Department
of Health and Human Services
Participating
Organizations
National Institutes of Health (NIH) (http://www.nih.gov)
Components of Participating Organizations
National Institute of Alcohol Abuse and
Alcoholism (NIAAA) ( http://www.niaaa.nih.gov )
Title: Animal Models of Endophenotypes and Intermediate Phenotypes
for Alcohol Related Behaviors (RO1)
Announcement Type
New
NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide
APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.
This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).
A registration process is necessary before submission and applicants are highly encouraged to start the process at least four weeks prior to the grant submission date. See Section IV.
Request for Applications (RFA) Number: RFA-AA-07-013
Catalog of Federal Domestic Assistance Number(s)
93.273
Key Dates
Release/Posted
Date: January 5, 2007
Opening Date: March 25, 2007 (Earliest
date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): March 25, 2007
NOTE:
On time submission requires that applications be successfully submitted to
Grants.gov no later than 5:00 p.m. local time (of the applicant
institution/organization).
Application Receipt Date: April 25, 2007
Peer Review Date(s): July/August 2007
Council Review Date(s): August 2007
Earliest Anticipated Start
Date(s): September 15, 2007
Additional Information To Be
Available Date (Activation Date): Not Applicable
Expiration
Date: April 26, 2007
Due Dates for E.O. 12372
Not Applicable
Additional
Overview Content
Executive Summary
Table of Contents
Part I Overview Information
Part II Full Text of Announcement
Section I. Funding Opportunity
Description
1. Research Objectives
Section II. Award Information
1. Mechanism of Support
2. Funds Available
Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2. Cost Sharing or Matching
3. Other-Special Eligibility Criteria
Section
IV. Application and Submission Information
1. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Submission, Review, and
Anticipated Start Dates
1. Letter of Intent
B. Submitting an Application
Electronically to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements
Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Sharing Research Data
D. Sharing Research Resources
3. Anticipated Announcement and Award Dates
Section VI. Award Administration
Information
1. Award Notices
2. Administrative and National Policy Requirements
3. Reporting
Section VII. Agency Contacts
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/Grants Management Contact(s)
Section VIII. Other Information
- Required Federal Citations
Part II
- Full Text of Announcement
Section I. Funding Opportunity Description
1. Research Objectives
Background
Alcohol dependence is a complex disorder that is a result of interactions between genetic and environmental factors. Twins and adoption studies have indicated that the genetic contribution to the risk of alcohol dependence is about 40-60%. Several genes or allelic variations including GABRA2, CHRM2, OPRM1, SERT, NPY, ADH4 and ADH7 have been identified to confer risk for alcohol dependence and related comorbid disorders. The effort to identify genes for alcohol dependence in humans has been thus far limited due, in part, to the heterogeneity of phenotypes associated with clinical diagnostic criteria. Approaches employing endophenotypes and intermediate phenotypes present alternative strategies for this effort. We define endophenotypes as innate biological traits that are highly heritable, but less complex and more proximal to gene function than clinical phenotypes. Examples of endophenotypes include altered electrophysiological characteristics, temperament, and gene expression patterns. For example, the GABRA2 and CHRM2 genes have been linked to the risk for alcohol dependence as well as related comorbid disorders through neurophysiological endophenotypes such as altered EEG and ERP characteristics. Intermediate phenotypes are defined as host responses to alcohol such as sensitivity, tolerance or withdrawal severity that can facilitate the development of alcohol dependence. Using fMRI, the COMT gene has been shown to be associated with altered cognitive function and prefrontal cortex response, and serves as an intermediate phenotype for late-onset alcoholism, schizophrenia as well as anxiety-related behaviors. These studies demonstrate that studying endophenotypes or intermediate phenotypes is a successful approach in the search of genetic underpinnings of alcohol dependence.
Animal models offer numerous advantages over humans for studying genetic and environmental influences and mechanisms since human studies are restricted by technical limitations and ethical issues. The use of endophenotypes and intermediate phenotypes can also be extended to animal models. Endophenotypes and intermediate phenotypes recognized in human clinical studies can be characterized in animal models and the underlying genetic influences and mechanisms can be identified and correlated with human observations. For example, reduced sensitivity to alcohol and withdrawal severity in humans is correlated with greater risk for alcohol dependence. Mice with a knock out of the NPY, NPY Y1 or Drd2 gene show decreased alcohol sensitivity and increased alcohol consumption. Some of these same genes have been identified in human studies through gene linkage or association studies. Mice with a knock out of the CRF2, FYN or DBH gene demonstrated increased alcohol sensitivity and decreased alcohol consumption.
About 100 genes have been studied for their responses to ethanol using animal models genetically modified by techniques such as gene knock-out, knock-in or transgenic gene expression (Crabbe et al. 2006). However, limited data exists on the endophenotypes or intermediate phenotypes that are shared among these animal models and alcohol dependent persons. Characterizing these animal models for behavioral or physiological phenotypes associated with human alcoholism has the potential to promote the identification of candidate genes and mechanisms associated with risk for alcohol dependence in humans with similar endophenotypes. In addition to genetically modified animals, inbred strains (e.g., D2, B6, etc.), recombinant inbred strains (e.g., B x D, LL x SS, etc.) and selectively bred lines (e.g., P and NP, HAD and LAD, HAP and LAP) are employed in alcohol research. Again, limited data exist on the endophenotypes or intermediate phenotypes that are shared among these animal models and alcohol dependent humans. Subsequent genetic analysis could provide evidence for the common genetic influences on endophenotypes and alcohol dependence applicable to both animal models and humans. In sum, animal models offer an opportunity to more readily identify genes that contribute to risk for alcohol dependence in humans.
Tests in animal models have been developed to assess behavioral and physiological traits that may relate to facets of alcohol dependence. In rodents, anxiety, a behavioral trait with some association to increased risk for alcoholism, is inferred from reduced exploratory behavior and increased defecation and urination in the elevated plus maze, open field apparatus or light/dark test box and defensive burying of a novel object (Cryan & Holmes, 2005). Other, less frequently used tests include shock avoidance and conditioned suppression paradigms. Depression-like states and traits are assessed through stress-induced coping strategies as reflected by immobility in the forced swim test, or in the tail suspension test (Jacobson & Cryan, 2006). Other, less frequently used measures include anhedonia following stress or other manipulations. Bilateral olfactory bulbectomy produces behavioral and physiological changes that resemble characteristics of patients with major depression. The validity of this latter model is supported by the finding that many of these changes are reversed by chronic antidepressant treatment (Song & Leonard, 2005). In contrast to studies in alcohol dependent humans, published animal research using selective breeding and targeted mutation approaches only partially supports an association between anxiety and depression related measures and alcohol drinking. Possible reasons for this discrepancy are discussed below. In addition, some rodent lines displaying characteristics of anxiety or depression have not been tested for alcohol effects. These include mice with null mutations of genes encoding GABA(A) gamma2 receptor subunits, glutamate decarboxylase 65, catechol-O-methyltransferase, dopamine D4 receptor, and p11(S100A10) protein, and rats selectively-bred for low swim-test activity (West & Weiss, 1997).
Alcohol dependence also shares a common genetic etiology with externalizing spectrum disorders such as antisocial personality and conduct disorder. Externalizing disorders are characterized by impulsivity, irritability, and aggression. In animals, impulsivity is typically assessed in operant tasks requiring the withholding of a behavioral response (e.g., go/no-go discrimination tasks), and in choice tasks requiring choices between large, delayed rewards and small immediate rewards. Novelty-seeking, another manifestation of behavioral disinhibition, is a heritable moderator of familial risk for alcohol dependence (Grucza et al. 2006). In genetically heterogeneous rats, exploration in a novel environment was positively correlated with motivation to drink alcohol; whether genetic variation contributed to this association was not examined (Nadal et al. 2002). Relative to other traits such as alcohol sensitivity or anxiety/depression behavior, the relationship between genetic variation in externalizing traits and alcohol drinking has received little attention in animal studies. Alcohol drinking and impulsivity, as measured by a signaled nose-poke task, were correlated across 13 inbred mouse strains (Logue et al, 1998). In addition, mice with a nonfunctional mutation of the protein kinase C gamma gene drank more alcohol and were more impulsive on a signaled nose-poke task relative to wildtype. In selective breeding studies, Spontaneously Hypertensive Rats exhibit impulsive behavior in choice tasks and drink more alcohol than the inbred, anxious, Lewis line (Da Silva et al. 2005). Breeding for low anxiety may select for a pathological absence of anxiety observed in some externalizing psychiatric disorders and could also predispose alcohol drinking. Hence, selectively-bred Low Anxiety Behavior rats drank more alcohol than the complementary High Anxiety Behavior line and showed a robust alcohol deprivation effect (Henniger et al. 2002). Other novelty-seeking, impulsivity, and aggression models await testing for alcohol-related measures including rats selectively bred for low ultrasonic vocalization (Brunelli, 2005), mice selectively bred for short attack latency in the resident-intruder paradigm (van Oortmerssen et al. 1981), and mice selectively bred for high exploratory behavior (Kliethermes & Crabbe, 2006).
A potential problem for interpreting some of the forgoing studies is the absence of a phenotypic norm. Breeding studies select for extremes, but do not typically include randomly bred control lines in most cases. Another problem is that studies were typically performed using one or two complementary lines, thereby introducing considerable variability in testing methods across studies. In addition, most animal studies measured a single alcohol effect, usually two bottle choice drinking. This renders an incomplete characterization. Two bottle choice drinking does not predict outcomes of tests that model key features of alcohol dependence such as the motivation to work for alcohol, increased drinking following alcohol exposure, stress-induced drinking, reinstatement of alcohol seeking, or dependence-induced drinking. A further limitation of existing animal studies is that most use only a single test (e.g., elevated plus maze) to represent a complex construct such as anxiety or novelty seeking; however, a single test only partially measures the broader constructs and may also be influenced by other states (e.g., motivation) or traits (e.g., activity). Performance on multiple tests purported to measure alcohol-sensitivity or novelty-seeking is not correlated across genotype, suggesting these are genotypically complex traits not amenable to measurement by a single test (Kliethermes & Crabbe, 2006). In several inbred mouse strains, postnatal maternal separation produced inconsistent effects on multiple measures of anxiety and depression-like behavior (Millstein & Holmes, 2006). In light of these observations, genetically influenced traits relevant to human alcohol dependence (e.g., anxiety, depression, impulsivity, novelty seeking, and aggression) need to be characterized in existing animal models using comprehensive testing methods. This may require the development of standardized test batteries or the use of appropriate multivariate test environments such as the Concentric Square Field (Meyerson et al. 2005). In this context, we encourage the use of statistical approaches (e.g., factor analysis) to identify specific components of broader constructs as they relate to measures of alcohol action. This approach has been used successfully to compare components of elevated plus maze behavior in adolescent and adult rats (Doremus et al. 2006), to identify heritable clusters of fearful-anxious behaviors in rhesus monkeys (Williamson et al. 2003), and to identify parameters of emotionality and anxiety associated with alcohol drinking across several alcohol preferring and non-preferring rat strains (Overstreet et al. 1997). As a complement to behavioral testing, we also encourage the measurement of purported physiological indices of internalizing and externalizing traits such as P300 amplitude, or brain p11 (S100A10) protein levels.
Objectives and Scope
The goal of this FOA is to determine the contribution of genetically-determined traits associated with human alcoholism (i.e., endophenotypes) to initial alcohol response (intermediate phenotype) and the subsequent development of alcohol dependence. This FOA solicits proposals to: (1) comprehensively test traits relevant to human alcoholism in genetic models, and (2) evaluate alcohol actions in these models under conditions that reflect the progression from inexperienced to compulsive alcohol use. Selection of species and measures should be justified for their relevance to conditions related to alcohol dependence.
Example of research areas and approaches relevant to this FOA include, but are not limited to:
References
Brunelli SA. (2005) Selective breeding for an infant phenotype: rat pup ultrasonic vocalization(USV).Behav Genet. 35:53-65.
Cryan JF, Holmes A.(2005), The ascent of mouse: advances in modeling human depression and anxiety. Nat Rev Drug Discov 4:775-90.
Da Silva GE, Vendruscolo LF, Takahashi RN. (2005) Effects of ethanol on locomotor and anxiety-like behaviors and the acquisition of ethanol intake in Lewis and spontaneously hypertensive rats. Life Sci.77:693-706.
Doremus TL, Varlinskaya EI, Spear LP. (2006) Factor analysis of elevated plus-maze behavior in adolescent and adult rats. Pharmacol Biochem Behav. 83:570-7.
Grucza RA, et al. (2006) Novelty seeking as a moderator of familial risk for alcohol dependence. Alcohol Clin Exp Res. 30:1176-83.
Henniger MS, Spanagel R, Wigger A, Landgraf R, Holter SM. (2002) Alcohol self-administration in two rat lines selectively bred for extremes in anxiety-related behavior. Neuropsychopharmacology. 26(6):729-36.
Jacobson LH, Cryan JF. (2006) Feeling Strained? Influence of Genetic Background on Depression-Related Behavior in Mice: A Review. Behav Genet. 2006 Sep 23; [Epub ahead of print]
Kliethermes CL, Crabbe JC. (2006) Genetic independence of mouse measures of some aspects of novelty seeking. Proc Natl Acad Sci U S A. 103:5018-23.
Logue SF, Swartz RJ, Wehner JM. (1998) Genetic correlation between performance on an appetitive-signaled nosepoke task and voluntary ethanol consumption. Alcohol Clin Exp Res. 22:1912-20.
Meyerson BJ, Augustsson H, Berg M, Roman E. (2005) The Concentric Square Field: a multivariate test arena for analysis of explorative strategies. Behav Brain Res. 168:100-13.
Millstein RA, Holmes A. (2006) Effects of repeated maternal separation on anxiety- and depression-related phenotypes in different mouse strains. Neurosci Biobehav Rev. Sep 1; [Epub ahead of print]
Nadal R, Armario A, Janak PH. (2002) Positive relationship between activity in a novel environment and operant ethanol self-administration in rats. Psychopharmacology 162:333-8.
Overstreet DH et al. (1997) Behavioral similarities and differences among alcohol-preferring and -nonpreferring rats: confirmation by factor analysis and extension to additional groups. Alcohol Clin Exp Res. 21:840-8.
Patrick CJ et al. (2006 P300 amplitude as an indicator of externalizing in adolescent males. Psychophysiology 43:84-92.
Song C, Leonard BE. (2005) The olfactory bulbectomised rat as a model of depression. Neurosci Biobehav Rev. 2005;29(4-5):627-47.
van Oortmerssen GA, Bakker TC (1981) Artificial selection for short and long attack latencies in wild Mus musculus domesticus, Behav Genet 11:115–126.
Wang JC,et al.(2004) Evidence of common and specific genetic effects: association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence and major depressive syndrome. Hum Mol Genet. 13(17):1903-11.
West CH, Weiss JM. (1998) Effects of antidepressant drugs on rats bred for low activity in the swim test. Pharmacol Biochem Behav. 61:67-79.
Williamson DE et al. (2003) Heritability of fearful-anxious endophenotypes in infant rhesus macaques: a preliminary report. Biol Psychiatry. 53:284-91.
See Section VIII, Other Information - Required Federal
Citations, for policies related to this
announcement.
Section
II. Award Information
1. Mechanism of Support
This Funding
Opportunity Announcement (FOA) will use the NIH Research Project Grant (R01) award mechanism.
The applicant will be solely responsible for planning, directing, and executing the proposed project.
This FOA uses “Just-in-Time” information concepts. It also uses the modular as well as the non-modular budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if you are a U.S. organization and are submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs), use the PHS398 Modular Budget component provided in the SF424 (R&R) Application Package and SF424 (R&R) Application Guide (see specifically Section 5.4, “Modular Budget Component,” of the Application Guide).
All foreign applicants must complete and submit budget requests using the Research & Related Budget component found in the application package for this FOA. See NOT-OD-06-096, August 23, 2006.
Competing renewal (formerly “competing continuation”) applications will not be accepted. At this time, it is not known if this FOA will be reissued.
2.
Funds Available
Because the nature and scope of the proposed research will vary from
application to application, it is anticipated that the size and duration of
each award will also vary. Although the financial plans of the Institutes and
Centers (ICs) provide support for this program, awards pursuant to this funding
opportunity are contingent upon the availability of funds and the submission of
a sufficient number of meritorious applications.
The NIAAA intends to commit approximately 1.5 million dollars in fiscal year 2007 to fund 3-4 applications. Applications submitted in response to this FOA will be capped at $250,000 in direct costs and use the modular budget mechanism.
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.
F&A
costs requested by consortium participants are not included in the direct cost
limitation. See NOT-OD-05-004,
November 2, 2004.
Section
III. Eligibility Information
1. Eligible Applicants
1.A. Eligible
Institutions
You may submit an
application(s) if your institution/organization has any of the following characteristics:
1.B. Eligible Individuals
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI 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.
More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a “team science” approach that clearly does not fit the single-PD/PI model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).
The decision of whether to apply for a single PD/PI or multiple PD/PI grant is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for multiple PD/PI grants will require additional information, as outlined in the instructions below. The NIH review criteria for approach, investigators, and environment have been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PD/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.
2.
Cost Sharing or Matching
This program does not require cost
sharing as defined in the current NIH
Grants Policy Statement.
3.
Other-Special Eligibility Criteria
Renewal
(formerly “competing continuation”) applications will not be accepted.
Applicants may submit more than one application, provided each application is scientifically distinct.
Section IV. Application and Submission Information
To download a SF424
(R&R) Application Package and SF424 (R&R) Application Guide for
completing the SF424 (R&R) forms for this FOA, link to http://www.grants.gov/applicants/apply_for_grants.jsp and follow the directions provided on that Web site.
A one-time registration is required for institutions/organizations at both:
PDs/PIs should work with their institutions/organizations to make sure they are registered in the eRA Commons.
Several additional separate actions are required before an applicant institution/organization can submit an electronic application, as follows:
1) Organizational/Institutional Registration in Grants.gov/Get Registered
2) Organizational/Institutional Registration in the eRA Commons
3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.
Both the PD/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.
Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.
Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.
1. Request Application Information
Applicants must
download the SF424 (R&R) application forms and the SF424 (R&R)
Application Guide for this FOA through Grants.gov/Apply.
Note:
Only the forms package directly attached to a specific FOA can be used. You
will not be able to use any other SF424 (R&R) forms (e.g., sample forms,
forms from another FOA), although some of the "Attachment" files may
be useable for more than one FOA.
For further assistance, contact GrantsInfo: Telephone
301-435-0714, Email: GrantsInfo@nih.gov.
Telecommunications for the hearing impaired: TTY
301-451-0088.
2. Content and Form of Application Submission
Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.
The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH (e.g., the “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”
The SF424 (R&R) application has several components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY includes all applicable components, required and optional. A completed application in response to this FOA includes the data in the following components:
Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Modular Budget or Research & Related Budget,
as appropriate (See Section IV.6., “Special Instructions,” regarding appropriate
required budget component.) Research
& Related Budget (required for foreign applications)
Optional Components:
PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form
Foreign
Organizations (Non-domestic (non-U.S.) Entity)
NIH policies concerning grants to
foreign (non-U.S.) organizations can be found in the NIH Grants Policy
Statement at: http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.
Applications from foreign organizations must:
Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.
SPECIAL INSTRUCTIONS
Applications with Multiple PDs/PIs
When multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the "Contact” PI, who will be responsible for all communication between the PDs/PIs and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above.
Information for the Contact PD/PI should be entered in item 15 of the SF424 (R&R) Cover component. All other PDs/PIs should be listed in the Research & Related Senior/Key Person component and assigned the project role of “PD/PI.” Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the “Credential” field of the Research & Related Senior/Key Person component. Failure to include this data field will cause the application to be rejected.
All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership of the project.
Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled “Multiple PD/PI Leadership Plan” (section 14 of the Research Plan Component in the SF424 (R&R) or Section I of the Research Plan in the PHS 398), must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, including communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.
If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.
Applications Involving a Single Institution
When all PDs/PIs are within a single institution, follow the instructions contained in the SF424 (R&R) Application Guide.
Applications Involving Multiple Institutions
When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget component. All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form. See Section 4.8 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form.
When submitting a modular budget, the prime institution completes the PHS398 Modular Budget component only. Information concerning the consortium/subcontract budget is provided in the budget justification. Separate budgets for each consortium/subcontract grantee are note required when using the Modular budget format. See Section 5.4 of the Application Guide for further instruction regarding the use of the PHS398 Modular Budget component.
3.
Submission Dates and Times
See Section IV.3.A. for details.
3.A.
Submission, Review, and Anticipated Start Dates
Opening Date: March 25,
2007 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt
Date: March 25, 2007
Application Receipt Date: April
25, 2007
Peer Review Date: July/August,
2007
Council Review Date: August,
2007
Earliest Anticipated Start Date: September
15, 2007
3.A.1. Letter of Intent
Prospective
applicants are asked to submit a letter of intent that includes the following
information:
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.
The letter of
intent is to be sent by the date listed in Section
IV.3.A.
The letter of
intent should be sent to:
Dr. Abraham P. Bautista
Chief, Extramural Project Review
Branch
Office of Extramural Activities
National Institute on Alcohol Abuse
and Alcoholism
National Institutes of Health
5635 Fishers Ln Room 3039
Rockville, MD 20852
Phone: 301 443 9737
Fax: 301 443 6077
Email: bautista@mail.nih.gov
3.B. Submitting an Application Electronically to the
NIH
To submit an application in response to this
FOA, applicants should access this FOA via http://www.grants.gov/applicants/apply_for_grants.jsp
and follow steps 1-4. Note: Applications must only be submitted
electronically. PAPER APPLICATIONS WILL NOT BE ACCEPTED.
In order to expedite the review, applicants are requested to notify the NIAAA Referral Office by email (bautista@mail.nih.gov) when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.
3.C.
Application Processing
Applications may be submitted on or after the opening date and must be
successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant
institution/organization) on the application submission/receipt date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the receipt
date(s) and time, the application may be delayed in the review process or not
reviewed.
Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two business days to view the application image.
Upon
receipt, applications will be evaluated for completeness by the CSR and responsiveness
by the NIAAA. Incomplete and non-responsive applications will not be reviewed.
If the
application is not responsive to the FOA, NIH staff may contact the applicant
to determine whether to return the application to the applicant or submit it
for review in competition with unsolicited applications at the next appropriate
NIH review cycle.
There will
be an acknowledgement of receipt of applications from Grants.gov and the Commons. The submitting AOR receives
the Grants.gov acknowledgments. The AOR and the PI receive Commons
acknowledgments. Information related to the assignment of an application to a
Scientific Review Group is also in the Commons.
Note: Since email can be unreliable, it is the responsibility of the applicant to check periodically on their application status in the Commons.
The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an “Introduction” describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.
4. Intergovernmental Review
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.
A grantee may, at its own risk and without NIH prior approval, incur
obligations and expenditures to cover costs up to 90 days before the beginning
date of the initial budget period of a new or competing renewal (formerly
“competing continuation”) award if such costs: are necessary to conduct the
project, and would be allowable under the grant, if awarded, without NIH prior
approval. If specific expenditures would otherwise require prior approval, the
grantee must obtain NIH approval before incurring the cost. NIH prior approval
is required for any costs to be incurred more than 90 days before the beginning
date of the initial budget period of a new or competing renewal award.
The incurrence of pre-award costs in anticipation of a competing or
non-competing award imposes no obligation on NIH either to make the award or to
increase the amount of the approved budget if an award is made for less than
the amount anticipated and is inadequate to cover the pre-award costs incurred.
NIH expects the grantee to be fully aware that pre-award costs result in
borrowing against future support and that such borrowing must not impair the
grantee's ability to accomplish the project objectives in the approved time
frame or in any way adversely affect the conduct of the project. See the NIH Grants
Policy Statement.
6. Other Submission
Requirements
PD/PI Credential (e.g., Agency Login)
The NIH requires the PD/PI(s) to fill in his/her Commons User ID in the “PROFILE – Project Director/Principal Investigator” section, “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component.
Organizational DUNS
The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”
PHS398 Research Plan Component Sections
Items 2-5 of the PHS398 Research Plan component are limited to 25 pages. While each section of the Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.
All application instructions outlined in the SF424 (R&R) Application Guide are to be followed, incorporating "Just-in-Time" information concepts, and with the following additional requirements:
Special Instructions for Modular Grant applications
R01 applications from U.S. institutions/organizations requesting up to $250,000 per year in direct costs (excluding consortium F&A costs) must be submitted in a modular budget format. Additional information on modular budgets is available at http://grants.nih.gov/grants/funding/modular/modular.htm. When submitting a modular budget, the applicant organization will include only the PHS398 Modular Budget component. See Section 5.4 of the SF424 (R&R) Application Guide for further instructions regarding the use of the PHS398 Modular Budget component.
Foreign organizations may not submit modular budgets. See NOT-OD-06-096.
Appendix Materials
IMPORTANT NOTE:
NIH has published new limitations on grant application appendix materials to
encourage applications to be as concise as possible while containing the
information needed for expert scientific review.
Applicants must follow the specific instructions on Appendix materials as described in the SF424 (R&R) Application Guide (See http://grants.nih.gov/grants/funding/424/index.htm).
Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.
Note: While each section of the PHS398 Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to monitor better formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.
Foreign Applications (Non-domestic (non-U.S.) Entity)
The
precise content of the data-sharing plan will vary, depending on the data being
collected and how the investigator is planning to share the data. Applicants
who are planning to share data may wish to describe briefly the expected
schedule for data sharing, the format of the final dataset, the documentation
to be provided, whether or not any analytic tools also will be provided,
whether or not a data-sharing agreement will be required and, if so, a brief
description of such an agreement (including the criteria for deciding who can
receive the data and whether or not any conditions will be placed on their
use), and the mode of data sharing (e.g., under their own auspices by mailing a
disk or posting data on their institutional or personal Web site, through a
data archive or enclave). Investigators choosing to share under their own
auspices may wish to enter into a data-sharing agreement. References to data
sharing may also be appropriate in other sections of the application.
All applicants must include a plan for sharing
research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing.
All investigators responding to this funding opportunity should include a
description of how final research data will be shared, or explain why data sharing
is not possible.
The reasonableness of the data sharing plan or the rationale for not sharing
research data will be assessed by the reviewers. However, reviewers will not
factor the proposed data sharing plan into the determination of scientific merit
or the priority score.
Sharing
Research Resources
NIH
policy expects that grant recipients make unique research resources readily
available for research purposes to qualified individuals within the scientific
community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131).
Investigators responding to this funding opportunity should include a sharing
research resources plan addressing how unique research resources will be shared
or explain why sharing is not possible.
The adequacy of the resources sharing plan and any
related data sharing plans will be considered by Program staff of the funding
organization when making recommendations about funding applications. The
effectiveness of the resource sharing will be evaluated as part of the
administrative review of each Non-Competing Grant
Progress Report (PHS 2590). See Section VI.3.,
“Reporting.”
Section V. Application Review Information
1. Criteria
Only the review criteria described below will be considered in the review process.
2. Review and Selection Process
Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIAAA in accordance with the review criteria stated below.
As part of the initial merit review, all applications will:
Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications. The following will be considered in making funding decisions:
The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application.
Note that an
application does not need to be strong in all categories to be judged likely to
have major scientific impact and thus deserve a high priority score. For
example, an investigator may propose to carry out important work that by its
nature is not innovative but is essential to move a field forward.
Significance: Does this study address an important problem? If
the aims of the application are achieved, how will scientific knowledge or
clinical practice be advanced? What will be the effect of these studies on the
concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field?
Approach: Are the
conceptual or clinical framework, design, methods, and analyses adequately
developed, well integrated, well reasoned, and appropriate to the aims of the
project? Does the applicant acknowledge potential problem areas and consider
alternative tactics?
For applications designating multiple PDs/PIs, is the leadership approach,
including the designated roles and responsibilities, governance, and
organizational structure, consistent with and justified by the aims of the
project and the expertise of each of the PDs/PIs?
Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?
Investigators: Are the PD/PI(s)
and other key personnel appropriately trained and well suited to carry out this
work? Is the work proposed appropriate to the experience level of the principal
investigator and other researchers? Does the PD/PI(s) and investigative team
bring complementary and integrated expertise to the project (if applicable)?
Environment: Do(es) the
scientific environment(s) in which the work will be done contribute to the
probability of success? Do the proposed studies benefit from unique features of
the scientific environment, or subject populations, or employ useful
collaborative arrangements? Is there evidence of institutional support?
2.A. Additional Review Criteria
In addition to the above
criteria, the following items will continue to be considered in the determination
of scientific merit and the priority score:
Care and Use of Vertebrate Animals in Research: If vertebrate animals
are to be used in the project, the adequacy of the plans for care and use of
vertebrate animals to be used in the project will be assessed. See the “Other
Research Plan Sections” of the PHS398 Research Plan component of the SF424
(R&R).
Biohazards: If materials or procedures are proposed that are potentially
hazardous to research personnel and/or the environment, determine if the proposed
protection is adequate.
2.B. Additional Review Considerations
Budget and Period of Support: The reasonableness of the proposed budget and the
appropriateness of the requested period of support in relation to the proposed
research may be assessed by the reviewers. The priority score should not be
affected by the evaluation of the budget.
Applications from Foreign Organizations: Whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources will be assessed.
2.C. Sharing Research Data
Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy.
2.D. Sharing Research Resources
NIH policy expects that grant recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.
Program staff will be responsible for the administrative review of the plan for sharing research resources.
The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590), See Section VI.3., “Reporting.”
3.
Anticipated Announcement and Award Dates
Not Applicable
Section
VI. Award Administration Information
1.
Award Notices
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 NIH eRA Commons.
If
the application is under consideration for funding, NIH will request
"just-in-time" information from the applicant. For details,
applicants may refer to the NIH
Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards,
Subpart A: General.
A formal notification in the form of a Notice of Award
(NoA) will be provided to the applicant organization. The NoA signed by the
grants management officer is the authorizing document. Once all administrative
and programmatic issues have been resolved, the NoA will be generated via email
notification from the awarding component to the grantee business official.
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. See Section
IV.5., “Funding Restrictions.”
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.
When multiple years are involved, awardees will be required to submit the Non-Competing Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.
1. Scientific/Research Contact(s):
Direct questions regarding neuroscience to
Lindsey Grandison, Ph.D
Division of
Neuroscience and Behavior
National Institute on Alcohol Abuse and Alcoholism
5635
Fishers Lane
Room
Number 2 057
Bethesda, MD 20892-9304
Telephone:
(301) 443 0606
Fax: 301 443 1650
Email; lgrandis@mail.nih.gov
Direct questions regarding measures of animal behavior to
Mark Egli, Ph.D
Division of
Neuroscience and Behavior
National Institute on Alcohol Abuse and Alcoholism
5635
Fishers Lane
Room
Number 2059
Bethesda,
MD 20892-9304
Telephone: (301) 594-6382
Fax: 301 443 1650
Email; megli@mail.nih.gov
2. Peer Review Contact(s):
Dr. Abraham P. Bautista
Chief,
Extramural Project Review Branch
Office of
Extramural Activities
National
Institute on Alcohol Abuse and Alcoholism
National
Institutes of Health
5635
Fishers Ln Room 3039
Rockville, MD 20852
Phone: 301.443.9737
Fax: 301
443 6077
Email: bautista@mail.nih.gov
3. Financial/Grants Management Contact(s):
Ms. Judy Fox
Chief, Grants Management Branch
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 3023, MSC 9304
Bethesda, MD 20892-9304
Phone: (301) 443-4704
FAX: (301) 443-3891
E-mail: jfox@mail.nih.gov
Section VIII. Other Information
Required Federal Citations
Use of Animals in
Research:
Recipients of PHS support for activities involving
live, vertebrate animals must comply with PHS Policy on Humane Care and Use of
Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf)
as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm),
and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm)
as applicable.
Sharing Research Data:
Investigators submitting an NIH application seeking
$500,000 or more in direct costs in any single year are expected to include a
plan for data sharing or state why sharing is not possible (http://grants.nih.gov/grants/policy/data_sharing).
Investigators should seek guidance from their
institutions, on issues related to institutional policies and local IRB rules,
as well as local, State and Federal laws and regulations, including the Privacy
Rule. Reviewers will consider the data sharing plan but will not factor the
plan into the determination of the scientific merit or the priority score.
Access
to Research Data through the Freedom of Information Act:
The Office of
Management and Budget (OMB) Circular A-110 has been revised to provide access
to research data through the Freedom of Information Act (FOIA) under some
circumstances. Data that are (1) first produced in a project that is supported
in whole or in part with Federal funds and (2) cited publicly and officially by
a Federal agency in support of an action that has the force and effect of law
(i.e., a regulation) may be accessed through FOIA. It is important for
applicants to understand the basic scope of this amendment. NIH has provided
guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this funding opportunity in a
public archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the application.
In addition, applicants should think about how to structure informed consent
statements and other human subjects procedures given the potential for wider
use of data collected under this award.
Sharing of
Model Organisms:
NIH is committed
to support efforts that encourage sharing of important research resources
including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm).
At the same time the NIH recognizes the rights of grantees and contractors to
elect and retain title to subject inventions developed with Federal funding
pursuant to the Bayh Dole Act (see the NIH
Grants Policy Statement. Beginning October 1, 2004, all investigators
submitting an NIH application or contract proposal are expected to include in
the application/proposal a description of a specific plan for sharing and
distributing unique model organism research resources generated using NIH
funding or state why such sharing is restricted or not possible. This will
permit other researchers to benefit from the resources developed with public
funding. The inclusion of a model organism sharing plan is not subject to a
cost threshold in any year and is expected to be included in all applications
where the development of model organisms is anticipated.
NIH Public Access Policy:
NIH-funded
investigators are requested to submit to the NIH manuscript submission (NIHMS) system
(http://www.nihms.nih.gov/) at PubMed
Central (PMC) an electronic version of the author's final manuscript upon acceptance
for publication, resulting from research supported in whole or in part with
direct costs from NIH. The author's final manuscript is defined as the final
version accepted for journal publication, and includes all modifications from
the publishing peer review process.
NIH is
requesting that authors submit manuscripts resulting from 1) currently funded
NIH research projects or 2) previously supported NIH research projects if they
are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms,
cooperative agreements, contracts, Institutional and Individual Ruth L.
Kirschstein National Research Service Awards, as well as NIH intramural
research studies. The Policy applies to peer-reviewed, original research
publications that have been supported in whole or in part with direct costs
from NIH, but it does not apply to book chapters, editorials, reviews, or
conference proceedings. Publications resulting from non-NIH-supported research
projects should not be submitted.
For more
information about the Policy or the submission process, please visit the NIH Public Access Policy Web site at http://publicaccess.nih.gov// and view the Policy or other Resources and Tools, including the Authors' Manual.
URLs in NIH Grant Applications or Appendices:
All
applications and proposals for NIH funding must be self-contained within
specified page limitations. For publications listed in the appendix and/or
Progress report, Internet addresses (URLs) or PubMed Central (PMC) submission
identification numbers must be used for publicly accessible on-line journal
articles. Publicly accessible on-line journal articles or PMC
articles/manuscripts accepted for publication that are directly relevant to the
project may be included only as URLs or PMC submission
identification numbers accompanying the full reference in either the
Bibliography & References Cited section, the Progress Report Publication
List section, or the Biographical Sketch section of the NIH grant application.
A URL or PMC submission identification number citation may be repeated in each
of these sections as appropriate. There is no limit to the number of URLs or
PMC submission identification numbers that can be cited.
Authority and Regulations:
This
program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the
intergovernmental review requirements of Executive Order 12372 or Health
Systems Agency review. 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. All awards are subject to the terms and conditions, cost
principles, and other considerations described in the NIH
Grants Policy Statement.
The PHS strongly
encourages all grant recipients to provide a smoke-free workplace and
discourage the use of all tobacco products. In addition, Public Law 103-227,
the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in
some cases, any portion of a facility) in which regular or routine education,
library, day care, health care, or early childhood development services are
provided to children. This is consistent with the PHS mission to protect and
advance the physical and mental health of the American people.
Loan Repayment
Programs:
NIH encourages
applications for educational loan repayment from qualified health professionals
who have made a commitment to pursue a research career involving clinical, pediatric,
contraception, infertility, and health disparities related areas. The LRP is an
important component of NIH's efforts to recruit and retain the next generation
of researchers by providing the means for developing a research career
unfettered by the burden of student loan debt. Note that an NIH grant is not
required for eligibility and concurrent career award and LRP applications are
encouraged. The periods of career award and LRP award may overlap providing the
LRP recipient with the required commitment of time and effort, as LRP awardees
must commit at least 50% of their time (at least 20 hours per week based on a
40 hour week) for two years to the research. For further information, please
see: http://www.lrp.nih.gov/.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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