Quantitative Systems Biotechnology (QSB)
National Science Foundation
Full Proposal Deadline(s) (due by 5 p.m proposer's local time):
Quantitative Systems Biotechnology (QSB)
Synopsis of Program:
As a result of recent advances in genomic and biochemical analysis, informatics, mathematics, and the engineering disciplines, it is now possible to approach an understanding of the integrated processes which translate the information contained in the genome into functioning biological entities. Systems engineering approaches will be essential for characterizing the emergence of biological phenotypes from underlying hierarchies of interactions and environmental influences. Understanding the quantitative systems behavior of cellular systems is important in its own right as well as providing a conceptual basis for biotechnological process development.
This Quantitative Systems Biotechnology solicitation seeks innovative high-risk/high-return proposals, which combine in-depth analysis of large-scale cellular biological systems, or their representations, with creative software tools for the development of computer models as well as complementary quantitative experimental approaches. Multidisciplinary proposals are encouraged.
Cognizant Program Officer(s):
Applicable Catalog of Federal Domestic Assistance (CFDA) Number(s):
Impressive gains in genome sequencing technology and the growing number of completely or nearly sequenced naturally occurring or engineered genomes have generated substantial data. The heightened availability of this genome-level data provides new opportunities for systems-based analyses and modeling of cellular systems and biotechnological processes. At the same time, advances in high performance computing, massive data storage, and new computational paradigms provide opportunities to approach this challenge quantitatively and computationally. In addressing the relationship between genotype and phenotype, and to accelerate progress towards realizing associated biotechnological opportunities, this program supports high risk/high return research devoted to developing, adapting, and exploiting systems analysis frameworks and data acquisition systems that hold promise for more efficiently relating genome- and environment-level data to a manifested phenotype.
The phenotype results from the interactions among numerous gene products and environmental factors, and so is best understood from a systems viewpoint. The construction and testing of quantitative frameworks, in turn, will be enabled by the collaborative input of bioengineers, complex systems analysts, biologists, and workers from other fields to contend creatively with the hierarchical and nonlinear nature of cellular systems, while maintaining a focus on directing the research results towards developing and improving cell-based, biotechnological processes. These frameworks may involve the use of different system analysis tools (discrete math, differential equations, complex systems simulation) and model-database integration architectures. Moreover, the engineering design and performance space for quantitative investigation may extend far beyond the examples and circumstances provided by nature and, consequently, may involve unusual analysis frameworks and phenotype drivers.
Highly defined biological systems will be required for developing such quantitative frameworks. At this juncture, unicellular or engineered unicellular organisms are perhaps the most desirable subjects for developing quantitative frameworks, as more rapid progress is possible when substantial genomic data are combined with the ability to more completely define phenotype as well as identify environmental conditions under which proliferation and gene expression occur.
Opportunities and needs also exist regarding data acquisition systems (e.g. arrays, two-dimensional gels). It would be beneficial, for example, to move beyond the output of data in ratio form so that the information can be more immediately used for model building or testing. New approaches that yield information that can, for example, link gene array, proteomic, and metabolic data sets in the context of understanding metabolic and signal transduction pathways are also important research objectives.
Additional information on QSB is available at the following web site, which reports on a QSB Workshop held at the National Science Foundation (NSF) on September 13-14, 2000:
Two grant competitions for QSB have already been held (NSF 01-37 and NSF 02-026). The first competition resulted in 11 Awards (5 exploratory and 6 standard Awards) with a total funding level of $3.1M while the second competition resulted in 7 Awards (2 exploratory and 5 standard Awards) with a total funding of $2.5M. This is the third competition of an anticipated multiyear activity for QSB.
OVERALL GOALS & SCOPE
The ultimate goals of the QSB initiative are to:
These goals must be approached using non-reductionist modeling approaches and improved data acquisition and integration methods.
In a typical case, it is likely that work supported by this initiative will use as components a set of known gene products, or sequences, whether coding or non-coding, a set of regulators, and/or a number of metabolites and pathways, and connect them in a fashion that would elucidate aspects of their integrated function, coordination, regulation, and role in phenotype determination. The detailed analysis of molecular mechanisms (e.g. ligand binding, protein-protein interactions, and molecular recognition) falls within the scope of QSB if the task is imbedded in an integrated assessment that shows promise for enhancing understanding at the intact system level.
There is no doubt that the identification and characterization of individual genomic or metabolic components is of extreme importance. However, the scope of QSB emphasizes the quantitative interactions between such components and the consequent phenotype. Thus, research focused on molecular component characterization falls outside the scope of QSB. The scope of the QSB initiative also does not embrace a focus on sequencing, genomic data acquisition, or statistical mining. Proposals may include such methodologies only in conjunction with other substantive system modeling tasks. Proposals on new screening strategies and assay technologies are encouraged if they demonstrate novelty and also explicitly address how quantitative modeling efforts will be enabled and pursued.
A responsive proposal should describe an overarching issue and present a solution path involving system analysis and/or experimentation. Some of the general topics of interest include:
As described above, analysis and experimentation should be viewed as linked even if a proposed project emphasizes modeling versus experimentation. The following questions provide examples of some issues of interest. The examples are not meant to be inclusive; other integrative questions and the technological implications of the answers also merit investigation.
Quantitative Frameworks: Modeling work can be anticipatory or hypothesis-driven in that one need not delay the development of models until all necessary data are acquired. The fusion of different computational tools is highly encouraged as a means of addressing physicochemical and informational hierarchies, molecular biology, and other salient system features. Such frameworks may combine differential equations, discrete mathematics, and other system analysis tools. Other formalism issues such as revisiting how models connect with data bases to enable the prediction of emergent, branching, and other properties are of interest.
All models should be appropriately tested with respect to robustness and sensitivities to changes in parameters. The models should produce testable results and also guide the development of new experiments. It is desirable that the proposed program include model testing and validation in collaboration with bench scientists.
Screening & Data Acquisition Systems: Methods and strategies offering increased reliability, reproducibility, and resolution for gene expression and protein profiling are required. Such data must have the attribute of being more directly useable for quantitative model development and/or testing. In particular, moving beyond ratio analysis is needed where, for example, the information provided is in the form of molecules per cell, concentration, etc. This may involve inventing new methods or improving the output from existing methods. Apart from screening systems, new biomolecular screening strategies also need to be developed that allow for the link between gene expression (e.g. gene chip) and proteomic data to be more firmly established. Examples include new assay strategies for ascertaining metabolite profiles and second messenger levels.
Subject Systems: Unicellular or engineered unicellular organisms are viewed as the most desirable research subjects for progress to be made in the near term while also providing a platform for investigating other biological systems. The genome of the organism (or strain) need not be totally sequenced if the project entails using that organism for proving the concept behind a new screening or assay approach. However, the data-acquisition advances must have high potential for being applicable to organisms with completed genome sequences. Additionally, researchers must be cognizant of potential limitations when focusing on an organism to insure that valid conclusions are drawn and the results are not overly extrapolated. Biological modularity and common design-property relationships may exist, yet there may also be interesting variations when an organism's natural environmental niche versus a synthetic bioprocess (or laboratory) environment is considered. Therefore, some careful advance thinking and interpretative flexibility are desirable attributes of research programs, especially when delineating design rules and general patterns that comprise the goals.
Full Proposal Instructions:
Proposals submitted in response to this program announcement/solicitation should be prepared and submitted in accordance with the general guidelines contained in the NSF Grant Proposal Guide (GPG). The complete text of the GPG is available electronically on the NSF Website at: https://www.nsf.gov/cgi-bin/getpub?gpg. Paper copies of the GPG may be obtained from the NSF Publications Clearinghouse, telephone (301) 947-2722 or by e-mail from firstname.lastname@example.org.
Proposers are reminded to identify the program announcement/solicitation number (03-517) in the program announcement/solicitation block on the NSF Cover Sheet For Proposal to the National Science Foundation. Compliance with this requirement is critical to determining the relevant proposal processing guidelines. Failure to submit this information may delay processing.
No cost sharing is required for equipment costs under $20,000. Cost sharing is required for equipment costs over $20,000, as follows:
~ 50% cost sharing is required for equipment costs between $20,000 and $100,000 (i.e., if total equipment cost is $40,000, NSF will award $20,000 for equipment, and the grantee will cost share $20,000).
~ For equipment costs above $100,000, NSF will award a maximum of $50,000 for equipment, and the remainder will be cost shared by the grantee (i.e. if total equipment cost is $160,000, NSF will award $50,000 for equipment, and the grantee will cost share $110,000).
Use the GPG definition of equipment for cost sharing requirement purposes, and submit equipment cost breakdown with the budget justification.
The proposed cost sharing must be shown on Line M on the proposal budget. Documentation of the availability of cost sharing must be included in the proposal. Only items which would be allowable under the applicable cost principles, if charged to the project, may be included as the awardee's contribution to cost sharing. Contributions may be made from any non-Federal source, including non-Federal grants or contracts, and may be cash or in-kind (see OMB Circular A-110, Section 23). It should be noted that contributions counted as cost-sharing toward projects of another Federal agency may not be counted towards meeting the specific cost-sharing requirements of the NSF award. All cost-sharing amounts are subject to audit. Failure to provide the level of cost-sharing reflected in the approved award budget may result in termination of the NSF award, disallowance of award costs and/or refund of award funds to NSF.
Indirect Cost (F&A) Limitations:
Other Budgetary Limitations:
Proposals must be submitted by the following date(s):
Full Proposal Deadline(s) (due by 5 p.m proposer's local time):
Proposers are required to prepare and submit all proposals for this announcement/solicitation through the FastLane system. Detailed instructions for proposal preparation and submission via FastLane are available at: http://www.fastlane.nsf.gov/a1/newstan.htm. For FastLane user support, call the FastLane Help Desk at 1-800-673-6188 or e-mail email@example.com. The FastLane Help Desk answers general technical questions related to the use of the FastLane system. Specific questions related to this program announcement/solicitation should be referred to the NSF program staff contact(s) listed in Section VIII of this announcement/solicitation.
Submission of Electronically Signed Cover Sheets. The Authorized Organizational Representative (AOR) must electronically sign the proposal Cover Sheet to submit the required proposal certifications (see Chapter II, Section C of the Grant Proposal Guide for a listing of the certifications). The AOR must provide the required electronic certifications within five working days following the electronic submission of the proposal. Proposers are no longer required to provide a paper copy of the signed Proposal Cover Sheet to NSF. Further instructions regarding this process are available on the FastLane Website at: http://www.fastlane.nsf.gov
Reviews of proposals submitted to NSF are solicited from peers with expertise in the substantive area of the proposed research or education project. These reviewers are selected by Program Officers charged with the oversight of the review process. NSF invites the proposer to suggest, at the time of submission, the names of appropriate or inappropriate reviewers. Care is taken to ensure that reviewers have no conflicts with the proposer. Special efforts are made to recruit reviewers from non-academic institutions, minority-serving institutions, or adjacent disciplines to that principally addressed in the proposal.
The National Science Board approved revised criteria for evaluating proposals at its meeting on March 28, 1997 (NSB 97-72). All NSF proposals are evaluated through use of the two merit review criteria. In some instances, however, NSF will employ additional criteria as required to highlight the specific objectives of certain programs and activities.
On July 8, 2002, the NSF Director issued Important Notice 127, Implementation of new Grant Proposal Guide Requirements Related to the Broader Impacts Criterion. This Important Notice reinforces the importance of addressing both criteria in the preparation and review of all proposals submitted to NSF. NSF continues to strengthen its internal processes to ensure that both of the merit review criteria are addressed when making funding decisions.
In an effort to increase compliance with these requirements, the January 2002 issuance of the GPG incorporated revised proposal preparation guidelines relating to the development of the Project Summary and Project Description. Chapter II of the GPG specifies that Principal Investigators (PIs) must address both merit review criteria in separate statements within the one-page Project Summary. This chapter also reiterates that broader impacts resulting from the proposed project must be addressed in the Project Description and described as an integral part of the narrative.
Effective October 1, 2002, NSF will return without review proposals that do not separately address both merit review criteria within the Project Summary. It is believed that these changes to NSF proposal preparation and processing guidelines will more clearly articulate the importance of broader impacts to NSF-funded projects.
The two National Science Board approved merit review criteria are listed below (see the Grant Proposal Guide Chapter III.A for further information). The criteria include considerations that help define them. These considerations are suggestions and not all will apply to any given proposal. While proposers must address both merit review criteria, reviewers will be asked to address only those considerations that are relevant to the proposal being considered and for which he/she is qualified to make judgements.
NSF staff will give careful consideration to the following in making funding decisions:
All proposals are carefully reviewed by at least three other persons outside NSF who are experts in the particular field represented by the proposal. Proposals submitted in response to this announcement/solicitation will be reviewed by Ad Hoc Review followed by Panel Review.
Reviewers will be asked to formulate a recommendation to either support or decline each proposal. The Program Officer assigned to manage the proposal's review will consider the advice of reviewers and will formulate a recommendation.
A summary rating and accompanying narrative will be completed and submitted by each reviewer. In all cases, reviews are treated as confidential documents. Verbatim copies of reviews, excluding the names of the reviewers, are sent to the Principal Investigator/Project Director by the Program Director. In addition, the proposer will receive an explanation of the decision to award or decline funding.
NSF is striving to be able to tell applicants whether their proposals have been declined or recommended for funding within six months. The time interval begins on the date of receipt. The interval ends when the Division Director accepts the Program Officer's recommendation.
In all cases, after programmatic approval has been obtained, the proposals recommended for funding will be forwarded to the Division of Grants and Agreements for review of business, financial, and policy implications and the processing and issuance of a grant or other agreement. Proposers are cautioned that only a Grants and Agreements Officer may make commitments, obligations or awards on behalf of NSF or authorize the expenditure of funds. No commitment on the part of NSF should be inferred from technical or budgetary discussions with a NSF Program Officer. A Principal Investigator or organization that makes financial or personnel commitments in the absence of a grant or cooperative agreement signed by the NSF Grants and Agreements Officer does so at their own risk.
Notification of the award is made to the submitting organization by a Grants Officer in the Division of Grants and Agreements. Organizations whose proposals are declined will be advised as promptly as possible by the cognizant NSF Program Division administering the program. Verbatim copies of reviews, not including the identity of the reviewer, will be provided automatically to the Principal Investigator. (See section VI.A. for additional information on the review process.)
An NSF award consists of: (1) the award letter, which includes any special provisions applicable to the award and any numbered amendments thereto; (2) the budget, which indicates the amounts, by categories of expense, on which NSF has based its support (or otherwise communicates any specific approvals or disapprovals of proposed expenditures); (3) the proposal referenced in the award letter; (4) the applicable award conditions, such as Grant General Conditions (NSF-GC-1); * or Federal Demonstration Partnership (FDP) Terms and Conditions * and (5) any announcement or other NSF issuance that may be incorporated by reference in the award letter. Cooperative agreement awards also are administered in accordance with NSF Cooperative Agreement Terms and Conditions (CA-1). Electronic mail notification is the preferred way to transmit NSF awards to organizations that have electronic mail capabilities and have requested such notification from the Division of Grants and Agreements.
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For all multi-year grants (including both standard and continuing grants), the PI must submit an annual project report to the cognizant Program Officer at least 90 days before the end of the current budget period.
Within 90 days after the expiration of an award, the PI also is required to submit a final project report. Failure to provide final technical reports delays NSF review and processing of pending proposals for the PI and all Co-PIs. PIs should examine the formats of the required reports in advance to assure availability of required data.
PIs are required to use NSF's electronic project reporting system, available through FastLane, for preparation and submission of annual and final project reports. This system permits electronic submission and updating of project reports, including information on project participants (individual and organizational), activities and findings, publications, and other specific products and contributions. PIs will not be required to re-enter information previously provided, either with a proposal or in earlier updates using the electronic system.
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Marcia Rawlings, Directorate for Engineering, Division of Bioengineering & Environmental Systems, 565 S, telephone: (703) 292-7956, fax: (703) 292-9098, email: email@example.com
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