Release Date:  December 16, 1999

RFA:  DA-00-003

National Institute on Drug Abuse

Letter of Intent Receipt Date:  February 28, 2000
Application Receipt Date:       March 28, 2000



The National Institute on Drug Abuse (NIDA) announces the availability of 
funds for research project grants for the study of drug abuse and related 
areas using microarray technology.  NIDA supports over 85 percent of the 
world's research on the health aspects of drug abuse and addiction and serves 
as the foundation of the Nation's investment in understanding the causes, 
consequences, and treatment of drug addiction.  In an effort to expand our 
understanding of the basic biology of drug addiction, NIDA is initiating this 
grant program in order to support innovative studies that exploit the emerging 
microarray technology.  With this announcement, NIDA plans to develop a 
strong, multidisciplinary basic research program--drawing from neuroscience, 
genetics, behavioral science, bioengineering, and computational biology--aimed 
at adapting and applying microarray techniques to the general problem of drug 
abuse.  The creation of collaborative teams that will develop innovative 
approaches for analyzing microarray data is encouraged.  Eventually, it is 
anticipated that the identification of genes and gene products that may 
underlie the process of addiction will provide new targets for the development 
of new medications and therapies for drug abuse.


The Public Health Service (PHS) is committed to achieving the health promotion 
and disease prevention objectives of “Healthy People 2000,” a PHS-led national 
activity for setting priority areas.  This RFA, “Microarray-Based Research on 
Drug Abuse,” is related to one or more of the priority areas.  Potential 
applicants may obtain a copy of "Healthy People 2000" 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.  Awards to foreign institutions under R-series awards are 
generally limited to 5 years.


The mechanisms available for support of this program announcement include 
project grant (R01) and exploratory/developmental grant (R21).  Applicants are 
advised to contact NIDA program staff listed under INQUIRIES for additional 
information and specific application procedures. 

For research in methods development, the R21 mechanism is particularly 
appropriate. The exploratory/developmental (R21) grants are non-renewable and 
limited to $100,000 direct cost amount per year.  The R21 mechanism is 
intended to encourage exploratory research projects with sound methodology and 
strong rationales in underdeveloped research areas of drug abuse, such as the 
areas covered in this RFA.  Investigators may also choose to include methods 
development as one component within the R01 mechanism.  Specific information 
on individual research mechanisms can be obtained from the NIDA home page at 

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.  This 
RFA is a one-time solicitation.


NIDA intends to commit approximately $2,000,000 in FY 2000 to fund 
approximately five-six new grants in response to this RFA. An applicant may 
request a project period of up to 3 years.  Because the nature and scope of 
the research proposed may vary, it is anticipated that the size of each award 
will also vary. Although the financial plans of NIDA 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 applications of outstanding 
scientific and technical merit.



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 

It has been shown that administration and/or withdrawal of opiates and other 
drugs of abuse induce the expression of specific genes and their protein 
products.  In some cases, experimental overexpression or knock-out of these 
genes mimics or blocks the effects of the drugs, suggesting that gene 
expression plays a crucial role in mediating the response to drugs.  
Therefore, it is of interest to use microarrays to determine how abused drugs 
affect 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, VTA, amygdala and prefrontal cortex, are important sites in the 
response to addictive drugs.  The nature of the relevant 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 the same substance, and within any region, only a 
particular subset of neurons may play a critical role in the biology of 
addiction.  Consequently, it is of paramount importance to clearly define the 
regions of the brain to be analyzed so that the signal-to-noise ratio is high.

Ultimately, analysis of post-mortem human or mammalian tissue with microarrays 
may provide a “fingerprint” of gene and/or protein expression in particular 
cell types that characterizes the addicted brain.  It is anticipated that 
basic research findings in this area will rapidly feed into NIDA’s applied 
medications development efforts; the identification of additional genes or 
gene products that potentially underlie the process of addiction will provide 
new targets both for traditional drug discovery efforts and for the potential 
development of gene therapies.
In addition, microarrays are a powerful tool that may be relevant to other 
areas of drug abuse research, such as behavioral genetics.  It is often 
difficult to isolate quantitative trait loci (QTLs) and specific loci 
implicated in mediating complex behaviors because they map to large areas of 
the chromosome containing many genes.  In some studies, microarrays have been 
used to compare the expression of all the genes in a target region in control 
and affected individuals, thus identifying specific candidate genes for 
further study.

In the future, microarray technology may become even more useful and powerful 
as new data analysis tools and novel applications, such as protein expression 
microarrays, are developed.

Areas of Interest

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

o  Characterization of an overall expression pattern of neural tissues or 
cells in response to addictive drugs. 

o  Profiling the expression of enzymes involved in metabolism of addictive 

o  Developmental profiling of gene expression in brain regions that mediate 
addictive behavior.

o  Identification of unique patterns of gene expression associated with 
addiction, the response to environmental cues that promote relapse, or other 
drug abuse behaviors.

o  Innovative uses of microarrays in studies of the genetics of behavior 
and/or drug abuse.


Data Sharing Plan: Dissemination of Data and Biological Materials

The sharing of biological materials, data, and research tools in a timely 
manner has been an essential element in the rapid progress that has been made 
in the analysis of complex traits such as substance abuse.  PHS policy is that 
investigators make unique research resources readily available for research 
purposes to qualified individuals within the scientific community when first 
results based on these resources have been published (PHS Grants Policy 
Statement in the July 12, 1996, issue of the NIH Guide to Grants and 
Contracts).  Accordingly, NIDA expects applicants who respond to this RFA to 
develop and propose detailed plans for sharing the data and materials 
generated through the grant.  It is expected that the information to be 
distributed will include all novel research tools and clone sets, as well as 
the data generated from the arrays.

It is expected that the Data Sharing Plan will specify the following elements:  
1) the creation of comprehensive databases that contain the microarray 
analysis results collected and produced by the grant, 2) a mechanism or 
protocol by which the databases can be widely searched and/or distributed to 
qualified investigators in the scientific community, 3) a mechanism by which 
biological materials (e.g., DNA samples, arrays) and research tools can be 
distributed to qualified investigators in the scientific community, and 4) a 
timetable specifying when the database and/or biological materials and/or 
research tools will be available for distribution.

The Scientific Review Group will be asked to comment on the proposed plan for 
data sharing and access, and the adequacy of the plan will be considered by 
NIDA in making funding decisions.  The plan must be approved by NIDA (after 
negotiation with the applicant if necessary) before an award will be made. 


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: 


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.


The National Advisory Council on Drug Abuse recognizes the importance of 
research involving the administration of drugs to human subjects and has 
developed guidelines relevant to such research.  Potential applicants are 
encouraged to obtain and review these recommendations before submitting an 
application that will administer compounds to human subjects.  The guidelines 
are available on NIDA's Home Page at http://www.nida.nih.gov under "What's 
New" or may be obtained by calling (301) 443-2755.


Prospective applicants are asked to submit a letter of intent by February 28, 
2000, 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 is 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 
NIDA staff to estimate the potential review workload and plan review of the 

The letter of intent is to be sent to:

Director, Office of Extramural Program Review
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3158, MSC 9547
Bethesda, MD  20892-9547
Telephone:  (301) 443-2755
FAX:  (301) 443-0538


The research grant application form PHS 398 (rev. 4/98) is to be used in 
applying for these grants.  Application kits are available at most 
institutional offices of sponsored research and may be obtained 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, E-mail:  GrantsInfo@nih.gov.  


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.


Modular Grant applications will request direct costs in $25,000 modules, up to 
a total direct cost request of $250,000 per year.  (Applications that request 
more than $250,000 direct costs in any year must follow the traditional PHS 
398 application instructions.)  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 up to a maximum of $250,000) 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.

the PHS 398.  It is not required and will not be accepted with the 

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 role in 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:  

- 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 title 
and number of this RFA must be typed in Item 2 on the face page of the 
application form, and the YES box must be marked.  The RFA number must be 
typed on the label as well.

The sample RFA label is 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 the 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:

Director, Office of Extramural Program Review
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3158, MSC 9547
Bethesda, MD  20892-9547
Rockville, MD  20852 (for express/courier service)

Applications must be received by March 28, 2000.  If an application is 
received after that date, it will be returned to the applicant without review.  
The Center for Scientific Research (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 
for responsiveness by NIDA.  Incomplete and/or non-responsive applications 
will be returned to the applicant without further consideration.

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 
NIDA in accordance with the review criteria stated below.  As part of the 
initial merit review, a process will be used by the initial review group in 
which applications 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 NIDA National 
Advisory Council or Board.

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 

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 

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:    February 28, 2000
Application Receipt Date:         March 28, 2000
Peer Review Date:                 Summer 2000
Council Review:                   September 2000
Earliest Anticipated Start Date:  September 29, 2000


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 welcome.

Direct inquiries regarding programmatic issues to:

Rebekah S. Rasooly, Ph.D.
Division of Neurosciences & Behavioral Research
National Institute on Drug Abuse
6001 Executive Boulevard, Room 4282, MSC 9555
Bethesda, MD  20892
Telephone:  (301) 443-6300
FAX:  (301) 594-6043
Email:  rr185i@nih.gov

Direct inquiries regarding review matters to:

Teresa Levitin, Ph.D.
Director, Office of Extramural Program Review
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3158, MSC 9547
Bethesda, MD  20892-9547
Telephone :  (301) 443-2755
FAX:  (301) 443-0538
E-mail:  tl25u@nih.gov

Direct inquiries regarding fiscal matters to:

Gary Fleming, J.D., M.A.
Grants Management Branch
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3131, MSC 9541
Bethesda, MD  20892-9541
Telephone:  (301) 443-6710
FAX:  (301) 594-6847
Email:  gf6s@nih.gov


This program is described in the Catalog of Federal Domestic Assistance No.
93.279.  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 PHS 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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