Release Date:  November 22, 1999

RFA:  MH-00-002

National Institute of Mental Health 
National Institute of Neurological Disorders and Stroke
National Eye Institute
National Institute of Child Health and Human Development
National Institute on Aging
National Institute on Deafness and Other Communication Disorders
National Institute on Drug Abuse

Letter of Intent Receipt Date: February 28, 2000
Application Receipt Date: March 29, 2000



The purpose of this Request for Applications (RFA) is to solicit feasibility 
studies for profiling gene expression patterns in the mammalian nervous 
system.  Exploratory research projects supported under this RFA will utilize 
neural tissue-specific cDNA reagents and state-of-the-art microarray 
technologies, in order to quantify in a highly parallel way expression 
profiles of genes in mammalian neural tissue.  The creation of collaborative 
teams is encouraged, in which scientists with expertise in neuroscience 
research, genomics, and bioinformatics work to apply innovative approaches 
for analyzing microarray data.

Such feasibility studies will permit functional analyses of mouse and human 
neural tissue that aim to understand genes influencing the nervous system in 
their full biological context.  The widespread availability of innovative 
methods for gene expression profiling will stimulate many avenues of research 
on nervous system functioning and complex behavioral disorders.


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, Gene Expression 
Profiling in the Nervous System, is related to one or more priority areas.  
Applicants may obtain a copy of "Healthy People 2000" at


Applications may be submitted by foreign and domestic, 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 


This RFA will use the National Institutes of Health (NIH) Exploratory/ 
Developmental Grants (R21) mechanism.  Responsibility for the planning, 
direction, and execution of the proposed project will be solely that of the 
applicant. Because the purpose of R21 Exploratory/Developmental Grants is to 
support exploratory studies, establish feasibility of new approaches, and to 
help acquire preliminary data for use in preparing traditional R01 support, 
R21 grant applications received in response to this RFA are limited to two 
years with a maximum of $150,000 direct costs requested per year, and are not 
renewable. The anticipated award date is September 30, 2000.

For all competing R21 awards, specific application instructions have been 
modified to reflect “MODULAR GRANT” and “JUST-IN-TIME” streamlining efforts 
being undertaken at NIH.  More detailed information about modular grant 
applications, including a sample budget narrative justification pages and a 
sample biographical sketch, is available via the Internet at


This RFA is a one-time solicitation.  It is anticipated that about $3,750,000 
in total costs (including all direct and facilities and administrative costs) 
will be available for this initiative in Fiscal Year 2000, during which it is 
anticipated that 15 awards will be made.  The total project period for an 
application submitted in response to this RFA may not exceed two years.  
Awards pursuant to this RFA are contingent upon the availability of funds for 
this purpose.  The amount of funding for this initiative may be increased if 
a large number of highly meritorious applications are received and if funds 
are available.  Only applications that are found to be of the highest 
scientific merit will be considered for funding, and not all of the funding 
will be spent if there are not enough highly meritorious applications.  
Funding for the second year of the grant will be contingent upon satisfactory 
progress during the first year and availability of funds.

For the purpose of accomplishing the goals of this RFA, subcontracts may be 
included in the budget to support investigators at sites other than the 
awardee institution.  All direct and facilities and administrative 
subcontract costs in a given year will be counted toward the maximum of 
$150,000 direct costs requested by the awardee institution for that year.


Precise spatio-temporal expression of genes during development is critical 
for determining and maintaining the structure and function of the mammalian 
nervous system.  The determination of the profile of genes expressed in 
various brain cell types during development and aging, as well as alterations 
in gene expression patterns during pathophysiological states or in response 
to external influences, will provide valuable information that will 
contribute to a greater understanding of nervous system functioning.  This 
information may provide an experimental framework for new approaches and 
strategies that will lead to the improved diagnosis, treatment, and the 
eventual prevention of brain disorders.

In order to determine such expression patterns and decipher the molecular 
anatomy of the mammalian nervous system, NIH launched the Brain Molecular 
Anatomy Project (BMAP) as an interdisciplinary project to establish state-of-
the-art technologies and informatics systems.  This multi-institute effort 
consists of several distinct components.  The gene discovery component of 
BMAP is aimed at cataloguing the full repertoire of genes expressed in the 
nervous system, under both normal and abnormal conditions. 

The first funded BMAP gene discovery project supports construction of 
normalized, serially subtracted cDNA libraries from 10 brain regions of adult 
mouse brain, spinal cord, and retina (strain C57BL6J).  To date, a total of 
32,031 mouse brain 3’ EST sequences have been submitted to the dbEST database 
maintained by the National Center for Biotechnology Information (NCBI).  By 
the end of the two-year project period, approximately 100,000 5’ and 3’ mouse 
brain EST sequences will be generated and used to identify a non-redundant 
collection of >20,000 mouse brain UniGene cDNA sets.  The sequences of these 
mouse brain ESTs will be accessible through the NCBI-maintained dbEST 
database (, and all of the BMAP cDNA clones - 
including those representing members of unique mouse brain UniGene sets - 
will be made available to the scientific community through a distributor to 
be designated.

In addition to the BMAP mouse brain UniGene sets, other genomic resources 
have been generated in recent years.  For example, cDNA clones comprising 
UniGene sets for human and other mammals have been isolated, collected, and 
are available from many commercial distributors.

The availability of these genomic resources, along with DNA microarray 
technologies, presents a unique and unprecedented scientific opportunity for 
the neuroscience community to advance gene discovery and gene expression 
analysis.  DNA microarray technologies offer the ability to monitor 
simultaneously the expression patterns of large numbers of genes that are 
relevant to nearly every aspect of neuroscience research.  Nevertheless, 
there are many scientific issues and technical obstacles that need to be 
resolved before cDNA microarray technology can be used widely by individual 
neuroscientists for global analysis of gene expression patterns in the 
nervous system.

This RFA is intended to support research that will develop and apply 
experimental approaches and technologies to quantify, in a highly parallel 
way, expression profiles of genes in mammalian neural tissue.  These projects 
may utilize existing gene profiling resources, e.g., UniGene sets, array 
facilities, and analytic tools, currently available to the neuroscience 
community.  Applicants are encouraged to provide a plan to disseminate to the 
scientific community protocols, procedures, analytical tools, and other 
materials that may be developed in the course of the project.  Research 
topics of interest include, but are not limited to, the following:

o  Pilot projects to test the feasibility of determining global gene 
expression patterns of the nervous system, and to monitor changes in these 
patterns during development and under normal and experimental/pathological 

o  Projects to develop arrays containing restricted sets of cDNA clones and 
monitor alterations of gene expression in specific brain regions or cell 
types in the nervous system that occur in response to experimental 
manipulations such as administration of abused substances.

o  Projects to develop efficient experimental protocols for using cDNA arrays 
for studies of gene expression patterns in mammalian neural tissue.  Methods 
for preparation of microarray hybridization probes from a small amount of 
pathological specimen, embryonic tissue, micro-dissected tissue or single 
cell are of particular interest.

o  Projects to expand or enhance the capability of currently available image 
analysis and bioinformatics tools to measure and record data from 
microarrays.  The development and application of novel data tracking and 
management systems are of particular interest.

o  Projects to develop higher-order analysis bioinformatics tools and 
software algorithms to process microarray data for statistical analysis, 
cluster analysis, and mathematical modeling to characterize gene-gene 
interactions and functional pathways in the nervous system.


Prospective applicants are asked to submit, by February 28, 2000, a letter of 
intent that includes a descriptive title of the proposed research, the name, 
address, and telephone and facsimile numbers of the PI, the identities of 
other key personnel and participating institutions, and the number and title 
of this RFA.  Although a letter of intent is not required and is not binding, 
it is highly encouraged.  The information it contains will allow NIH program 
staff to estimate the workload and also to avoid potential conflicts of 
interest in the review.

Send the letter of intent to:

Dr. Hemin R. Chin
Division of Neuroscience & Basic Behavioral Science
National Institute of Mental Health
6001 Executive Boulevard, Room 7190, MSC 9643
Bethesda, MD 20892-9643
Telephone: (301) 443-1706
FAX: (301) 443-9890


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:  The application is also available at


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 


Modular Grant applications will request direct costs in $25,000 modules, up 
to a total direct cost request of $150,000 per year.  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 

PHS 398

FACE PAGE:  Items 7a and 8a should be completed to indicate Modular Direct 
Costs requested and Items 7b and 8b should reflect Total Costs (Modular 
Direct plus F&A costs).  Item 7 should reflect costs for the Initial Budget 
Period and item 8 should reflect costs for the Total Project Period.

of the PHS 398 (rev 4/98).  It is not required nor will it be accepted at the 
time of application.

categorical budget tables on page 5 of the PHS 398 (rev. 4/98) Form.  Only 
the requested total direct costs line for each year should be completed based 
on the number of $25,000 modules being requested.  Applicants may not request 
a change in the amount of each module.  A maximum of six modules (up to 
$150,000) may be requested for an R21 application.  Applicants may request up 
to two years of support for this RFA.  Direct cost budgets will remain 
constant throughout the life of the project (i.e., the same number of modules 
requested for all Project periods).  Any necessary escalation should be 
considered when determining the number of modules to be requested.  However, 
in the event that the number of modules requested must change in any future 
year due to the nature of the research proposed, appropriate justification 
must be provided.  Total Direct Costs for the Entire Proposed Project Period 
should be shown in the box provided.


o  Budget justifications should be provided under "Justifications" on Form 
Page 5 of the PHS 398.

o  List the names, role on the project and proposed percent effort for all 
project personnel (salaried or unsalaried)and provide a narrative 
justification for each person based on his/her role on the project.

o  Identify all consultants by name and organizational affiliation and 
describe the services to be performed.

o  Provide a general narrative justification for individual categories 
(equipment, supplies, etc.) required to complete the work proposed.  More 
detailed justifications should be provided for high cost items.  Any large 
one-time purchases, such as large equipment requests, must be accommodated 
within these limits.

CONSORTIUM/CONTRACTUAL COSTS:  If collaborations or subcontracts are involved 
that require transfer of funds from the grantee to other institutions, it is 
necessary to establish formal subcontract agreements with each collaborating 
institution.  A letter of intent from each collaborating institution should 
be submitted with the application.  Only the percentage of the 
consortium/contractual total costs (direct and facilities and administrative 
costs) relative to the total direct costs of the overall project needs to be 
stated at this time.  The following example should be used to indicate the 
percentage cost of the consortium, "The consortium agreement represents 27 
percent of overall direct costs requested in the first year."  A budget 
justification for the consortium should be provided as described in the 
"Budget Justification" section above (no Form Page 5 required for the 
consortium).  Please indicate whether the consortium will be in place for the 
entire project period and identify any future year changes in the percentage 
relative to the parent grant.

If there is a possibility of an award, the applicant will be requested to 
identify actual direct and facilities and administrative costs for all years 
of the consortium.  Please note that total subcontract costs need not be 
calculated in $25,000 modules.  However, when subcontract funds are added to 
the parent grant budget, the total direct cost amount must be included in the 
number of $25,000 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;
- List selected peer-reviewed publications, with full citations;
- Provide information, including overall goals and responsibilities, on 
research projects ongoing or completed during the last three years.

OTHER SUPPORT:  Do not complete the "Other Support" pages (Form Page 7).  
Selected other support information relevant to the proposed research may be 
included in the Biographical Sketch as indicated above.  Complete Other 
Support information will be requested by NIH staff if there is a possibility 
for an award.

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. It is important to identify all exclusions that were 
used 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.

Applications not conforming to these guidelines will be considered 
unresponsive to this RFA and will be returned without further review.

Any application subject to this policy that does not contain the required
information in a cover letter sent with the application will be returned to 
the applicant without 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 and must display 
the RFA number MH-00-001. A sample modified mailing label is available at  Please note this 
is in pdf format.  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 number and title, “MH-00-002: Gene 
Expression Profiling in the Nervous System,” must be typed on line 2 of the 
face page of the application form and the YES box must be marked. 

Submit a signed, typewritten original of the application, including the 
checklist and four signed single-sided photocopies, in one package to:

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

Submit one additional copy of the application, for receipt by the application 
receipt date of March 29, 2000, to:

Dr. Hemin R. Chin
Division of Neuroscience & Basic Behavioral Science
National Institute of Mental Health
6001 Executive Boulevard, Room 7190, MSC 9643
Bethesda, MD 20892-9643
Rockville, MD 20852 (for express/courier service)

Applications must be received by March 29, 2000.  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.  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.  The 
applicants should also ensure that their revised applications respond to the 
review criteria by which applications in response to this RFA will be 


Applications will be reviewed for scientific and technical merit by an 
appropriate peer review group convened by NIMH in accordance with the review 
criteria stated below.  As part of the initial merit review, all applications 
will receive a written critique and may undergo a process in which only those 
applications deemed to have the highest scientific merit, generally the top 
one half of applications under review, will be discussed, assigned a priority 
score, and receive a second level review by the appropriate 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.

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

o  Approach:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project?  Does the applicant develop multidisciplinary collaborations and 
acknowledge potential problem areas? Are alternative tactics considered?

o  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?

o  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?

o  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 

The initial review group will also examine: the appropriateness of proposed 
project budget and duration; the adequacy of plans to include both genders, 
minorities and their subgroups, and children as appropriate for the 
scientific goals of the research and plans for the recruitment and retention 
of subjects; the provisions for the protection of human and animal subjects; 
and the safety of the research environment.


The anticipated date of award is September 30, 2000. The following will be 
considered in making funding decisions:

o  Quality of the proposed project as determined by rigorous scientific peer 

o Promise of the proposed project to accomplish the goals of this RFA, by 
which global gene expression profiling of mammalian neural tissue will be 

o Program priorities and program balance.

o Availability of funds.


Letter of Intent Receipt Date:      February 28, 2000
Application Receipt Date:           March 29, 2000
Scientific Review Date:             June 2000
Advisory Council Date:              September 2000
Anticipated Award Date:             September 30, 2000


Written and telephone inquiries concerning this RFA are strongly encouraged.  
The opportunity to clarify any issues or questions from potential applicants 
is welcome.

Direct inquiries regarding programmatic issues to:

Dr. Hemin R. Chin
Division of Neuroscience and Basic Behavioral Science 
National Institute of Mental Health
6001 Executive Boulevard, Room 7190, MSC 9643
Bethesda, MD  20892-9643
Telephone:  (301) 443-1706
FAX:  (301) 443-9890

Dr. Robert Baughman
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard, Room 2137, MSC 9527
Bethesda, MD  20892-9527
Telephone:  (301) 496-1779
FAX:  (301) 402-1501 

Dr. Maria Y. Giovanni
Fundamental Retinal Processes
National Eye Institute
Executive Plaza South, Suite 350
6120 Executive Blvd. - MSC 7164
Bethesda, MD  20892-7164
Telephone: (301) 496-0484
FAX:  (301) 402-0528

Dr. Deborah Henken
Center for Research for Mothers and Children
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 4B01, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-5541
FAX:  (301) 480-0303

Dr. Bradley C. Wise
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging
Gateway Building, Suite 3C307
7201 Wisconsin Ave MSC9205
Bethesda, MD 20892-9205
Telephone: (301) 496-9350
Fax: (301) 496-1494

Dr. Rochelle Small
Division of Human Communication
National Institute on Deafness and Other Communication Disorders
6120 Executive Blvd. þ MSC 7180, Room 400C
Bethesda, MD 20892-7180
Telephone: (301) 402-3464
FAX: (301) 402-6251

Dr. Rebekah Rasooly
Division of Basic Research
National Institute on Drug Abuse
6001 Executive Boulevard, Room 4274, MSC 9555
Bethesda, MD 20892-9555
Telephone: (301) 435-1309
FAX: (301) 594-6043

Direct inquiries regarding fiscal matters to:

Ms. Diana S. Trunnell
Grants Management Branch
National Institute of Mental Health
6001 Executive Boulevard, Room 6115, MSC 9605
Bethesda, MD  20892-9605
Telephone: (301) 443-2805
FAX:  (301) 443-6885

Ms. Dawn Richardson
Grants Management Branch
National Institute of Neurological Disorders and Stroke 
6001 Executive Blvd., Room 3270, MSC 9190
Bethesda, MD  20892-9190
Telephone: (301) 496-7484
FAX: (301) 402-0219

Mr. William W. Darby
Grants Management Branch
National Eye Institute 
Executive Plaza South – MSC 7164, Suite 350
Bethesda, MD 20892-7164
Telephone: 301-496-5884
FAX: 301-496-9997 

Mr. E. Douglas Shawver
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-1303
FAX:  (301) 402-0915

Mr. Joseph Ellis
Grants Management Branch
National Institute on Aging
7201 Wisconsin Ave, Suite 2N212, MSC9205 
Bethesda, MD 20892-9205
Telephone: (301) 496-1472
Fax: (301) 402-3672

Ms. Sharon Hunt
Division of Extramural Research
National Institute on Deafness and Other Communication Disorders 
6120 Executive Boulevard, Room 400B - MSC 7180
Bethesda, MD  20892-7170
Telephone:  (301) 402-0909
FAX:  (301) 402-1757

Mr. Gary Fleming
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


This program is described in the Catalog of Federal Domestic Assistance Nos. 
93.242 (NIMH), 93.853(NINDS), 93.867 (NEI), 93.865 (NICHD), 93.866 (NIA), 
93.173 (NIDCD), and 93.279 (NIDA).  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 or 92.  
This program is not subject to the intergovernmental review requirements of 
Executive Order 12372 or Health Systems Agency review.  Awards will be 
administered under PHS policy as stated in the NIH Grants Policy Statement 
(October 1, 1998).

The PHS strongly encourages all grant and contract 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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