Department Of Energy (Doe) Office Of Science Biological And .

Advances in ‘omics technologies together with computational modeling and data analysis areenabling the gathering of information on critical and complex plant processes such asmetabolism, development, and signaling. Although immense amounts of data can be generatedby these methodologies, much of the functional information obtained from them is generated bycorrelation analysis and computational inference, lacking causal and verifiable knowledge.Experimental characterization of gene function continues to be a significant bottleneck,hampering our ability to fully exploit the potential of available ‘omics data. This in turn limitsdirect understanding of how genes regulate organismal function and ultimately the ability toaccurately assign and validate gene function in non-model organisms. By elucidating complexregulatory processes at the molecular, cellular, and organismal levels, a better understanding ofplants as a whole and a more accurate prediction of plant behavior under varying conditions canbe achieved.To overcome these obstacles, more efficient, high-throughput methods for interpretingexperimental evidence need to be developed for accurate determination of gene function. Whileexperimental approaches are unlikely to scale with advances in ‘omics technologies,concentrated development and application of new approaches are required to tackle this criticalknowledge gap of genomics space. The overarching goal of this FOA is to address the challengesand opportunities in associating gene(s) to function (i.e., genotype to phenotype) in plant systemsof relevance to the BER mission in energy and the environment.Specifically, this FOA seeks applications that employ systems biology and high throughputapproaches to elucidate and validate the functional roles of genes, gene families, and associatedpathways related to physiological and metabolic processes such as CO2 sequestration and belowground storage; nutrient and water use efficiency; tolerance and/or resistance to abiotic stressessuch as drought and temperature extremes; developmental processes critical to enhanced biomassyield and optimization or extension of growth range; and metabolism of oils and fatty acids forbiofuels and bioproducts.Projects of interest should include one or more of the following:a) Comprehensive investigations of regulatory elements and mechanisms (e.g., transcriptionfactors, cis-regulatory regions, enhancers, insulators, epigenetic regulation, alternativesplicing mechanisms, etc.) to validate regulation of gene expression;b) Approaches to functionally understand gene families to elucidate regulatory differencesamong members, sub-functionalization, and functional divergence, particularly in largegene families; and/orc) Dissection of multigene traits (e.g., yield) into its genetic components andcharacterization and validation of molecular genetic functions for these components, withan aim towards understanding their impacts on the final phenotype.The proposed research should focus on expeditiously gathering the experimental evidenceneeded to understand gene function in plants; to accelerate experimental plant gene functiondiscovery and validation; and to implement new and innovative ways to combine experimentaland computational methods to study gene function. Projects should involve comprehensive,integrative, systems biology approaches that may include biochemical and physiologicalmethods coupled with computation, engineering, robotics, and other disciplines and technologies2

to develop higher-throughput systems for gene function determination. While development ofnew approaches is expected and encouraged, applications focused solely on tool and/or methoddevelopment will not be considered responsive.Examples of species of interest include candidate bioenergy plants (e.g., sorghum, switchgrass,Populus) and oilseed crops (e.g., Camelina). Additionally, duckweed (Lemnaceae) as a source ofbiofuel/bioproducts will be considered. Research using model species such as Arabidopsis,Brachypodium, Chlamydomonas, and Nicotiana is acceptable if the applicant demonstrates clearrelevance of the focal genetic system to the DOE BER mission in bioenergy and bioproducts aswell as potential for translation to bioenergy crops.This FOA continues a program area initiated in Fiscal Year (FY) 2019 and supported by the2018 DOE BER workshop “Breaking the Bottleneck of Genomes: Understanding Gene FunctionAcross Taxa” dex.shtml).NOTE: BER encourages the submission of innovative "high-risk/high-reward" researchapplications that address critical knowledge gaps and have the potential for high impact. Theprobability of success and the risk-reward balance will be considered when making fundingdecisions. This FOA encourages individual investigators as well as interdisciplinary teams thatassemble a range of expertise into a coordinated approach. For the latter situation, applicantsmust include a clear plan describing the individual contributions of each participant, as well as anoverall management plan.The following areas are not within the scope of this FOA: Research that seeks to increasestarch content for improved nutrient qualities; to facilitate the digestion and fermentation ofstarch to produce sugars and other bio-based products or biofuels; to improve soybean, foodgrade canola or other oilseed crops to be used as a food source or for pharmaceutical or cosmeticuse; or to increase grain yields or food yields for human consumption. Proposals targeting nonterrestrial plants, with the exception of Lemnaceae and Chlamydomonas as described above, willnot be considered under this FOA.Information about the DOE Genomic Science Program data release policy, with which awardeeswill be expected to comply, is available ex.shtml. Any application submitted withouta data sharing and digital data management plan, including gene function data, will bedeclined without review.Annual Principal Investigator (PI) Meeting: If a project is funded, beginning in the first yearof funding, one or more project participants will be required to attend an annual GenomicScience Program Principal Investigator (PI) meeting, generally held in the Washington, D.C.,area. Reasonable travel expenses may be included as part of the project budget.Applicants are encouraged to visit the GSP website for more detailed information about theprogram: http://www.genomicscience.energy.gov/.Availability of User Facilities and Other Specialized Resources: DOE has responsibility for3

programs and facilities that offer unique and complementary resources that support research in awide variety of science areas. Applicants are encouraged to consider utilization or collaborationwith DOE-funded facilities that have existing and dedicated financial support, thereby leveragingongoing infrastructure investments, archived samples, User Facilities, and long-term data setswhen developing their applications.For Joint Genome Institute (JGI) and Environmental Molecular Sciences Laboratory (EMSL)capabilities (see table below), applicants should assess whether the project’s needs are withinreasonable requests for the respective User Facility and reach out to the respective user programcoordinator if the request might be considered large. Awarded projects will receive prioritizedconsideration for use of JGI capabilities through the Biological and Environmental SupportScience (BERSS) program ), subject to anassessment of technical feasibility by the facility.Examples of available user facilities and other specialized resources MSL)The Environmental Molecular Sciences Laboratory (EMSL)(http://www.emsl.pnl.gov/) located at the Pacific Northwest NationalLaboratory, is a DOE Office of Science User s/). EMSL empowers scientificdiscovery of the mechanisms and dynamics that drive biological andenvironmental processes and interactions by providing users access topremier instruments for experimental research as well as highperformance computing (HPC) and a variety of software codes for arange of modeling and simulation studies. Experimental capabilitiesavailable include: advanced chemical imaging/microscopy of dynamicinter- and intracellular processes; nanoSIMS; computed x-raytomography; high-resolution mass spectrometry and NMR spectroscopyfor transcriptomics, metabolomics, and proteomics; plant/soil/subsurfacegrowth chambers; and software and associated hardware for moleculardynamics, metabolic process and multi-scale modeling/simulation aswell as data analytics. These and other experimental and computationalcapabilities are available at no charge through a user proposal opportunities). Applicantsare also encouraged to explore the Facilities Integrating Collaborationsfor User Science (FICUS) initiative between JGI and ntegrating-collaborationsuser-science-ficus), through which capabilities at both user facilities canbe combined and accessed with one proposal.4

HighPerformanceComputingCentersThe DOE Office of Science supports leadership and high performancecomputing User Facilities, which provide compute cycles and datastorage through a proposal process to the scientific community. Theseresources include the Molecular Science Computing (MSC) capability atEMSL mputing), theNational Energy Research Scientific Computing Center (NERSC) at theLawrence Berkeley National Laboratory (http://www.nersc.gov), theArgonne Leadership Computing Facility at Argonne National Laboratory(https://www.alcf.anl.gov/) and the Oak Ridge Leadership ComputingFacility at Oak Ridge National Laboratory (https://www.olcf.ornl.gov/).Joint GenomeInstituteThe Joint Genome Institute (JGI) in Berkeley, California, is a DOEOffice of Science User Facility that provides the scientific communityaccess to state-of-the-art genomic sequencing and analysis capabilities,as well as modest amounts of DNA synthesis and metabolomicscapabilities, for microbial, plant, microbial community, and other (nonpathogen) targets. In all cases, the aim of the JGI is to provide to thenational and international scientific community information on thegenome-derived “parts lists” that support further discovery(http://www.jgi.doe.gov). These resources are available at no chargethrough a user proposal process (see Approved User Proposals - DOEJoint Genome Institute). Applicants are also encouraged to explore theFacilities Integrating Collaborations for User Science (FICUS) initiativebetween JGI and EMSL, through which capabilities at these (andpotentially other) User Facilities can be combined and accessed with oneproposal tionalMicrobiomeDataCollaborative(NMDC)The National Microbiome Data Collaborative (NMDC;https://microbiomedata.org/) is an integrated microbiome data ecosystemhosting high-quality, consistently processed multi-omics microbiomedata to enable data sharing, management and cross-comparison studies inaccordance with the FAIR (Findable, Accessible, Interoperable,Reusable) data principles. Community-driven standards developed by theOpen Biological and Biomedical Ontology (OBO) Foundry (e.g., theEnvironment Ontology (EnvO)) and the Genomic Standards Consortium(GSC) (e.g., the Minimum Information about any (x) Sequence (MIxS))are applied to all project metadata and support the NMDC metadataschema (https://microbiomedata.org/metada). The NMDC hosts a varietyof interoperable and reusable annotated microbiome data productsprocessed through open-source analytic workflows .readthedocs.io) includingmetagenome, metatranscriptome, metaproteome, and metabolome data.The DOE User Facilities, the Joint Genome Institute (JGI) and5

Environmental Molecular Sciences Laboratory (EMSL), servecomplementary microbiome infrastructure (e.g., IMG/M and GOLD) andare integrated with the NMDC, while KBase can provide advancedbioinformatics capabilities leveraging NMDC data. For the pilot phase,the NMDC is developing infrastructure for all stages of the digital datalifecycle including capture, analysis, sharing, and preservation to supportdata management. Applicants are strongly encouraged to work withNMDC staff to ensure their data aligns with the NMDC metadata schemaand for the generation of multi-omic data products for inclusion in theNMDC.DOE SystemsBiologyKnowledgebase(KBase)The U.S Department of Energy Systems Biology Knowledgebase(KBase) (www.kbase.us) is an open-source software and data platformdesigned to meet the grand challenge of systems biology—predicting anddesigning biological function from the biomolecular (small scale) to theecological (large scale). KBase is available for anyone to use, andenables researchers to collaboratively generate, test, compare, and sharehypotheses about biological functions; perform large-scale analyses onscalable computing infrastructure; and combine experimental evidenceand conclusions that lead to accurate models of plant and microbialphysiology and community dynamics. The KBase platform has (1)extensible analytical capabilities (2) a web-browser-based user interfacethat supports building, sharing, and publishing reproducible and wellannotated analyses with integrated data; (3) access to extensivecomputational resources; and (4) a software development kit allowing thecommunity to add functionality to the system. Science done withinKBase is featured in peer-reviewed publications(http://kbase.us/publications) and the KBase Narratives associated withthese experiments are available to be copied, re-run and extended by all.Neutron BeamFacilitiesDOE provides the scientific community access to high flux neutronsources that are capable of providing structural and chemical informationoften unavailable using other technologies. DOE has two such facilitiesat the Oak Ridge National Laboratory, the Spallation Neutron Source(SNS; http://neutrons.ornl.gov/sns/) and the High Flux Isotope Reactor(HFIR; https://neutrons.ornl.gov/hfir/). Use of the neutron sources isavailable at no charge through a user proposal process. For moreinformation about the BER-supported structural biology resources at thesynchrotron and neutron facilities, visit:http://www.BERStructuralBioPortal.org.6

SynchrotronLight SourcesDOE provides the scientific community access to synchrotron lightsources that are capable of providing structural and chemical informationoften unavailable with conventional sources of x-rays. Use of eachsynchrotron light source is available at no charge through its userproposal process. Information about each DOE synchrotron User Facilitycan be found at: Argonne National Laboratory (http://www.aps.anl.gov/);Brookhaven National Laboratory (http://www.bnl.gov/ps/); LawrenceBerkeley National Laboratory (http://www.als.lbl.gov/); and StanfordSynchrotron Radiation Laboratory (http://wwwssrl.slac.stanford.edu/index.html). For more information about the BERsupported structural biology resources at the synchrotron and neutronfacilities, visit: http://www.BERStructuralBioPortal.org.Related ProgramsThe following programmatic areas within BER are at the interface with GSP’s plant genomicsportfolio:Systems Biology for Sustainable Bioenergy: The DOE-BER BSSD GSP portfolio insustainable bioenergy is focused on omics-driven basic research aimed at enabling theintegrated development of sustainable bioenergy feedstock systems in terrestrialenvironments within the ecosystem context. The development of integrative, physiologybased models to attain a systems-level understanding of the plant-soil-microbiomeecosystem and identify key parameters of bioenergy plant sustainability is encouraged.The emphasis is on key variables such as genomic properties of biofuel crops andrelevant biological processes (e.g., rhizosphere community functions, soil carbonstabilization, nutrient cycling, and greenhouse gas production) that enable quantitative,accurate prediction of plant performance and ecos

DEPARTMENT OF ENERGY (DOE) . OFFICE OF SCIENCE (SC) . BIOLOGICAL AND ENVIRONMENTAL RESEARCH (BER). GENOMICS-ENABLED PLANT BIOLOGY FOR DETERMINATION OF GENE FUNCTION. FUNDING OPPORTUNITY ANNOUNCEMENT (FOA) NUMBER: . DE-FOA-0002601 . FOA TYPE: INITIAL. CFDA NUMBER: 81.049. FOA Issue Date: December 16, 2021 Submission Deadline for Pre-Applications: January 14, 2022 at 5:00 PM Eastern Time