Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Funding Opportunity Title

Stem Cells and Alcohol-induced Tissue Injuries (R21)

Activity Code

R21 Exploratory/Developmental Research Grant Award

Announcement Type

New

Related Notices

  • June 3, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same.
  • May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.

Funding Opportunity Announcement (FOA) Number

PA-12-232

Companion Funding Opportunity

PA-12-233, R01 Research Project Grant

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.273  

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) encourages applications to study human and non-human stem cells involved in alcohol-induced tissue injuries. Alcohol abuse is known to cause pathology in a number of organ systems.  Disorders most commonly associated with chronic alcohol consumption include alcoholic liver disease (ALD), pancreatitis, cardiovascular disease, neural damage, endocrine dysfunction, osteoporosis, cancer, and immune dysfunction. The objective of this FOA is to understand the role of stem cells in alcohol-induced tissue damage and recovery, particularly how they are influenced by alcohol metabolism and their role in alcohol-related cancers.

Key Dates
Posted Date

July 10, 2012

Open Date (Earliest Submission Date)

September 16, 2012

Letter of Intent Due Date

Not Applicable.

Application Due Date(s)

Standard dates apply, by 5:00 PM local time of applicant organization.

AIDS Application Due Date(s)

Not Applicable.  

Scientific Merit Review

Standard dates apply. 

Advisory Council Review

Standard dates apply.

Earliest Start Date(s)

Standard dates apply. 

Expiration Date

September 8, 2015

Due Dates for E.O. 12372

Not Applicable.

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (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.


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Table of Contents

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

Stem cells have the potential to develop into many different types of cells, tissues, and organs.  Stem cells are characterized by their capacity of multi-potency of differentiation and self-renewal.  They play a crucial role in many aspects of biology, from embryonic development to tissue repair and maintenance. While stem cells were first described more than a century ago, only in the 1970s were hematopoietic stem cells successfully used in clinic for bone marrow transplantation to treat leukemia. The development of a method to culture human embryonic stem (ES) cells by Thomson and colleagues in 1998 overcame a critical technical barrier. Since that time, many research interests have been focused on ES cells and adult stem cells from several tissues.  Another breakthrough occurred in 2006 when Yamanaka’s laboratory reprogrammed mouse adult cells into pluripotent stem cells by introducing four key transcription factors (Oct3/4, Sox2, c-Myc, and Klf4), which had been known to play an important role in stem cell maintenance.  A year later, the work was reproduced in human skin fibroblasts by Yamanaka’s laboratory using the same combination of genes, and also independently by Thomson’s laboratory by overexpressing OCT3/4, SOX2, NANOG, and LIN28. This new category of stem cells is called induced pluripotent stem (iPS) cells.  The success of reprogramming terminally differentiated human adult cells into iPS cells has offered great opportunities for stem cell research and personalized regenerative medicine.

Alcohol abuse can cause severe damage to the liver, pancreas and other tissues, and can even lead to cancer. Stem/progenitor cells in liver, central nervous system, cardiovascular system, gut, pancreas and maybe in oral/pharyngeal tissues actively participate in the repair and functional recovery process from damage caused by alcohol and its metabolites.  Recent advances in stem cell studies provide new tools to further elucidate mechanisms of alcohol-related pathological conditions, such as alcoholic liver disease, brain degeneration, pancreatitis, and fetal alcohol syndrome. They may also provide us with new therapeutic strategies to treat these disorders.

Liver Injury

The liver is a central organ for homeostasis. Its numerous functions include metabolism, storage, biosynthesis of various biochemical components, and drug detoxification. Liver injury can be caused by viral infection, drugs, excessive alcohol consumption, in addition to many genetic, metabolic and immune disorders. Alcohol toxicity to liver is a function of the duration of alcohol usage, the amount and frequency of intake of alcohol.  Other factors may also play a significant role in mitigating the response, such as a patient's nutrition and/or concomitant viral infection. For instance, drinking too much (more than 5 drinks for men and 4 drinks for women/day) and too often over a long period of time results in alcoholic liver disease (ALD), characterized by fatty liver, steatohepatitis, liver fibrosis, and cirrhosis, and may proceed to hepatocellular carcinoma. Stem cells participate in both tissue pathogenesis and the recovery process in ALD.  In animal experiments of liver transplantation, hepatocytes can clonally expand, suggesting that hepatocytes are themselves functional stem cells. Certain types of severe liver injury, especially when the proliferative capacity of hepatocytes is impaired, can activate a potential stem cell compartment in the intrahepatic biliary tree. These cells are the bipotential oval cells (OC), which could differentiate into hepatocytes and biliary epithelial cells. Bone marrow cells can migrate to the damaged liver and differentiate into myofibroblasts. Myofibroblasts play a central role in the pathogenesis of liver fibrosis, and even in the development of hepatocellular carcinoma.  In alcohol-induced chronic hepatitis, a close correlation has been observed between the degree of progenitor/stem cell activation and the severity of inflammation and fibrosis.  While hepatocytes carry out important tasks such as drug metabolism and maintenance of glucose and lipid levels, OC proliferate following certain types of liver injury.  

Neural Damage

Excessive alcohol intake is associated with structural and functional changes in the adult and developing central nervous system (CNS), manifested by brain atrophy and progressive neurodegeneration, as well as neurodevelopmental disorders such as fetal alcohol syndrome. Recent research demonstrates that neural stem cells (NSCs) divide throughout life and give rise to new neurons. During neurogenesis-proliferation and differentiation of NSC's into neurons and other types of brain cells are heavily regulated by genetic and environmental factors, many of which are associated with excessive alcohol use. Although alcohol causes global changes in the CNS, some brain structures exhibit heightened sensitivity to alcohol effects and/or toxicity. For instance, hippocampal dysfunction and neurodegeneration commonly occur as a result of the neurotoxic effects of alcohol.  NSCs in adult brains, essential for the normal process of neurogenesis, may also have functional significance in alcohol abusers leading to neural damage and alterations in the homeostasis of hippocampal structures.  It is important to understand the contributions of neural stem cells to neurogenesis, including repair and regeneration during abstinence from alcohol and how these are altered in chronic alcohol users. Studying the roles of neural stem cells on hippocampal function may elucidate mechanisms underlying hippocampal dysfunctions, such as learning, memory, and mood disorders in chronic alcoholism.

Cancer

Chronic ethanol consumption may promote carcinogenesis through its metabolite acetaldehyde, through inflammation, increased oxidative stress, or induction of cytochrome P4502E1 (CYP2E1), which can convert pro-carcinogens to carcinogens.  Alcohol can interact with other risk factors, such as viral infection, smoking, obesity and diabetes, in the initiation and progression of cancers.  Furthermore, alcohol may affect the stem cell niche by perturbing many biochemical or signaling pathways known to be important for both stem cells and cancers.  Examples of these pathways include Notch, Hedgehog, Wnt/β-catenin, EGF-like/EGFR/Neu, LIF, TGF-β, integrins, telomerase, SDF-1/CXCR4, prolactin/growth hormone (GH), the IGF-1, Estrogen Receptor (ER), and Stat3 pathways.  Alcohol and its metabolites may interfere with the renewal or differentiation of stem cells or cancer stem cells by affecting one or more of these pathways. 

Other systems

Stem cells also play an important role in both the pathological and recovery processes in pancreatitis, cardiovascular disease, endocrine dysfunction, osteoporosis, and immune dysfunction.

Research Objectives

Recent advances in the field of stem cells have provided great opportunities to understand the underlying mechanisms of alcohol-induced tissue injury and alcohol-related cancers, and to explore new therapeutic strategies for their diagnosis and treatment.  The following examples illustrate areas of interest:

Disease Modeling:

There is a need to generate disease models that resemble diverse human polymorphism in alcohol   metabolizing enzymes. These genetic variant models are of great value to more effectively study the effects of alcohol on stem cell populations and potential pharmacotherapy for alcohol-induced   pathology.  Most of the currently used human cell lines carry genetic and epigenetic artifacts as a result of accommodation to long term tissue culture. Primary human hepatocytes have a limited life span in vitro. Most liver cell lines used today are from malignant tissues or have been genetically modified to gain immortalization. One way might be to explore the phenotypic outcome by iPS cell technology, or other cell reprogramming technologies, to produce create a bank of genetically variable iPS cell lines from normal populations and from well-characterized alcohol-consuming human populations (although iPSCs may also retain epigenetic marks characteristic of the donor cell which could influence their differentiation propensity).  These models can be used to study the interaction of alcohol with genetic, epigenetic, and environmental factors in different genetic models involving Alcohol Dehydrogenase (ADH), Aldehyde Dehydrogenase (ALDH), CYP2E1, and Glutathione S transferase (GST) enzymes. In addition, creating a bank of iPS cell lines from genetically variant patients and normal populations can provide a source for testing new therapeutic drugs on alcohol induced tissue injury in a more effective manner.

It is important to find better approaches for isolating, expanding and reprograming specific populations of stem/progenitor cells in liver and other alcohol related organs. It is also necessary to find animal or chimeric animal models to study human stem cell (including iPS cells) biology, in order to better understand the damaging/recovery process in these specific diseases or disorders

Alcohol's effect on stem cells:

It is important to study alcohol’s effect on endogenous adult stem/progenitor cells, their self-renewal, proliferation, differentiation, transformation, and niche. A full description of the role of adult stem cells in tissue regeneration during alcohol consumption is important for understanding normal and disease-state physiological and pathological processes, and for designing therapeutic approaches. Interaction of exogenous stem cells and endogenous liver stem/progenitor cells in tissue regeneration/repairing of alcohol induced liver injuries, especially the mechanism by which transplanted stem cells integrate into hepatic tissue, are of great importance for clinical use of stem cells.

Characterization of cancer stem cells in alcohol-related cancers:

Investigation of the mechanisms underlying alcohol’s effect on liver stem cells and hepatocellular carcinoma (HCC) including genetic and epigenetic changes is of great importance. Investigation of the roles of polymorphisms of alcohol-related metabolic genes (e.g., ADH, ALDH, CYP2E1, and MTHFR) in liver stem cell and alcohol-related liver cancers along with the interactions of alcohol and its metabolites (especially acetaldehyde) with other risk factors, such as viral infection, smoking and nutritional disorders, in alcohol-related liver cancers are also critical for a full understanding of the constellation of disease presentations seen in chronic alcohol used disorders.

Understand intrinsic and extrinsic signals and signaling pathways regulating stem cell renewal, proliferation, differentiation, and niche.

Investigation of the ability of different types of stem cells (e.g., liver stem/progenitor cells, bone marrow derived stem/progenitor cells, embryonic stem cells and iPS cells) to self-renew, proliferate and differentiate as a function of alcohol use and abuse are encouraged as is the examination of changes in genes and proteins, and signaling pathways regulating these changes, and the development of markers and assays that permit accurate and reliable characterization of alcohol induced specific effect on stem cells.

Section II. Award Information
Funding Instrument

Grant

Application Types Allowed

New
Resubmission
Revisions

The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications.

Award Budget

The combined budget for direct costs for the two year project period may not exceed $275,000. No more than $200,000 may be requested in any single year. Applicants may request direct costs in $25,000 modules, up to the total direct costs limitation of $275,000 for the combined two-year award period.

Award Project Period

Scope of the proposed project should determine the project period. The maximum period is 2 years.

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.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Governments

Other

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 4-6 weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal Investigator(s))

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 PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.   

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Section IV. Application and Submission Information

1. Requesting an Application Package

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.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, 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.

Required and Optional Components

The forms package associated with this FOA includes all applicable components, mandatory and optional.  Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

Page Limitations

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

PHS 398 Research Plan Component

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

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide.

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.

Foreign Institutions

Foreign (non-US) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via 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.

Applicants are responsible for viewing their application 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.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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.  

6. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF 424 (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.

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 SF 424(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.

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 Central Contractor Registration (CCR). 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 by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Section V. Application Review Information

1. Criteria

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.

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

Overall Impact

Reviewers will provide an overall impact/priority 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).

Scored Review Criteria

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.

Significance

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?

Investigator(s)    

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(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation

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?

Approach

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?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

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?

Additional Review Criteria

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/priority score, but will not give separate scores for these items.

Protections for Human Subjects

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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children 

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

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.

Biohazards

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.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable.

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Additional Review Considerations

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/priority score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

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).

Resource Sharing Plans

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) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by the NIAAA, in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications . Following initial peer review, recommended applications will receive a second level of review by the national Advisory Council on Alcohol Abuse and Alcoholism. The following will be considered in making funding decisions:

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD(s)/PI(s) 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.

Section VI. Award Administration Information

1. Award Notices

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 the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

2. Administrative and National Policy Requirements

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

Not Applicable.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) 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. 

Section VII. Agency Contacts

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

Application Submission Contacts

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk (Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Scientific/Research Contact(s)

Peter Gao, M.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-6106
Email: gaozh@mail.nih.gov

Peer Review Contact(s)

Ranga V Srinivas, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-451-2067
Email: gaozh@mail.nih.gov

Financial/Grants Management Contact(s)

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: jfox@mail.nih.gov

Section VIII. Other Information

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.

Authority and Regulations

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 Parts 74 and 92.


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