs, genome-wide editing and recombineering, and high-throughput phenotyping,supported by computational approaches for modeling and design. Epigenetic engineeringapproaches to attain programable and tunable gene expression across the genome areencouraged. Research on model plants should be kept to a minimum and the main focusof the applications should be on potential or emerging bioenergy crops, including but notlimited to switchgrass, poplar, Miscanthus, eucalyptus, sorghum, energy cane, and nonfood oilseed crops.Applications must include strategies to address biocontainment, minimizing risks ofpotential release of engineered organisms into the environment or other unintendedoutcomes.BER encourages the submission of innovative “high-risk/high-reward” research applications thataddress critical knowledge gaps and have the potential for high impact. The probability ofsuccess and the risk-reward balance will be considered when making funding decisions.Applications that propose incremental advances in existing technologies or knowledge are notencouraged.The following areas are NOT within the scope of this FOA: Starch-, waste-, natural gas- orcoal-derived biofuels, bioproducts or biomaterials; microbial fuel cells; electrosynthesis;wastewater; municipal solid waste; bioremediation; bioprospecting; biomimetics/biohybrids;food crops; production of ethanol, biogas, hydrogen, pharmaceuticals, nutraceuticals, cosmetics,or food products. Projects focused on titer/yield improvement or scale-up production inestablished microbial systems are not within the scope of BSSD. Research that would result inonly incremental knowledge or technological advances, or applications focused solely ontechnology development will not be considered.References:Further information on BER’s vision for biosystems design research as well as relevant reportsand previously funded projects can be found in the BER Biosystems Design webpage3

). Information on previous GSP awards anda description of the Program’s goals and overall organization can be found athttp://genomicscience.energy.gov.DOE User Facilities and other specialized resources: Applicants are encouraged to considerthe use of resources provided by DOE Science User Facilities and Community Resources. Theseinclude the DOE Systems Biology Knowledgebase (KBase; http://www.kbase.us), the NationalMicrobiome Data Collaborative (NMDC; https://microbiomedata.org/), the DOE EnvironmentalMolecular Sciences Laboratory (EMSL; https://www.emsl.pnnl.gov/emslweb/), the NationalEnergy Research Scientific Computing Center (NERSC; http://www.nersc.gov), the DOE BERStructural Biology and Imaging Resources (https://berstructuralbioportal.org), and the DOE JointGenome Institute (JGI; http://jgi.doe.gov). Awarded projects will receive prioritizedconsideration for use of JGI capabilities through the Biological and EnvironmentalResearch Support Science (BERSS) user program . To determine the feasibility of the planned work to be done byJGI, applicants should contact JGI before submitting their application.Annual Principal Investigator (PI) meeting: If an award is made, beginning in the first year offunding, one or more project participants will be required to attend an annual PrincipalInvestigator (PI) meeting, generally held in the Washington, D.C., area. Reasonable travelexpenses may be included as part of the project budget.Open ScienceSC is dedicated to promoting the values of openness in Federally supported scientific research,including, but not limited to, ensuring that research may be reproduced and that the results ofFederally supported research are made available to other researchers. These objectives may bemet through any number of mechanisms including, but not limited to, data access plans, datasharing agreements, the use of archives and repositories, and the use of various licensingschemes.The use of the phrase “open-source” does not refer to any particular licensing arrangement, but isto be understood as encompassing any arrangement that furthers the objective of openness.Multi-Institutional TeamsSC uses two different mechanisms to support teams of multiple institutions: ‘CollaborativeApplications’ and ‘Subawards’.COLLABORATIVE APPLICATIONSCollaborative applications (in which each team member submits its own application with acommon research narrative) will not be accepted under this FOA.4

SUBAWARDS 1Multi-institutional teams must submit one application from a designated lead institution with allother team members proposed as subrecipients.DOE/National Nuclear Security Administration (NNSA) National Laboratories 2, other Federalagencies, and another Federal agency’s FFRDCs 3, if participating in a team led by anotherinstitution, must be proposed as subrecipients.Note that the value of any such proposed subaward will be removed from any such prime award:DOE will make separate awards to Federally affiliated institutions.1 Subawards are made to subrecipients. Both terms are defined in 2 CFR 200.1 (https://www.ecfr.gov)2 The phrase “National Laboratories” is used broadly to encompass DOE/NNSA laboratories and sites capable ofperforming the work described in this FOA and capable of receiving funds through the DOE Field Work System.3 An authoritative list of all Federally Funded Research and Development Centers (FFRDCs) may be found athttps://www.nsf.gov/statistics/ffrdclist/5

Section II – AWARD INFORMATIONA. TYPE OF AWARD INSTRUMENTDOE anticipates awarding grants under this FOA.Multi-institutional teams must apply using a prime and subaward model with one applicationsubmitted by the lead institution.B. ESTIMATED FUNDINGDOE anticipates that, subject to the availability of future year appropriations, a total of 110million in current and future fiscal year funds will be used to support awards under this FOA.DOE is under no obligation to pay for any costs associated with preparation or submission ofapplications. DOE reserves the right to fund, in whole or in part, any, all, or none of theapplications submitted in response to this FOA.C. MAXIMUM AND MINIMUM AWARD SIZEThe award size will depend on the number of meritorious applications and the availability ofappropriated funds. The ceiling and floor described in this FOA represent the expected range ofaward sizes. Applicants should request sufficient funding to achieve their proposed results.Ceiling 5,000,000 per year. Applications requesting more than this amount of support may be declinedwithout further review.Floor 1,000,000 per year.D. EXPECTED NUMBER OF AWARDSApproximately six to 12 awards are expected.The exact number of awards will depend on the number of meritorious applications and theavailability of appropriated funds.E. ANTICIPATED AWARD SIZEIt is anticipated that award sizes may range from 1,000,000 per year to 5,000,000 per year.The award size will depend on the number of meritorious applications and the availability ofappropriated funds.6

F. PERIOD OF PERFORMANCEDOE anticipates making awards with a project period of five years.Continuation funding (funding for the second and subsequent budget periods) is contingent on:(1) availability of funds appropriated by Congress and future year budget authority; (2) progresstowards meeting the objectives of the approved application; (3) submission of required reports;and (4) compliance with the terms and conditions of the award.G. TYPE OF APPLICATIONDOE will accept only new applications under this FOA. Applications for the renewal of or for asupplement to an existing award will not be accepted. Applications that propose work that willbuild on an existing or prior award must be submitted as new applications.7

Section III – ELIGIBILITY INFORMATIONA. ELIGIBLE APPLICANTSAll types of applicants are eligible to apply, except nonprofit organizations described in section501(c)(4) of the Internal Revenue Code of 1986 that engaged in lobbying activities afterDecember 31, 1995.Federally affiliated 4 entities must adhere to the eligibility standards below:1. DOE/NNSA National LaboratoriesDOE/NNSA National Laboratories are not eligible to submit applications under this FOA butmay be proposed as subrecipients under another organization’s application. If recommended forfunding as a proposed subrecipient, the value of the proposed subaward will be removed fromthe prime applicant’s award and will be provided to the laboratory through the DOE Field-WorkProposal System and work will be conducted under the laboratory’s contract with DOE. Noadministrative provisions of this FOA will apply to the laboratory or any laboratorysubcontractor. Additional instructions for securing authorization from the cognizant ContractingOfficer are found in Section VIII of this FOA.2. Non-DOE/NNSA FFRDCsNon-DOE/NNSA FFRDCs are not eligible to submit applications under this FOA but may beproposed as subrecipients under another organization’s application. If recommended for fundingas a proposed subrecipient, the value of the proposed subaward may be removed from the primeapplicant’s award and may be provided through an interagency agreement to the FFRDC’ssponsoring Federal Agency. Additional instructions for securing authorization from thecognizant Contracting Officer are found in Section VIII of this FOA.3. Other Federal AgenciesOther Federal Agencies are not eligible to submit applications under this FOA but may beproposed as subrecipients under another organization’s application. If recommended for fundingas a proposed subrecipient, the value of the proposed subaward may be removed from the primeapplicant’s award and may be provided through an interagency agreement. Additionalinstructions for providing statutory authorization are found in Section VIII of this FOA.This FOA seeks to support basic research to advance understanding rather than to addresscommercial opportunities. Applications that propose research related to current commercialactivity or current customer needs may be declined without merit review.4 Institutions that are not DOE/NNSA National Laboratories, a non-DOE/NNSA FFRDC, or another Federal agencyare not Federally affiliated, even if they receive Federal funds or perform work under a Federal award or contract.8

Applications that are submitted by applicants that have not submitted a required pre-applicationmay be declined without further review.B. COST SHARINGCost sharing for basic and fundamental research is not required pursuant to an exclusion from therequirements of Section 988 of the Energy Policy Act of 2005.C. ELIGIBLE INDIVIDUALSIndividuals with the skills, knowledge, and resources necessary to carry out the proposedresearch as a Principal Investigator (PI) are invited to work with their organizations to developan application. Individuals f

department of energy (doe) . office of science (sc) . b. iological and . e. nvironmental . r. esearch (ber) b. iosystems design to enable safe production of next-generation biofuels, bioproducts, and biomaterials. funding opportunity announcement (foa) number: . de-foa-0002600 . foa type: amendment 000001 . cfda number: 81.049. foa issue date: december 9, 2021 submission deadline for pre .