Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Nanotechnology, once restricted to 'clean rooms,' has become a major industry generating thousands of engineered nanomaterials (ENMs) that are incorporated into everyday products ranging from personal care products to packaging, construction, water filtration, and children's clothes and toys. This widespread production and use of ENMs presents opportunities for unintended human exposure, while their impact on biological systems is not clearly understood. To address these concerns, the NIEHS initiated a nanotechnology environmental health and safety (Nano EHS) program in 2004 and participated in national efforts through the National Nanotechnology Initiative Environmental, Health, and Safety (NNI EHS) Research Strategy (http://www.nano.gov/nni-pca).

The overarching goal of the NIEHS Nano EHS program is to gain a fundamental understanding of the molecular and pathological pathways involved in mediating the response to ENMs. Towards this goal, comprehensive profiles are needed to gain detailed molecular understanding of the interactions between ENM and biological systems. Such knowledge will in turn allow in silico hazard assessment of ENMs and guide the development of benign, next generation, ENMs. The NIEHS Centers for Nanotechnology Health Implications Research (NCNHIR) consortium was formed in 2010 (RFA-ES-09-011) to investigate the correlation between chemical and physical properties with biological endpoints to allow hazard characterization for emerging materials. The research findings from NCNHIR over the past four years studied a small library of ENMs but demonstrated a clear relationship between physicochemical properties and molecular, cellular, and organismal toxicological endpoints. The current FOA builds on the foundation of this earlier effort, expanding our understanding of the interactions between ENM and biological systems using a wider and more representative set of ENMs with a high likelihood of human exposure. The redesigned structure and focus of the NHIR program will include more diverse materials and routes of exposure representing real world scenarios. The cooperative research efforts of this program will enable a linkage between ENM physicochemical properties and cellular and molecular response profiles to predict potential health effects on target and secondary organs associated with diverse routes of exposure to high priority ENMs.

The goals of the NHIR consortium are twofold. One, NHIR will enrich our knowledge base on ENM-biological interactions, by expanding the library of ENMs and physicochemical properties to be investigated; this expansion can be achieved by focusing on specific ENMs with high production and use in consumer products as well as recently emerging (2- and 3-dimensional) materials. Secondly, NHIR will develop a comprehensive biological response profile for these ENMs surveying a wide range of test systems reflecting physiologically relevant models.

This Funding Opportunity Announcement (FOA) solicits research projects that will carry out extensive investigations to evaluate interactions between ENMs and biological systems. An initial set of ENMs to be investigated have been identified with input from the NNI Nanotechnology Health Implications workgroup and will be provided to these research projects by ERCC, a central infrastructure established by the companion FOA, RFA-ES-15-012 "Nanomaterials Health Implications Research (NHIR): Engineered Nanomaterials Resource and Coordination Core (U24)". The ERCC and U01 investigators together will form the NHIR consortium to collaboratively address the goals of this program.

Background and Rationale

There are many challenges and issues that confront Nano EHS, such as the thousands of ENMs used in diverse products, lack of life-cycle analysis of nanoenabled products, proprietary issues with regard to the physicochemical properties of ENMs in products, and lack of exposure data. It's impossible to generate comprehensive toxicity profiles for all of these ENMs, but a systematic evaluation of a select set of common physicochemical properties and types of ENMs used, may guide in hazard ranking and categorization. To continue our proactive approach to address immediate Nano EHS issues, and to prioritize effort on ENMs that are already in the market with potential for human exposure, we solicited input from regulatory agency partners of NNI on ENMs to be investigated by the NHIR consortium. In addition, the NIEHS also identified the need to understand potential biological interactions of emerging 2D- and 3D- nanomaterials that are expected to enter the marketplace soon.

In addition to carrying out the research proposed, the U01 investigators have opportunities to collaboratively work with ERCC in developing assays and analytical tools for in situ characterization of ENMs in biological samples as needed.

Objectives

The NIEHS Centers for Nanotechnology Health Implications Research (NCNHIR) consortium http://www.niehs.nih.gov/research/supported/dert/programs/nanohealth/index.cfm that is concluding in 2015 was the first effort towards gaining comprehensive and systematic understanding on the ENMs-biological interactions as dictated by ENM physicochemical properties. In this effort as a consortium investigators generated biological response profiles for silver nanomaterials of two different sizes and surface coatings as well as preliminary efforts investigating multi wall carbon nanotubes (MWCNTs) of different aspect ratio and surface chemistry. This FOA will extend these earlier efforts by characterizing biological response profiles for a larger, carefully selected set of ENMs including nanomaterials that are already in market or will be in the near future.

The ENMs listed below were pre-identified based on the needs of regulatory agency members of NNI. All investigators of the NHIR consortium will carry out investigations using only the ENMs from this library and any additional ENMs or physicochemical modifications to some of these ENMs may be considered by the consortium as needs evolve over time.

All materials will be provided by the ERCC in a range of sizes, shapes, and surface chemistries:

• Metals: silver, gold, aluminum, cobalt, copper, iron, molybdenum, zinc, and manganese;
• Metal oxides: aluminum trioxide, cerium trioxide, cobalt oxide, copper oxide, iron oxide, silicon dioxide, titanium dioxide, zinc oxide;
• Carbon nanotubes: SWCNTs, MWCNTs;
• 2D- and 3-D ENMS: Graphene, graphane, silicine, germanane including representative transition metal oxides, halides, and phosphates;
• Metal-metal conjugates; and
• Cellulose.

The objectives of NHIR Consortium are to:

• Produce comprehensive biological response profiles for diverse ENMs using in vitro and in vivo models and relevant routes of exposure to gain understanding on potential molecular, biochemical and pathophysiological alterations at target and secondary organs; and
• Work collaboratively, as appropriate, to integrate efforts and capitalize from other model systems and expertise of NHIR to enrich our knowledge base on ENM-biological interactions.

Applications to this FOA should propose to investigate how physicochemical properties of ENMs dictate biological response profiles at the molecular, cellular, or organ level using physiologically relevant models and routes of exposures. The research applications are also encouraged to include independent investigations into the contributions of factors such as gender, age, physiological status, genetics, species specificity and pre-existing disease conditions in understanding their influence on biological response. Experimental systems can include, but are not limited to:

• High throughput approaches to identify acute response profiles at multiple time points; these systems should also incorporate cell and tissue variability;
• Omics approaches to identify effects on biological pathways and systems including inflammatory, oxidative stress, or fibrogenic pathways;
• Immunogenic, mutagenic, and carcinogenic potential of ENMs using sub-chronic and chronic exposures;
• Cell integrity and cell-cell communications including autocrine, paracrine and endocrine effects;
• Effects on cellular organelles including cross-talk between cellular compartments;
• Inflammasome activation;
• Perturbations in the endogenous microbiome;
• Effects on bacterial or viral infectivity; or
• Absorption, distribution, metabolism and excretion.

Earlier efforts through the NCNHIR consortium were focused on exposure to ENMs through pulmonary route and this FOA strongly encourages investigations using other routes of exposures such as:

• Dermal,
• Oral,
• Ocular,
• Pulmonary (inhalation only), or
• Intravenous.

Note: Research projects that propose pulmonary route of exposure (using bolus dose administration methods - intratracheal and oropharyngeal aspiration) are of low programmatic priority and will not be considered responsive to this FOA.

Investigators in NHIR will be expected to participate in a collaborative research network that seeks to complement multidisciplinary expertise to gain comprehensive understanding of the interactions between ENM and biological systems across diverse organs (target or secondary) to identify common and unique biological responses and outcomes. This can include, for instance, direct collaborations between members of the consortium to combine expertise and model systems; flexibility to address joint hypotheses; or meta-analysis of data across systems (in vitro and in vivo), exposures, and organs as appropriate.

In addition to the required cooperative activities detailed below in the Cooperative Agreement Terms and Conditions, the NIEHS expects, and as appropriate will provide supplementary support for, collaborative activities among and between the consortium members to promote research efforts to gain new understanding of the interactions between ENM and biological systems. Such collaborative activities may include:

• Integrating data across projects (using data deposited in the CEBS database) to jointly address new hypotheses such as common response pathways across material properties/cell types/tissues/animal models;
• Collaborating with consortium investigators to develop new sample preparation protocols and testing strategies to accommodate new materials and diverse routes of exposures; and
• Developing novel tools and methods for characterization of ENMs in situ in biological samples;

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses

Governments

• State Governments
• County Governments
• Eligible Agencies of the Federal Government

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed..

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Dr. Leroy Worth
Telephone: 919-541-0670
Fax: 301-480-3722
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy: Address the main objective of NHIR consortium, which is to generate comprehensive and systematic biological response profiles for select ENMs to be provided by ERCC to the investigators.

As part of this section describe the following elements:

• How the proposed research project will meet the general program objectives of the NHIR consortium and will generate comprehensive toxicity profiles for diverse ENMs;
• Plans for self-evaluation and research project performance monitoring 

Applicants must discuss an operational plan detailing their willingness to participate as a member of NHIR consortium, which will require coordination of selection and prioritization of ENMs for further research, timeline for proposed investigations, development of protocols for specific routes of exposures, and tools for in situ characterization as needed, and regular submission of data and supporting documentation to the Nano-CEBS Database and scientific collaborations as appropriate.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan and should include addressing depositing this information into the NIEHS Chemical Effects on Biological Systems Database (CEBS), consistent with achieving the goals of this program.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. <Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NIEHS, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NIEHS Review Branch by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Does the proposed research plan adequately address the goals of the NHIR consortium? Does the project adequately outline a plan to systematically assess the biological response profile for diverse ENMs?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Do the investigators have a track record of achievement in investigating and generating biological response phenotype for diverse ENMs? Do the investigators demonstrate expertise or experience in working and contributing to the success of a multi-institutional consortium?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Does the application propose novel concepts and strategies to support NHIR consortium research? Are the concepts and strategies or methodology novel to nanotoxicology?

Does the application propose how their research project will open new areas of opportunity for consortium members?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? 

Are the overall design, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the NHIR consortium research activities? Does the application propose an adequate plan and flexibility to work with ENMs to be prioritized by the NHIR consortium steering committee?

Does the proposed strategy include appropriate methods and alternate plans to investigate diverse types of ENMs and accommodate the demands of the NHIR? Is the proposed research strategy likely to achieve success? Are the plans for monitoring performance of research projects adequate?

Have the applicants developed an operational plan for participation at steering committee, virtual, and in-person meetings?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Will the institutional environment in which the research project will be carried out contribute to the probability of success in facilitating the NHIR consortium research? Are the equipment and facilities in place to start the work at the time of the award? Will the infrastructure and instrumentation facilities be able to deliver reliable high standard comprehensive toxicological profiles for diverse ENMs?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Not Applicable

Not Applicable

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Not Applicable

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Institute of Environmental Health Sciences , in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• Will undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Environmental Health Sciences Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. 

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) of the U01 research projects will have the primary responsibility for:

The PD/PI (or multiple PDs/PIs, if applicable) will have primary authority and responsibility to define objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of projects conducted. The PD/PI assumes responsibility and accountability to the applicant organization officials and to the NIH for the performance and proper conduct of research in accordance with terms and conditions of the award.

All Program Directors/Principal Investigator(s) of the NHIR Consortium will have the primary responsibility for:

• Overseeing the budget and activities of the award, as detailed, above.
• Collaborate with other NHIR consortium investigators and NIH Staff, as appropriate, in the design and conduct of proposed research, analysis of data, and reporting of results of research undertaken.  This includes, but is not limited to:
• Providing research strategy to accommodate the biological response assessment of diverse ENMs to be provided by ERCC in a timely fashion.
• Collaboratively develop protocols, analytical methods for in situ characterization of ENMs in cell/tissues/systems of interest.
• Sharing data, protocols and other research resources generated through the NHIR Consortium as appropriate.
• romoting and participating in scientific collaboration across NHIR Consortium.
• Participating in appropriate Working Groups to support collaborative efforts across the NHIR Consortium.
• Interacting and complying with requests for information from the NHIR Consortium Steering Committee and other sub-committees as appropriate.
• Participating in the annual PD/PI scientific meetings, steering committee and other and conference calls organized by the NHIR Consortium as needed.
• Cooperating in the program evaluation activities.
• Accepting and implementing all scientific, practical, and policy decisions approved by the NHIR Consortium Steering Committee to the extent consistent with applicable grant regulations.
• Serving on the NHIR Consortium Steering Committee (for details, see "Areas of Joint Responsibility" below).
• Providing information to the NIH Program Directors and Project Scientists concerning progress by submitting annual progress reports in a standard format.
• Complying with federal regulatory requirements, including but not limited to those relating to human subjects protections, informed consent, and reporting of adverse events.

The PD(s)/PI(s) of the ERCC (RFA-ES-15-012) will have the primary responsibility for:

The PD/PI (or multiple PDs/PIs, if applicable) will have primary authority and responsibility to define objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of projects conducted. The PD/PI assumes responsibility and accountability to the applicant organization officials and to the NIH for the performance and proper conduct of ERCC research in accordance with terms and conditions of the award.

All Program Director(s)/Principal Investigator(s) of the ERCC will have the primary responsibility for:

• Overseeing the budget and activities of the award, as detailed, above.
• Providing appropriate timeline and schedule for procurement/synthesis and comprehensive characterization of ENMs.
• Sharing ENMs characterization data, protocols, and other research resources generated through the ERCC with NHIR U01 investigators and deposition of characterization data to CEBS in a timely fashion as appropriate.
• Promoting and coordinating collaborative research across NHIR consortium investigators and NIH Staff, as appropriate, in the design and development of analytical methods for in situ characterization of ENMs, protocols for dispersion of ENMs in diverse biological media, etc. as needed.
• Providing logistical support for the conduct of steering committee conference calls, virtual and face to face meetings of NHIR consortium including generation, review and sharing of meeting minutes in a timely fashion.
• Interacting and complying with requests for information from the NHIR Steering Committee and other sub-committees as appropriate.
• Cooperating in the program evaluation activities.
• Accepting and implementing all scientific, practical, and policy decisions approved by the NHIR consortium Steering Committee to the extent consistent with applicable grant regulations.
• Serving on the NHIR consortium Steering Committee (for details, see "Areas of Joint Responsibility" below).
• Providing information to the NIH Program Directors and Project Scientists concerning progress by submitting annual progress reports in a standard format.
• Complying with federal regulatory requirements, including but not limited to those relating to human subjects protections, informed consent, and reporting of adverse events.

NIH staff has substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
One or more NIEHS Program Directors will be substantially involved in the NHIR consortium as NIH Project Scientists. NIH Project Scientists will have substantial scientific and programmatic involvement that is above and beyond the normal stewardship role in awards.  NIEHS Project Scientist(s) will have the following responsibilities to all NHIR Consortium awardees:

• Have substantial involvement to guide, coordinate, and participate in the conduct of the NHIR consortium activities.
• Attend and participate in all Steering Committee and subcommittee meetings of the NHIR.
• Coordinate and facilitate the interactions among the awardees under this cooperative agreement.
• Serve as a liaison between the Steering Committee, the NHIR, the NIH and other federal agencies as needed.
• Facilitate and coordinate the exchange of information and interactions between Consortium awardees to support collaborative efforts.
• Participate in organizing and coordinating NHIR Scientific meetings as required.
• Advise on the design of research activities, availability of resources, and/or management and technical performance of projects, as appropriate.
• Participate as collaborators to the NHIR U01 investigators in some shared activities, as appropriate.
• Evaluate the adherence of ERCC awardee to any approved data sharing plans or intellectual property plans.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The NIH reserves the right to adjust funding, withhold, suspend, or terminate the support to ERCC awardee institution(s) that are unable to meet the performance requirements set forth in these Terms and Conditions of Award, or significantly change the level of performance. The NIH Program Official will be responsible for monitoring the level of performance and making recommendations for any corrective actions.

Areas of Joint Responsibility include:

A Steering Committee will serve as the governing board for the NHIR Consortium.

The NHIR Steering Committee will have primary responsibility for:

• Overseeing the overall organization of the NHIR Consortium for reviewing its research goals. Evaluating the adherence of NHIR investigators to any approved data sharing plans or intellectual property plans.
• Developing the appropriate strategy for exchange of materials, protocols, novel research findings, etc. across the NHIR Consortium.
• Making recommendations for re-directing the Consortium's focus in order to accommodate new scientific opportunities and directions.
• Sharing and reviewing annual progress of NHIR Consortium investigators.
• The Steering Committee will be comprised of the following voting members:
• The Principal investigators of ERCC and Principal Investigators of the U01 research projects (RFA-ES-15-013), who will have one vote.
• The NIEHS Program Director will have one vote.
• The NIH Project Scientist and other staff members may participate in Steering Committee meetings as non-voting members.
• A Steering Committee Chair will be elected every twelve months from amongst the Steering Committee members by the committee. An individual may continue serving as Chair for more than one year if all committee members agree. NIH staff cannot serve as Steering Committee Chair.  
• In the event that PD(s)/PI(s) cannot agree on critical aspects of the Consortium, such as prioritizing ENMs for investigations, then the Steering Committee, in consultation with NIH Program Staff, will vote on a recommendation for how to proceed. NIEHS Staff will have final authority to implement proposed recommendations.  All activities must comply with NIH, DHHS, and Federal Guidelines.
• Other guidelines for the Steering Committee, such as a quorum and frequency and type of meetings (in-person, remote), will be determined at its initial meeting. It is anticipated that the Steering Committee will meet at least once per month by teleconference.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Srikanth Nadadur, PhD
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 919-541-5327
Email: [email protected]

David Balshaw, PhD
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 919-541-2448
Email: [email protected]

Leroy Worth, PhD
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 919-541-0670
Email: [email protected]

Lisa Archer Edwards, MBA
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 919-541-0751
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.