Release Date:  April 6, 2000

RFA:  AA-00-004

National Institute on Alcohol Abuse and Alcoholism

Letter of Intent Receipt Date:  June 19, 2000
Application Receipt Date:       July 18, 2000



The National Institute on Alcohol Abuse and Alcoholism (NIAAA) 
announces the availability of funds for research project grants for the 
study of ethanol’s effects on behavior, nervous system function, and 
organ pathophysiology using emerging microarray technology.  NIAAA also 
encourages the formation of multidisciplinary teams of investigators--
drawing from neuroscience, genetics, molecular biology, biochemistry, 
behavioral science, bioengineering, and computational biology--for this 
purpose.  NIAAA anticipates that such studies will aid in the 
identification of genes and gene products mediating neurobiological and 
behavioral changes and tissue damage induced by acute and chronic 
exposure to ethanol, thereby providing new targets for the development 
of medications for prevention and treatment of alcoholism and the 
biomedical consequences of alcohol abuse.


The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of "Healthy People 2010," a 
PHS-led national activity for setting priority areas. This Request for 
Applications (RFA), Microarray-Based Research on Alcohol’s Effects on 
Behavior, Nervous System Function, and Organ Pathophysiology, is 
related to one or more of the priority areas. Potential applicants may 
obtain a copy of "Healthy People 2010" at 


Applications may be submitted by domestic and foreign, for-profit and 
non-profit organizations, public and private, such as universities, 
colleges, hospitals, laboratories, units of State and local 
governments, and eligible agencies of the Federal government. 
Racial/ethnic minority individuals, women, and persons with 
disabilities are encouraged to apply as Principal Investigators.

This RFA will use the National Institutes of Health (NIH) research 
project grant (R01) and the NIAAA exploratory/developmental grant (R21) 
award mechanisms. Responsibility for the planning, direction, and 
execution of the proposed project will be solely that of the applicant. 
The total project period for an application submitted in response to 
this RFA may not exceed 3 years.  Applications for competitive 
supplements to funded NIAAA grants will also be considered responsive 
to this RFA.  Competitive supplement applications are limited in 
duration to the funding period of the parent grant.  This RFA is a one-
time solicitation.  Future unsolicited competing continuation 
applications will compete with all investigator-initiated applications 
and be reviewed according to the customary peer review procedures. The 
earliest anticipated award date is December, 2000 under expedited 
Council review procedures.

Applicants may also submit applications for Investigator-Initiated 
Interactive Research Project Grants (IRPG). Interactive Research 
Project Grants require the coordinated submission of related research 
project grants (R01) from investigators who wish to collaborate on 
research, but do not require extensive shared physical resources. These 
applications must share a common theme and describe the objectives and 
scientific importance of the interchange of, for example, ideas, data, 
and materials among the collaborating investigators. A minimum of two 
independent investigators with related research objectives may submit 
concurrent, collaborative, cross- referenced individual R01 
applications. Applicants may be from one or several institutions. 
Further information on these and other grant mechanisms may be obtained 
from the program staff listed in the INQUIRIES section of this RFA or 
from the NIAAA Web site http://www.niaaa.nih.gov/ under Research 
Programs/Program Announcements.

The NIAAA intends to commit approximately $2 million in FY 2001 to fund 
six to eight new and/or competitive continuation grants in response to 
this RFA.  An applicant may request a project period of up to 3 years 
with direct costs not to exceed $300,000 per year.  Waivers for 
exceptional circumstances to exceed this limit should contact Program 
Staff as indicated under “Inquiries” below.  Under the R21 mechanism, 
direct costs are limited to $100,000 per year. (See Program 
Announcement PA-99-131, “NIAAA Exploratory/Developmental Grant 
Program,” https://grants.nih.gov/grants/guide/pa-files/PA-99-131.html, 
for a complete description of the R21 mechanism.)  Because the nature 
and scope of the research proposed might vary, it is anticipated that 
the size of awards will also vary. Although the financial plans of the 
NIAAA provide support for this program, awards pursuant to this RFA are 
contingent upon the availability of funds and the receipt of a 
sufficient number of meritorious applications.  At this time, it is not 
known if this RFA will be reissued. 



Microarrays represent a powerful new technology that has been applied 
to a variety of research questions.  For example, oligonucleotide/cDNA 
arrays have been used to analyze the overall expression patterns of 
cells and tissues under various conditions, to identify amplified 
regions of the genome, and to search for specific changes in gene 
expression caused by variants or mutant alleles.  

It has been shown that administration and/or withdrawal of ethanol 
induces the expression of specific genes and their protein products.  
The precise changes in gene expression depend on the dose and duration 
of ethanol exposure, and the tissue preparation under study.  It seems 
likely that some of these changes in gene expression play a crucial 
role in mediating physiological and behavioral responses to ethanol.  
Therefore, it is of interest to use microarrays to determine how 
ethanol affects the overall gene expression pattern, and ultimately the 
overall protein expression pattern, in specific target cells.  

Research has shown that particular regions of the brain, such as the 
nucleus accumbens, ventral tegmental area, amygdala and prefrontal 
cortex are important sites in the response to ethanol.  The critical 
changes in gene expression in these and other target brain regions may 
be relatively small quantitatively.  Furthermore, different brain 
regions may respond in alternate or even opposite ways to ethanol, and 
within any region, only a particular subset of neurons may play a 
critical role in responses to ethanol.  It is therefore of paramount 
importance to define the regions of the brain to be analyzed as 
precisely as possible, so that the signal-to-noise ratio is high.  

Ultimately, analysis of post-mortem human or mammalian tissue with 
microarrays may provide a comprehensive profile of gene and/or protein 
expression in particular cell types, which collectively characterizes 
the physiological states of neurons associated with behavioral 
phenomena such as tolerance, dependence, and withdrawal.  This approach 
can also highlight differences in gene expression between individuals 
(or strains of animal) with high vs. low responses to ethanol (e.g., 
sedation, ataxia, withdrawal, locomotor activation). 

Ethanol is a potent teratogen that causes a spectrum of brain damage, 
including fetal alcohol syndrome.  Depending on dose of ethanol and 
timing of exposure, specific brain regions and cell populations are 
differentially affected.  Analysis of tissues with microarrays could 
provide insights about the relationship between functional alterations 
during development and subsequent neurological and behavioral deficits.  
Responses in plasticity to specific prenatal and postnatal 
manipulations can also be evaluated.  

The initiation and progression of ethanol-induced organ pathogenesis is 
a complex process that involves the induction of genes and their 
protein products at multiple sites.  Elucidating the specific molecular 
targets of ethanol’s actions in specific organs will facilitate the 
development of appropriate drug interventions.  As with brain, it will 
be important to delineate specific cell populations for evaluation with 

The technology and analytic methodology for micorarray-based studies 
are now at a relatively early stage of development.  NIAAA encourages 
studies using current technology, as well as those which incorporate 
development and improvement of microarray-based methods.

Areas of Interest

Current areas of research that are considered relevant include but are 
not limited to:  

o  Characterization of overall gene expression pattern of neural 
tissues or cells in response to acute or chronic exposure to ethanol.  

o  Identification of unique patterns of gene expression due to prenatal 
and/or neonatal exposure to ethanol.

o  Identification of unique patterns of gene expression describing 
organ system pathology due to ethanol exposure, e.g., cardiomyopathy, 
pancreatitis, alcoholic liver disease.

o  Identification of unique patterns of gene expression associated with 
specific behavioral responses to ethanol.

o  Comparison of gene expression patterns in strains of animals 
differing in specific responses to ethanol (e.g., consumption, 
sedation, and withdrawal).



Projects funded under this RFA are likely to lead to the creation of 
new gene arrays, gene expression data, analytic methods for gene 
expression patterns, and other research tools which will be of great 
value to the broader research community, beyond the laboratories which 
will create them.  NIAAA strongly encourages the maximal dissemination 
of these tools to the broader research community to ensure that they 
may be exploited to their full potential.  NIAAA accordingly requires 
applicants who respond to this RFA to propose detailed plans for 
sharing the research resources that will be generated through the 

It is expected that the investigator’s resource sharing plan will 
include a description of the mechanisms proposed for wide distribution 
of resources with investigators in the scientific community, and a 
timetable for distribution of resources.  The reviewers will make an 
administrative comment on the adequacy of the proposed plan for 
resource sharing.  (This comment will not affect the priority score of 
the proposal.)  NIAAA program staff will consider the adequacy of the 
plan in determining whether to recommend an application for award.  The 
sharing plan as approved, after negotiation with the applicant as 
necessary, shall become a condition of the grant award.  Where 
appropriate, grantees may work with the private sector to make 
resources available to the wider research community at a reasonable 
cost.  Applicants may request funds to defray the costs of sharing 
resources, with adequate justification.  For more detailed guidance on 
NIH’s policies on resource sharing, applicants are referred to 
“Principles and Guidelines for Recipients of NIH Research Grants and 
Contracts on Obtaining and Disseminating Biomedical Research 
Resources,” http://www.ott.nih.gov/policy/rt_guide_final.html.

It is the policy of the NIH that women and members of minority groups 
and their subpopulations must be included in all NIH supported 
biomedical and behavioral research projects involving human subjects, 
unless a clear and compelling rationale and 
justification is provided that inclusion is inappropriate with respect 
to the health of the subjects or the purpose of the research.  This 
policy results from the NIH Revitalization Act of 1993 (Section 492B of 
Public Law 103-43).  

All investigators proposing research involving human subjects should 
read the "NIH Guidelines for Inclusion of Women and Minorities as 
Subjects in Clinical Research," which was published in the Federal 
Register of March 28, 1994 (FR 59 14508-14513) and in the NIH Guide for 
Grants and Contracts, Vol. 23, No. 11, March 18, 1994, available on the 
Web at https://grants.nih.gov/grants/guide/notice-files/not94-100.html.  


It is the policy of NIH that children (i.e., individuals under the age 
of 21) must be included in all human subjects’ research, conducted or 
supported by the NIH, unless there are scientific and ethical reasons 
not to include them. This policy applies to all initial (Type 1) 
applications submitted for receipt dates after October 1, 1998.  

All investigators proposing research involving human subjects should 
read the "NIH Policy and Guidelines" on the Inclusion of Children as 
Participants in Research Involving Human Subjects that was published in 
the NIH Guide for Grants and Contracts, March 6, 1998, and is available 
at the following URL address: 
https://grants.nih.gov/grants/guide/notice-files/not98-024.html . 

Investigators also may obtain copies of these policies from the program 
staff listed under INQUIRIES. Program staff may also provide additional 
relevant information concerning the policy.


All applications and proposals for NIH funding must be self-contained 
within specified page limitations. Unless otherwise specified in a NIH 
solicitation, internet addresses (URLs) should not be used to provide 
information necessary to the review because reviewers are under no 
obligation to view the Internet sites. Reviewers are cautioned that 
their anonymity may be compromised when they directly access an 
Internet site.


Prospective applicants are asked to submit a letter of intent that 
includes a descriptive title of the proposed research, the name, 
address, and telephone number of the Principal Investigator, the 
identities of other key personnel and participating institutions, and 
the number and title of the RFA in response to which the application 
may be submitted. 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 Institute staff to 
estimate the potential review workload and avoid conflict of interest 
in the review.

The letter of intent is to be sent to 

Extramural Project Review Branch, 
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 409, MSC 7003 
Bethesda, MD 20892-7003
by the letter of intent receipt date listed in the heading of this RFA.


The research grant application form PHS 398 (rev. 4/98) is to be used 
in applying for these grants. These forms are available at most 
institutional offices of sponsored research and from the Division of 
Extramural Outreach and Information Resources, National Institutes of 
Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, 
telephone 301/710-0267, email: GrantsInfo@nih.gov.  Applications are 
also available at:  https://grants.nih.gov/grants/forms.htm.


The modular grant concept establishes specific modules in which direct 
costs may be requested, as well as a maximum level for requested 
budgets. Only limited budgetary information is required under this 
approach. The just-in-time concept allows applicants to submit certain 
information only when there is a possibility for an award. It is 
anticipated that these changes will reduce the administrative burden 
for the applicants, reviewers, and Institute staff. The research grant 
application form PHS 398 (rev. 4/98) is to be used in applying for 
these grants, with the modifications noted below.


All applications will use the Modular Grant  format and request direct 
costs in $25,000 modules.  The total direct costs must be requested in 
accordance with the program guidelines and the modifications made to 
the standard PHS 398 application instructions described below:

PHS 398 FACE PAGE - Items 7a and 7b should be completed, indicating 
Direct Costs (in $25,000 increments  and Total Costs [Modular Total 
Direct plus Facilities and Administrative (F&A) costs] for the initial 
budget period. Items 8a and 8b should be completed indicating the 
Direct and Total Costs for the entire proposed period of support. 

Page 4 of the PHS 398. It is not required and will not be accepted with 
the application. 

categorical budget table on Form Page 5 of the PHS 398. It is not 
required and will not be accepted with the application.

NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant Budget 
Narrative page. (See 
https://grants.nih.gov/grants/funding/modular/modular.htm, for sample 
pages.) At the top of the page, enter the total Direct Costs requested 
for each year. This is not a Form page. Under Personnel, list key 
project personnel, including their names, percent of effort, and roles 
on the project. No individual salary information should be provided. 
However, the applicant should use the NIH appropriation language salary 
cap and the NIH policy for graduate student compensation in developing 
the budget request.  For Consortium/Contractual costs, provide an 
estimate of total costs (Direct plus F&A) for each year, each rounded 
to the nearest $1,000. List the individuals/organizations with whom 
consortium or contractual arrangements have been made, the percent 
effort of key personnel, and the role on the project. Indicate whether 
the collaborating institution is foreign or domestic. The total cost 
for a consortium/contractual arrangement is included in the overall 
requested Modular Direct Cost amount. Include the letter of intent to 
establish a consortium.  Provide an additional narrative budget 
justification for any variation in the number of modules requested.

BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used 
by reviewers in the assessment of each individual"s qualifications for 
a specific role in the proposed project, as well as to evaluate the 
overall qualifications of the research team. A biographical sketch is 
required for all key personnel, following the instructions below. No 
more than three pages may be used for each person. A sample 
biographical sketch may be viewed at: 
https://grants.nih.gov/grants/funding/modular/modular.htm. - Complete 
the educational block at the top of the Form page, - List position(s) 
and any honors, - Provide information, including overall goals and 
responsibilities, on research projects ongoing or completed during the 
last three years, and- List selected peer-reviewed publications, with 
full citations. 

CHECKLIST - This page should be completed and submitted with the 
application. If the F&A rate agreement has been established, indicate 
the type of agreement and the date. All appropriate exclusions must be 
applied in the calculation of the F&A costs for the initial budget 
period and all future budget years.  The applicant should provide the 
name and phone number of the individual to contact concerning fiscal 
and administrative issues if additional information is necessary 
following the initial review. 

The RFA label available in the PHS 398 (rev. 4/98) application form 
must be affixed to the bottom of the face page of the application. 
Failure to use this label could result in delayed processing of the 
application such that it may not reach the review committee in time for 
review. In addition, the RFA title and number must be typed on line 2 
of the face page of the application form and the YES box must be 

The sample RFA label available at:
 https://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been 
modified to allow for this change. Please note this is in pdf format. 

Submit a signed, typewritten original of the application, including the 
Checklist, and three signed photocopies in one package to:

6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710 
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)

At the time of submission, two additional copies of the application 
must be sent to:

RFA :AA-00-004
Extramural Project Review Branch
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 409, MSC 7003
Bethesda, MD 20892-7003
Rockville, MD 20852 (for express/courier service)

Applications must be received by the application receipt date listed in 
the heading of this RFA. If an application is received after that date, 
it will be returned to the applicant without review. 

The Center for Scientific Review (CSR) will not accept any application 
in response to this RFA that is essentially the same as one currently 
pending initial review, unless the applicant withdraws the pending 
application. The CSR will not accept any application that is 
essentially the same as one already reviewed. This does not preclude 
the submission of substantial revisions of applications already 
reviewed, but such applications must include an introduction addressing 
the previous critique.


Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by the NIAAA.  Incomplete applications will be 
returned to the applicant without further consideration.  If the 
application is not responsive to the RFA, CSR 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 review cycle.

Applications that are complete and responsive to the RFA will be 
evaluated for scientific and technical merit by an appropriate peer 
review group convened by the NIAAA in accordance with the review 
criteria stated below. As part of the initial merit review, all 
applications will receive a written critique and undergo a process in 
which only those applications deemed to have the highest scientific 
merit, generally the top half of the applications under review, will be 
discussed, assigned a priority score, and receive a second level review 
by the NIAAA National Advisory Council.

Review Criteria

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health. 
In the written comments reviewers will be asked to discuss the 
following aspects of the application 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 the 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.  

(1) Significance:  Does this study address an important problem? If the 
aims of the application are achieved, how will scientific knowledge be 
advanced? What will be the effect of these studies on the concepts or 
methods that drive this field?  

(2) Approach:  Are the conceptual framework, design, methods, and 
analyses adequately developed, well-integrated, and appropriate to the 
aims of the project?  Does the applicant acknowledge potential problem 
areas and consider alternative 
tactics?  (For the R21 mechanism, a strong rationale and conceptual 
framework are normally sufficient for establishing the feasibility of 
the project, in lieu of extensive preliminary data.)  

(3) Innovation:  Does the project employ novel concepts, approaches, or 
methods? Are the aims original and innovative?  Does the project 
challenge existing paradigms or develop new methodologies or 
technologies?  Does the applicant propose novel 
approaches to improve the accuracy, efficiency, and usefulness of 
microarray-based assays?  

(4) Investigator:  Is the investigator 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, 
if any?  

(5) Environment:  Does the scientific environment in which the work 
will be done contribute to the probability of success?  Do the proposed 
experiments take advantage of unique features of the scientific 
environment or employ useful collaborative arrangements?  Is there 
evidence of institutional support?  

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:  

o  The adequacy of plans to include both genders, minorities and their 
subgroups, and children as appropriate for the scientific goals of the 
research.  Plans for the recruitment and retention of subjects will 
also be evaluated.  

o  The reasonableness of the proposed budget and duration in relation 
to the proposed research  

o  The adequacy of the proposed protection for humans, animals, or the 
environment, to the extent they may be adversely affected by the 
project proposed in the application.  

The review group will also comment on plans for data sharing.

Letter of Intent Receipt Date:    June 19, 2000
Application Receipt Date:         July 18, 2000
Peer Review Date:                 October 2000

Earliest Anticipated Start Date:  December, 2000 under expedited 
Council review procedures. 


Award criteria that will be used to make award decisions include:

o  scientific merit (as determined by peer review)
o  availability of funds
o  programmatic priorities
o  adequacy of plans for data sharing


Inquiries concerning this RFA are encouraged.  The opportunity to 
clarify any issues or questions from potential applicants is 

Direct inquiries regarding programmatic issues on neuroscience and 
behavior to:

Robert W. Karp, Ph.D.
Division of Basic Research
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 402, MSC 7003
Bethesda, MD  20892-7003
Telephone:  (301) 443-2239
FAX:  (301) 594-0673
Email: rkarp@willco.niaaa.nih.gov

Direct inquiries regarding programmatic issues on prenatal ethanol 
exposure and ethanol-induced organ pathology to:

Laurie Foudin, Ph.D.
Division of Basic Research
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 402, MSC 7003
Bethesda, MD  20892-7003
Telephone:  (301) 443-0912
FAX:  (301) 594-0673
Email:  lfoudin@willco.niaaa.nih.gov

Direct inquiries regarding fiscal matters to:

Judy Simons
Grants Management Branch
Office of Planning and Resource Management
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 504, MSC 7003
Bethesda, MD 20892-7003
Telephone:  (301) 443-2434
FAX:  (301) 443-3891
Email:  jsimons@willco.niaaa.nih.gov


This program is described in the Catalog of Federal Domestic Assistance 
No. 93.273. Awards are made under authorization of the Public Health 
Service Act, Title IV, Part A (Public Law 78-410, as amended by Public 
Law 99-158, 42 USC 241 and 285) and administered under NIH grants 
policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This 
program is not subject to the intergovernmental review requirements of 
Executive Order 12372 or Health Systems Agency review.

The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and promote the non-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.

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