Grantee Research Project Results
U.S. Environmental Protection Agency
Office of Research and Development
National Center for Environmental Research
Science to Achieve Results (STAR) Program
CLOSED - FOR REFERENCES PURPOSES ONLY
Developing High-Throughput Assays for Predictive Modeling of Reproductive and Developmental Toxicity Modulated Through the Endocrine System or Pertinent Pathways in Humans and Species Relevant to Ecological Risk Assessment
This is the initial announcement of this funding opportunity.
Funding Opportunity Number:
-
Developing High-Throughput Assays for Predictive Modeling of Reproductive and Developmental Toxicity Modulated through the Endocrine System or Pertinent Pathways in Humans and Species Relevant to Ecological Risk Assessment, EPA-G2011-STAR-E1
Early Career Projects: Developing High-Throughput Assays for Predictive Modeling of Reproductive and Developmental Toxicity Modulated through the Endocrine System or Pertinent Pathways in Humans and Species Relevant to Ecological Risk Assessment, EPA-G2011-STAR-E2
Catalog of Federal Domestic Assistance (CFDA) Number: 66.509
Solicitation Opening Date: January 28, 2011
Solicitation Closing Date: May 5, 2011, 11:59:59 pm Eastern Time
Eligibility Contact: James Gentry (gentry.james@epa.gov); phone: 703-347-8093
Electronic Submissions: Ron Josephson (josephson.ron@epa.gov); phone: 703-308-0442
Technical Contact: Pasky Pascual (pascual.pasky@epa.gov); phone: 703-347-8056
Access Standard STAR Forms (https://www.epa.gov/research-grants/funding-opportunities-how-apply-and-required-forms)
View research awarded under previous solicitations (https://cfpub.epa.gov/ncer_abstracts/index.cfm/fuseaction/recipients.archive/)
SUMMARY OF PROGRAM REQUIREMENTS
Synopsis of Program:
The U.S. Environmental Protection Agency (EPA), as part of its Science to Achieve Results (STAR) program, is seeking applications for research in development of high-throughput assays for use in analyzing chemicals or mixtures of chemicals to explain how exposure can be causally related to adverse, apical outcomes related to development and reproduction. These applications can address toxicity modulated by chemical effects on the endocrine system or via a variety of other pathways. Assay systems of interest are those relevant to humans and other species relevant to human health and/or ecological risk assessment.
In addition to regular awards, this solicitation includes the opportunity for early career projects. Please see Section III of this Request for Applications (RFA) for details on the early career eligibility criteria.
Award Information:
Anticipated Type of Award: Grant or cooperative agreement.
Estimated Number of Awards: Approximately nine awards, including one early career award.
Anticipated Funding Amount: Approximately $10.8 million total for all awards
Potential Funding per Award: Up to a total of $1.2 million, including direct and indirect costs, with a maximum duration of three years.
Cost-sharing is not required. Proposals with budgets exceeding the total award limits will not be considered.
Eligibility Information:
Public nonprofit institutions/organizations (includes public institutions of higher education and hospitals) and private nonprofit institutions/organizations (includes private institutions of higher education and hospitals) located in the U.S., state and local governments, Federally Recognized Indian Tribal Governments, and U.S. territories or possessions are eligible to apply.
Special eligibility criteria apply to the early career project portion of this RFA. See full announcement for more details.
Application Materials:
To apply under this solicitation, use the application package available at Grants.gov (for further submission information see Section IV.E. “Submission Instructions and other Submission Requirements”). The necessary forms for submitting a STAR application will be found on the National Center for Environmental Research (NCER) web site, http://epa.govhttps://www.epa.gov/research-grants/funding-opportunities-how-apply-and-required-forms. If your organization is not currently registered with Grants.gov, you need to allow approximately one week to complete the registration process. This registration, and electronic submission of your application, must be performed by an authorized representative of your organization.
If you do not have the technical capability to utilize the Grants.gov application submission process for this solicitation, call 1-800-490-9194 or send a webmail message to https://www.epa.gov/research-grants/forms/contact-us-about-research-grants at least 15 calendar days before the submission deadline to assure timely receipt of alternate submission instructions. In your message provide the funding opportunity number and title of the program, specify that you are requesting alternate submission instructions, and provide a telephone number, fax number, and an email address, if available. Alternate instructions will be e-mailed whenever possible. Any applications submitted through alternate submission methods must comply with all the provisions of this Request for Applications (RFA), including Section IV, and be received by the solicitation closing date identified above.
Agency Contacts:
Eligibility Contact: James Gentry (gentry.james@epa.gov); phone: 703-347-8093
Electronic Submissions: Ron Josephson (josephson.ron@epa.gov); phone: 703-308-0442
Technical Contact: Pasky Pascual (pascual.pasky@epa.gov); phone: 703-347-8056
I. FUNDING OPPORTUNITY DESCRIPTION
A. Introduction
The National Academy of Sciences’ report, Toxicity Testing in the 21st Century: a Vision and a Strategy, proposed that toxicity testing should become less reliant on whole animal tests and eventually rely instead on systems-oriented, computational models, which can be used to screen large numbers of chemicals, based on information from in vitro assays and in vivo biomarkers (NRC, 2007). These data and models would help elucidate pathways that proceed from an initiating molecular event in which a chemical interacts with a biological target(s); continue on through a sequential series of biological processes; and ultimately culminate in an adverse outcome to humans or ecological species. This RFA calls for research in developing high-throughput assays to test for the effects of chemicals on pathways or systems whose perturbation can result in adverse outcomes on development and/or reproduction of humans and other species. The pathways to be tested can be associated with perturbations in either endocrine (e.g., HPG, HPT) or non-endocrine systems. Proposed assays need to be high-throughput (or have the potential to become high throughput) because of the need to test a large number of chemicals and their break-down products that may be environmental contaminants. Assays amenable to testing complex mixtures of chemicals and metabolites are desirable. Given the significant attention in the last several years to assays for direct mammalian estrogen and androgen (EA) receptor interactions, applications should not specifically focus on EA assays. However, proposals extending EA receptor assays to a wide variety of non-mammalian vertebrate species would be responsive, as would comparative studies across mammalian and non-mammalian species. Proposals should primarily focus on assay development and data generation, but the inclusion of computational or modeling tasks that make use of the data generated is also of interest.
In addition to regular awards, this solicitation includes the opportunity for early career projects. Please see Section III of this RFA for details on the early career eligibility criteria.
B. Background
B.1. A Vision of Toxicity Testing and Computational Toxicology
The National Academy of Sciences’ report, Toxicity Testing in the 21st Century: a Vision and a Strategy (NRC, 2007), proposed a vision and a roadmap for toxicology by advocating the use of systems-oriented, data-driven predictive models to explain how toxic chemicals impact human health and the environment. The NRC panel that drafted the report (hereinafter, “the NRC panel”) noted the limitations of traditional toxicity tests that rely primarily on investigating adverse apical endpoints in whole organisms after homogeneous groups of animals are exposed to high doses of a test agent. Not only can these tests be expensive, time-consuming, and reliant on large numbers of animals, but their results raise considerable uncertainties when extrapolating to heterogeneous populations. The NRC panel recommended that toxicity testing should instead build on developments in genomics, cellular biology, bioinformatics and other fields to develop predictive models. Such models would be partially based on the rich volumes of in vitro data derived from pathway-based high-throughput assays. Although the NRC report focused exclusively upon toxicity testing associated with human health assessments, many of the same concerns (and associated recommendations) are applicable to toxicity testing supporting ecological risk assessment (Ankley et al. 2010).
Similarly, Kavlock et al (2008) discuss how physico-chemical properties combined with data generated by high-throughput assays can yield information to help characterize a chemical in terms of its potential for exposure, bioaccumulation, and toxicity. They use the term, “Computational Toxicology,” to refer to the “integration of modern computing and information technology with molecular biology to improve … prioritization of data requirements and risk assessment of chemicals.”
B.2 Adverse outcome pathways in reproductive and developmental systems in humans and other species relevant to human health and/or ecological risk assessment
One of the key ideas in the NRC report is the “toxicity pathway”, which is defined as a cellular response pathway that, when sufficiently perturbed, is expected to result in an adverse health effect (NRC, 2007). Some have suggested this definition narrowly focuses on an organism’s cellular response to chemical exposure (Ankley et al., 2010), and propose an alternative term the “adverse outcome pathway” (AOP), which more explicitly refers to a broader set of pathways that would: (1) proceed from an initiating molecular event in which a chemical interacts with a biological target (e.g., DNA binding, protein oxidation, or receptor/ligand interaction); (2) continue on through a sequential series of biological activities (e.g. gene activation, or altered cellular chemistry or tissue development); and (3) ultimately culminate in an adverse outcome of relevance to human or ecological risk assessors (e.g., mortality, disrupted reproduction, cancer, or extinction). While it may be useful to initially conceive of a toxicity or adverse outcome pathway as a sequential progression of events, it should be noted that each component of this pathway may itself be influenced by other pathways ongoing within the biological system being modeled.
To support pathway-based approaches there is a need to iteratively generate data, then build and test predictive models. What is learned from the models then suggests other types of data to generate. Currently, in the area of developmental and reproductive toxicity, there is a critical need to generate new types of data that can help in the iterative data-model process. Pathways or processes that can lead to reproductive or developmental toxicity have been proposed, but few related high-throughput assays have been developed. The need for high-throughput assays is driven by the large number of man-made chemicals, plus degradation products, in the environment that need to be tested to characterize potential toxicity. The one exception to this lack of high-throughput assays is in the area of estrogen / androgen receptor (EA) interactions, for which assays are widely available for several mammalian species. However, chemicals can behave as selective receptor modulators for the estrogen receptor and other nuclear receptors, likely due to specific coactivator recruitment profiles, and quantitation of this activity and relating it to adverse outcomes remains a significant goal[Safe et al. 2001]. Another major challenge for developmental toxicity in particular is that the adverse outcome may only arise if the chemical interacts with an organism at a particular developmental stage, which implies a particular biological context that is more complex than a single cell type. This in turn implies that appropriate assay systems may involve cell co-cultures, treatment of cells with specific co-factors to mimic developmental-stage-relevant environments, or may require the use of model organisms such as zebrafish.
The literature on pathways involving developmental systems was reviewed by Knudsen and Daston (2010). As an example, they cited work implicating ethanol in teratogenicity in mouse embryos. Based on data from DNA microarrays, this study indicated that ethanol interfered with the development of cell surface receptors and receptors mediating cell adhesion, thereby causing fetal malformation (Green et al. 2007). Ankley et al. (2010) discuss several examples of AOPs, including one impacting the reproductive system of fish (Watanabe, 2009).
There are several critical pathway-related or endocrine-system-related needs in the area of developmental and reproductive toxicity:
- Pathways and their links to developmental or reproductive toxicity apical endpoints need to be researched and documented.
- Assays need to be developed that can identify if a parent chemical or its metabolites can perturb the relevant pathways.
- Assays need to be predictive (adequate sensitivity / specificity) for identifying the pathway(s) that lead to a particular observed whole-animal toxicity.
- Assays need to be high-throughput (or adaptable to a high-throughput format) in order to screen large numbers of chemicals.
- Assays need to be able to be adaptable to a dose-response format in order to put context around the relative potency of a series of active chemicals.
The specific Strategic Goal and Objective from the EPA’s Strategic Plan that relate to this solicitation are:
- Goal 4: Healthy Communities and Ecosystems, Objective 4.4: Enhance Science and Research
The EPA’s Strategic Plan can be found at: http://nepis.epa.gov/Adobe/PDF/P1001IPK.PDF
C. Authority and Regulations
The authority for this RFA and resulting awards is contained in the Toxic Substances Control Act, Section 10, 15 U.S.C. 2609; the Federal Insecticide, Fungicide, and Rodenticide Act, Section 20, 7 U.S.C. 136r; the Safe Drinking Water Act, Section 1442, 42 U.S.C. 300j-1, and the Clean Water Act, Section 104, 33 U.S.C. 1254.
For research with an international aspect, the above statutes are supplemented, as appropriate, by the National Environmental Policy Act, Section 102(2)(F).
Note that a project’s focus is to consist of activities within the statutory terms of EPA’s financial assistance authorities; specifically, the statute(s) listed above. Generally, a project must address the causes, effects, extent, prevention, reduction, and elimination of air pollution, water pollution, solid/hazardous waste pollution, toxic substances control, or pesticide control depending on which statute(s) is listed above. These activities should relate to the gathering or transferring of information or advancing the state of knowledge. Proposals should emphasize this “learning” concept, as opposed to “fixing” an environmental problem via a well-established method. Proposals relating to other topics which are sometimes included within the term “environment” such as recreation, conservation, restoration, protection of wildlife habitats, etc., must describe the relationship of these topics to the statutorily required purpose of pollution prevention and/or control.
Applicable regulations include: 40 CFR Part 30 (Uniform Administrative Requirements for Grants and Agreements with Institutions of Higher Education, Hospitals, and Other Non-Profit Organizations), 40 CFR Part 31 (Uniform Administrative Requirements for Grants and Cooperative Agreements to State and Local Governments) and 40 CFR Part 40 (Research and Demonstration Grants). Applicable OMB Circulars include: OMB Circular A-21 (Cost Principles for Educational Institutions) relocated to 2 CFR Part 220 (http://www.access.gpo.gov/nara/cfr/waisidx_08/2cfr220_08.html), OMB Circular A-87 (Cost Principles for State, Local and Indian Tribal Governments) relocated to 2 CFR Part 225 (http://www.access.gpo.gov/nara/cfr/waisidx_10/2cfr225_10.html), OMB Circular A-102 (Grants and Cooperative Agreements With State and Local Governments), OMB Circular A-110 (Uniform Administrative Requirements for Grants and Other Agreements with Institutions of Higher Education, Hospitals and Other Non-Profit Organizations) relocated to 2 CFR Part 215 (http://www.access.gpo.gov/nara/cfr/waisidx_08/2cfr215_08.html), and OMB Circular A-122 (Cost Principles for Non-Profit Organizations) relocated to 2 CFR Part 230 (http://www.access.gpo.gov/nara/cfr/waisidx_07/2cfr230_07.html).D. Specific Research Areas of Interest/Expected Outputs and Outcomes
Note to applicant: The term “output” means an environmental activity or effort, and associated work products, related to a specific environmental goal(s), (e.g., testing a new methodology), that will be produced or developed over a period of time under the agreement. The term “outcome” means the result, effect, or consequence that will occur from the above activit(ies) that is related to an environmental, behavioral, or health-related objective.
The Agency is soliciting research that proposes to develop novel high-throughput in vitro or model organism-based assays to probe pathways associated with reproductive or developmental toxicity. The focus can be on toxicity in humans and/or species relevant to ecological risk assessment. Relevant pathways may include, but are not restricted to, those involved with the endocrine system. However, proposals to develop assays for mammalian estrogen and androgen receptor interactions should not be submitted, because such assays are already widely available. However, EA-centered proposals for non-mammalian species, or ones that probe cross-species effects would be responsive. Proposals that include the development of computational models using data from the proposed assay systems are also of interest.
As an example of adverse outcomes of interest, fish exposed to wastewater effluent have manifested abnormal reproductive organs, steroid hormone levels, and population male-to-female sex ratios. These abnormalities have been linked to estrogens in the effluent that disrupt the normal operation of the hypothalamic-pituitary-gonadal axis of the fish’s endocrine system (Watanabe et al., 2009). Other adverse outcomes of interest to model include, but are not limited to, reproductive fitness, developmental defects and behavioral abnormalities.
One could propose developing assays that detect direct chemical effects, or responses at the cellular level, e.g. patterns of coactivator recruitment by nuclear receptors, or at higher levels of organization. A computational model could integrate the findings at each of these levels for a common set of chemicals. Another area of interest would be assays that can probe differential chemical effects across life stages, or across populations. The latter might be accomplished using out-bred strains of fish or genetically heterogeneous human cell lines. Yet another area of interest would be the comparison of assay results for a single pathway, but implemented across multiple species. Stem cell-based assays that probe effects of chemicals on differentiation pathways would be of interest. Another area of interest would be assays that compare or differentiate the effects of parent chemicals and their metabolites or degradation products.
The proposal should address all of the following:
- Describe the rationale for the particular assay system in the context of developmental or reproductive toxicity.
- Describe, in particular, how the assay provides information relevant to or anchored against some apical endpoint. This allows, conceptually at least, for one to make a linkage with risk assessment activities.
- Describe how the assays can be scaled to high-throughput, which here means the ability to test large numbers of chemicals in concentration-response mode. For the purpose of this RFA, high-throughput will mean being capable of testing at least 1000 chemicals in dose- or concentration-response format over the duration of the project. However, because of the expense of developing a chemical library of this size, the proposal does not have to include delivery of data on this many unique chemicals. Proposals for assay systems that include aspects of xenobiotic metabolism are of particular interest.
- Describe at least one application of the proposed assay system. This application should address a scientific or risk assessment issue concerning reproductive or developmental toxicity and should involve assaying a set of test chemicals in concentration or concentration-response format in high-throughput mode. This application will serve to test the utility of the assay system to address important toxicological questions. One application type of interest is screening and prioritization of large numbers of untested chemicals. Another would be to provide evidence for or against particular chemicals acting through named pathways, based on combining evidence derived from the new assay data with any existing data on the tested chemicals.
- Describe a quality process for the assay. This should include performance criteria upon which the relevance and responsiveness of the assay can be judged. While this quality process is not equivalent to formal validation, assays should be reproducible, and have acceptable signal-noise characteristics. Relevant criteria can be found in the National Institute of Health’s “Assay Guidance Manual” (available at http://assay.nih.gov/assay). The application’s Research Plan should briefly describe this quality process, while a more detailed description should be provided in the Quality Assurance Statement (see Section IV.B.5.b).
- Describe a plan to test the assay against a defined set of reference compounds either individually or in combinations. The reference compound set should be derived from information in the literature on the pathway or adverse outcome being probed by the proposed assays.
- Describe a data release plan, since all protocols and data produced under this RFA are intended to be made publicly available. The application’s Research Plan should briefly describe this plan, while a more detailed description should be provided in the Data Plan (See Section IV.B.5.c).
Applicants are encouraged to develop computational models that use the data generated to explain how the tested pathway(s) can lead to relevant apical toxicity endpoints.
Outputs expected from the research funded under this RFA will include models based on data derived from high-throughput assays. Outputs will also include reports, presentations, and peer-reviewed journal publications pertaining to the development of high-throughput assays used to predict reproductive and developmental toxicity. Outcomes include furthering the field of toxicity testing by developing assays that can be used to assess the effects of pollutants on the endocrine and reproductive systems of ecologically relevant species.
- Ankley, G. T., R. S. Bennett, et al. (2010). Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment. Environmental Toxicology and Chemistry 29(3): 730-741.
- Green, M. L., A. V. Singh, et al. (2007). Reprogramming of genetic networks during initiation of the fetal alcohol syndrome. Developmental Dynamics 236(2): 613-631.
- Kavlock, R. J., G. Ankley, et al. (2008). Computational toxicology--a state of the science mini review. Toxicological Sciences 103(1): 14-27.
- Watanabe, K. H., Z. Li, et al. (2009). A Computational Model of the Hypothalamic-Pituitary-Gonadal Axis in Male Fathead Minnows Exposed to 17 alpha-Ethinylestradiol and 17 beta-Estradiol. Toxicological Sciences 109(2): 180-192.
- Safe SH, Pallaroni L, et al. (2001) Toxicology of environmental estrogens. Reprod Fertil Dev. 2001;13(4):307-15)
[Reports]
- NRC (National Research Council) (2007). Toxicity Testing in the 21st Century: A Vision and a Strategy. National Academies Press, Washington, DC, 2007A.
[Book Chapter]
- Knudsen, T.B. and Daston, G.P. “Virtual Tissues and Developmental Systems Biology.” In: Comprehensive Toxicology, volume 12, Oxford: Academic Press, 2010, 347–358.
F. Special Requirements
Agency policy and ethical considerations prevent EPA technical staff and managers from providing applicants with information that may create an unfair competitive advantage. Consequently, EPA employees will not review, comment, advise, and/or provide technical assistance to applicants preparing applications in response to EPA RFAs. EPA employees cannot endorse any particular application.
Multiple Investigator applications may be submitted as: (1) a single Lead Principal Investigator (PI) application with Co-PI(s) or (2) a Multiple PI application (with a single Contact PI). If you choose to submit a Multiple PI application, you must follow the specific instructions provided in Sections IV. and V. of this RFA. For further information, please see the EPA Implementation Plan for Policy on Multiple Principal Investigators (http://rbm.nih.gov/toolkit.htm).
Please note: Early career projects will not accommodate a Multiple PI application. Early career projects shall be submitted as a single Lead PI application. Special eligibility criteria apply to the early career portion of this RFA. Please see Section III of this RFA for details on the early career eligibility criteria. The application must include an early career certification (see “Early Career Certification” in Section IV.B.5.d).
Groups of two or more eligible applicants may choose to form a consortium and submit a single application for this assistance agreement. The application must identify which organization will be the recipient of the assistance agreement and which organizations(s) will be subawardees of the recipient.
The application must include a plan (see “Data Plan” in section IV.B.5.c.) to make available to the public all data generated from observations, analyses, or model development (primary data) and any secondary (or existing) data used under an agreement awarded from this RFA. The data must be available in a format and with documentation such that they may be used by others in the scientific community.
It is anticipated that a total of approximately $10.8 million will be awarded under this announcement, depending on the availability of funds and quality of applications received. The EPA anticipates funding approximately nine awards, including one early career award, under this RFA. Requests for amounts in excess of a total of $1.2 million including direct and indirect costs, will not be considered. The total project period requested in an application submitted for this RFA may not exceed three years.
The EPA reserves the right to reject all applications and make no awards, or make fewer awards than anticipated, under this RFA. The EPA reserves the right to make additional awards under this announcement, consistent with Agency policy, if additional funding becomes available after the original selections are made. Any additional selections for awards will be made no later than six months after the original selection decisions.
EPA may award both grants and cooperative agreements under this announcement.
Under a grant, EPA scientists and engineers are not permitted to be substantially involved in the execution of the research. However, EPA encourages interaction between its own laboratory scientists and grant Principal Investigators after the award of an EPA grant for the sole purpose of exchanging information in research areas of common interest that may add value to their respective research activities. This interaction must be incidental to achieving the goals of the research under a grant. Interaction that is “incidental” does not involve resource commitments.
Where appropriate, based on consideration of the nature of the proposed project relative to the EPA’s intramural research program and available resources, the EPA may award cooperative agreements under this announcement. When addressing a research question/problem of common interest, collaborations between EPA scientists and the institution’s principal investigators are permitted under a cooperative agreement. These collaborations may include data and information exchange, providing technical input to experimental design and theoretical development, coordinating extramural research with in-house activities, the refinement of valuation endpoints, and joint authorship of journal articles on these activities. Proposals may not identify EPA cooperators or interactions; specific interactions between EPA’s investigators and those of the prospective recipient for cooperative agreements will be negotiated at the time of award.
A. Eligible Applicants
Public nonprofit institutions/organizations (includes public institutions of higher education and hospitals) and private nonprofit institutions/organizations (includes private institutions of higher education and hospitals) located in the U.S., state and local governments, Federally Recognized Indian Tribal Governments, and U.S. territories or possessions are eligible to apply. Profit-making firms are not eligible to receive assistance agreements from the EPA under this program.
Eligible nonprofit organizations include any organizations that meet the definition of nonprofit in OMB Circular A-122, located at 2 CFR Part 230. However, nonprofit organizations described in Section 501(c) (4) of the Internal Revenue Code that lobby are not eligible to apply.
National laboratories funded by Federal Agencies (Federally-Funded Research and Development Centers, “FFRDCs”) may not apply. FFRDC employees may cooperate or collaborate with eligible applicants within the limits imposed by applicable legislation and regulations. They may participate in planning, conducting, and analyzing the research directed by the applicant, but may not direct projects on behalf of the applicant organization. The institution, organization, or governance receiving the award may provide funds through its assistance agreement from the EPA to an FFRDC for research personnel, supplies, equipment, and other expenses directly related to the research. However, salaries for permanent FFRDC employees may not be provided through this mechanism.
Federal Agencies may not apply. Federal employees are not eligible to serve in a principal leadership role on an assistance agreement, and may not receive salaries or augment their Agency’s appropriations in other ways through awards made under this program.
The applicant institution may enter into an agreement with a Federal Agency to purchase or utilize unique supplies or services unavailable in the private sector to the extent authorized by law. Examples are purchase of satellite data, census data tapes, chemical reference standards, analyses, or use of instrumentation or other facilities not available elsewhere. A written justification for federal involvement must be included in the application. In addition, an appropriate form of assurance that documents the commitment, such as a letter of intent from the Federal Agency involved, should be included.
The early career projects will support research performed by PIs with outstanding promise at the Assistant Professor or equivalent level. Principal investigators from applicant institutions applying for the early career portion of the RFA must meet the following additional eligibility requirements:
- Hold a doctoral degree in a field of science or engineering by the closing date of the RFA;
- Be untenured at the closing date of the RFA;
- By the award date, be employed in a tenure-track position (or tenure-track-equivalent position) as an assistant professor (or equivalent title) at an institution in the U.S., its territories, or possessions. Note: For a position to be considered a tenure-track-equivalent position, it must meet all of the following requirements: (1) the employing department or organization does not offer tenure; (2) the appointment is a continuing appointment; (3) the appointment has substantial educational responsibilities; and (4) the proposed project relates to the employee's career goals and job responsibilities as well as to the goals of the department/organization.
Senior researchers may collaborate in a supporting role for early career projects. Early career applications should not propose significant resources for senior researchers and may not list senior researchers as co-PIs. The application must include an early career verification (see “Early Career Verification” in Section IV.B.5.d ).
Potential applicants who are uncertain of their eligibility should contact James Gentry (gentry.james@epa.gov) in NCER, phone (703) 347-8093.
B. Cost-Sharing
Institutional cost-sharing is not required.
C. Other
Applications must substantially comply with the application submission instructions and requirements set forth in Section IV of this announcement or they will be rejected. In addition, where a page limitation is expressed in Section IV with respect to parts of the application, pages in excess of the page limit will not be reviewed. Applications must be submitted through grants.gov or by other authorized alternate means (see Section IV.E. “Submission Instructions and Other Submission Requirements” for further information) on or before the solicitation closing date and time in Section IV of this announcement or they will be returned to the sender without further consideration. Also, applications exceeding the funding limits or project period term described herein will be returned without review. Further, applications that fail to demonstrate a public purpose of support or stimulation (e.g., by proposing research which primarily benefits a Federal program or provides a service for a Federal agency) will not be funded.
Applications deemed ineligible for funding consideration will be notified within fifteen calendar days of the ineligibility determination.
IV. APPLICATION AND SUBMISSION INFORMATION
Formal instructions for submission through Grants.gov follow in Section E.
A. Internet Address to Request Application Package
Use the application package available at Grants.gov (see Section E. “Submission Instructions and Other Submission Requirements”). Note: With the exception of the current and pending support form (available at http://epa.govhttps://www.epa.gov/research-grants/funding-opportunities-how-apply-and-required-forms), all necessary forms are included in the electronic application package.
An email will be sent by NCER to the Lead/Contact PI and the Administrative Contact (see below) to acknowledge receipt of the application and transmit other important information. The email will be sent from receipt.application@epa.gov; emails to this address will not be accepted. If you do not receive an email acknowledgment within 30 days of the submission closing date, immediately inform the Eligibility Contact shown in this solicitation. Failure to do so may result in your application not being reviewed. See Section E. “Submission Instructions and Other Submission Requirements” for additional information regarding the application receipt acknowledgment.
B. Content and Form of Application Submission
The application is made by submitting the materials described below. Applications must contain all information requested and be submitted in the formats described.
- Standard Form 424
The applicant must complete Standard Form 424. Instructions for completion of the SF424 are included with the form. (However, note that EPA requires that the entire requested dollar amount appear on the 424, not simply the proposed first year expenses.) The form must contain the signature of an authorized representative of the applying organization.
Applicants are required to provide a "Dun and Bradstreet Data Universal Numbering System" (DUNS) number when applying for federal grants or cooperative agreements. Organizations may receive a DUNS number by calling 1-866-705-5711 or by visiting the web site at http://www.dnb.com.
Executive Order 12372, "Intergovernmental Review of Federal Programs," does not apply to the Office of Research and Development's research and training programs unless EPA has determined that the activities that will be carried out under the applicants' proposal (a) require an Environmental Impact Statement (EIS), or (b) do not require an EIS but will be newly initiated at a particular site and require unusual measures to limit the possibility of adverse exposure or hazard to the general public, or (c) have a unique geographic focus and are directly relevant to the governmental responsibilities of a State or local government within that geographic area.
If EPA determines that Executive Order 12372 applies to an applicant's proposal, the applicant must follow the procedures in 40 CFR Part 29. The applicant must notify their state's single point of contact (SPOC). To determine whether their state participates in this process, and how to comply, applicants should consult http://www.whitehouse.gov/omb/grants_spoc/. If an applicant is in a State that does not have a SPOC, or the State has not selected research and development grants for intergovernmental review, the applicant must notify directly affected State, area wide, regional and local entities of its proposal.
EPA will notify the successful applicant(s) if Executive Order 12372 applies to its proposal prior to award.
- Key Contacts
The applicant must complete the "Key Contacts" form found in the Grants.gov application package. An "Additional Key Contacts" form is also available at http://epa.govhttps://www.epa.gov/research-grants/funding-opportunities-how-apply-and-required-forms. The Key Contacts form should also be completed for major sub-agreements (i.e., primary investigators). Do not include information for consultants or other contractors. Please make certain that all contact information is accurate.
For Multiple PI applications: The Additional Key Contacts form must be completed (see Section I.F. for further information). Note: The Contact PI must be affiliated with the institution submitting the application. EPA will direct all communications related to scientific, technical, and budgetary aspects of the project to the Contact PI; however, any information regarding an application will be shared with any PI upon request. The Contact PI is to be listed on the Key Contact Form as the Project Manager/Principal Investigator (the term Project Manager is used on the Grants.gov form, the term Principal Investigator is used on the form located on NCER's web site). For additional PIs, complete the Major Co-Investigator fields and identify PI status next to the name (e.g., "Name: John Smith, Principal Investigator").
- Table of Contents
Provide a list of the major subdivisions of the application indicating the page number on which each section begins.
- Abstract (1 page)
The abstract is a very important document in the review process. Therefore, it is critical that the abstract accurately describes the research being proposed and conveys all the essential elements of the research. Also, the abstracts of applications that receive funding will be posted on the NCER web site.
The abstract should include the information described below (a-h). Examples of abstracts for current grants may be found on the NCER web site.
- Funding Opportunity Title and Number for this proposal.
- Project Title: Use the exact title of your project as it appears in the application. The title must be brief yet represent the major thrust of the project. Because the title will be used by those not familiar with the project, use more commonly understood terminology. Do not use general phrases such as "research on."
- Investigators: For applications with multiple investigators, state whether this is a single Lead PI (with co-PIs) or Multiple PI application (see Section I.F.). For Lead PI applications, list the Lead PI, then the name(s) of each co-PI who will significantly contribute to the project. For Multiple PI applications, list the Contact PI, then the name(s) of each additional PI. Provide a web site URL or an email contact address for additional information.
- Institution: In the same order as the list of investigators, list the name, city and state of each participating university or other applicant institution. The institution applying for assistance must be clearly identified.
- Project Period and Location: Show the proposed project beginning and ending dates and the geographical location(s) where the work will be conducted.
- Project Cost: Show the total dollars requested from the EPA (include direct and indirect costs for all years).
- Project Summary: Provide three subsections addressing: (1) the objectives of the study (including any hypotheses that will be tested), (2) the experimental approach to be used (a description of the proposed project), and (3) the expected results of the project and how it addresses the research needs identified in the solicitation, including the estimated improvement in risk assessment or risk management that will result from successful completion of the proposed work.
- Supplemental Keywords: Without duplicating terms already used in the text of the abstract, list keywords to assist database searchers in finding your research. A list of suggested keywords may be found at: http://epa.govhttps://www.epa.gov/research-grants/funding-opportunities-how-apply-and-required-forms.
- Research Plan, Quality Assurance Statement, Data Plan, Early Career Verification and References
- Research Plan (15 pages)
Applications should focus on a limited number of research objectives that adequately and clearly demonstrate that they meet the RFA requirements. Explicitly state the main hypotheses that you will investigate, the data you will create or use, the analytical tools you will use to investigate these hypotheses or analyze these data, and the results you expect to achieve. Research methods must be clearly stated so that reviewers can evaluate the appropriateness of your approach and the tools you intend to use. A statement such as: "we will evaluate the data using the usual statistical methods" is not specific enough for peer reviewers.
This description must not exceed fifteen (15) consecutively numbered (bottom center), 8.5x11-inch pages of single-spaced, standard 12-point type with 1-inch margins. While these guidelines establish the minimum type size requirements, applicants are advised that readability is of paramount importance and should take precedence in selection of an appropriate font for use in the proposal.
The description must provide the following information:
- Objectives: List the objectives of the proposed research and the hypotheses being tested during the project, and briefly state why the intended research is important and how it fulfills the requirements of the solicitation. This section should also include any background or introductory information that would help explain the objectives of the study. If this application is to expand upon research supported by an existing or former assistance agreement awarded under the STAR program, indicate the number of the agreement and provide a brief report of progress and results achieved under it.
- Approach/Activities: Outline the research design, methods, and techniques that you intend to use in meeting the objectives stated above.
- Expected Results, Benefits, Outputs, and Outcomes: Describe the results you expect to achieve during the project (outputs) and the potential benefits of the results (outcomes). This section should also discuss how the research results will lead to solutions to environmental problems and improve the public's ability to protect the environment and human health. A clear, concise description will help NCER and peer reviewers understand the merits of the research.
- General Project Information: Discuss other information relevant to the potential success of the project. This should include facilities, personnel expertise/experience, project schedules with associated milestones and target dates, proposed management, interactions with other institutions, etc. Applications for multi-investigator projects must identify project management and the functions of each investigator in each team and describe plans to communicate and share data.
- Appendices may be included but must remain within the 15-page limit.
- Quality Assurance Statement (3 pages)
For projects involving environmental data collection or processing, conducting surveys, modeling, method development, or the development of environmental technology (whether hardware-based or via new techniques), provide a Quality Assurance Statement (QAS) regarding the plans for processes that will be used to ensure that the products of the research satisfy the intended project objectives. Follow the guidelines provided below to ensure that the QAS describes a system that complies with ANSI/ASQC E4, Specifications and Guidelines for Quality Systems for Environmental Data Collection and Environmental Technology Programs. Do not exceed three consecutively numbered, 8.5x11-inch pages of single-spaced, standard 12-point type with 1-inch margins.
NOTE: If selected for award, applicants will be expected to provide additional quality assurance documentation.
Address each applicable section below by including the required information, referencing the specific location of the information in the Research Plan, or explaining why the section does not apply to the proposed research. (Not all will apply.)
- Identify the individual who will be responsible for the quality assurance (QA) and quality control (QC) aspects of the research along with a brief description of this person's functions, experience, and authority within the research organization. Describe the organization's general approach for conducting quality research. (QA is a system of management activities to ensure that a process or item is of the type and quality needed for the project. QC is a system of activities that measures the attributes and performance of a process or item against the standards defined in the project documentation to verify that they meet those stated requirements.)
- Discuss project objectives, including quality objectives, any hypotheses to be tested, and the quantitative and/or qualitative procedures that will be used to evaluate the success of the project. Include any plans for peer or other reviews of the study design or analytical methods.
- Address each of the following project elements as applicable:
- Collection of new/primary data:
(Note: In this case the word "sample" is intended to mean any finite part of a statistical population whose properties are studied to gain information about the whole. If certain attributes listed below do not apply to the type of samples to be used in your research, simply explain why those attributes are not applicable.)- Discuss the plan for sample collection and analysis. As applicable, include sample type(s), frequency, locations, sample sizes, sampling procedures, and the criteria for determining acceptable data quality (e.g., precision, accuracy, representativeness, completeness, comparability, or data quality objectives).
- Describe the procedures for the handling and custody of samples including sample collection, identification, preservation, transportation, and storage, and how the accuracy of test measurements will be verified.
- Describe or reference each analytical method to be used, any QA or QC checks or procedures with the associated acceptance criteria, and any procedures that will be used in the calibration and performance evaluation of the analytical instrumentation.
- Discuss the procedures for overall data reduction, analysis, and reporting. Include a description of all statistical methods to make inferences and conclusions, acceptable error rates and/or power, and any statistical software to be used.
- Use of existing/secondary data (i.e., data previously collected for other purposes or from other sources):
- Identify the types of secondary data needed to satisfy the project objectives. Specify requirements relating to the type of data, the age of data, geographical representation, temporal representation, and technological representation, as applicable.
- Specify the source(s) of the secondary data and discuss the rationale for selection.
- Establish a plan to identify the sources of the secondary data in all deliverables/products.
- Specify quality requirements and discuss the appropriateness for their intended use. Accuracy, precision, representativeness, completeness, and comparability need to be addressed, if applicable.
- Describe the procedures for determining the quality of the secondary data.
- Describe the plan for data management/integrity.
- Method development:
(Note: The data collected for use in method development or evaluation should be described in the QAS as per the guidance in section 3A and/or 3B above.)Describe the scope and application of the method, any tests (and measurements) to be conducted to support the method development, the type of instrumentation that will be used and any required instrument conditions (e.g., calibration frequency), planned QC checks and associated criteria (e.g., spikes, replicates, blanks), and tests to verify the method's performance.
- Development or refinement of models:
(Note: The data collected for use in the development or refinement of models should be described in the QAS as per the guidance in section 3A and/or 3B above.)- Discuss the scope and purpose of the model, key assumptions to be made during development/refinement, requirements for code development, and how the model will be documented.
- Discuss verification techniques to ensure the source code implements the model correctly.
- Discuss validation techniques to determine that the model (assumptions and algorithms) captures the essential phenomena with adequate fidelity.
- Discuss plans for long-term maintenance of the model and associated data.
- Development or operation of environmental technology:
(Note: The data collected for use in the development or evaluation of the technology should be described in the QAS as per the guidance in section 3A and/or 3B above.)- Describe the overall purpose and anticipated impact of the technology.
- Describe the technical and quality specifications of each technology component or process that is to be designed, fabricated, constructed, and/or operated.
- Discuss the procedure to be used for documenting and controlling design changes.
- Discuss the procedure to be used for documenting the acceptability of processes and components, and discuss how the technology will be benchmarked and its effectiveness determined.
- Discuss the documentation requirements for operating instructions/guides for maintenance and use of the system(s) and/or process(s).
- Conducting surveys:
(Note: The data to be collected in the survey and any supporting data should be described in the QAS as per the guidance in section 3A and/or 3B above.)
- Collection of new/primary data:
- Research Plan (15 pages)
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.