SILVIO O. CONTE CENTERS FOR NEUROSCIENCE RESEARCH

Release Date:  April 17, 1998

PA NUMBER:  PAR-98-057

P.T.

National Institute of Mental Health

Letter of Intent Receipt Date:  July 1
Application Receipt Date:  October 20

PURPOSE

The National Institute of Mental Health (NIMH) invites research grant
applications for Silvio O. Conte Centers for Neuroscience Research (CCNR).  The
purpose of this program is to provide a unifying framework for the pursuit of
basic neuroscience research relevant to mental health and mental illness.  A CCNR
should conduct novel, integrative, and hypothesis driven research on a highly
focused and well defined overarching neuroscience question which is relevant to
the mission of NIMH.  It is expected that these centers will encourage
investigators representing a variety of disciplines and/or approaches to bring
to the field of mental health research the full range of expertise and advanced
technologies available in the basic sciences.

HEALTHY PEOPLE 2000

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 PA, Silvio O. Conte Centers for
Neuroscience Research, is related to the priority area of mental health and
mental disorders.  Potential applicants may obtain a copy of "Healthy People
2000" (Full Report:  Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-
001-00473-1) through the Superintendent of Documents, Government Printing Office,
Washington, DC 20402-9325 (telephone 202-512-1800).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by 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.  Foreign institutions are not eligible for Center Grants
(P50). Racial/ethnic minority individuals, women, and persons with disabilities
are encouraged to apply as CCNR Directors and heads of projects.

MECHANISM OF SUPPORT

A CCNR will use the Center Grant mechanism (P50), which provides support for
multidisciplinary and multi-investigator study of specific research problems of
a complex nature that requires the application of diverse expertise and
methodologies.

Applicants may request support for a period of up to 5 years, followed by a
competitive renewal application for a second five year period.  The NIMH will not
support individual Centers for longer than two consecutive funding periods.  It
is anticipated that individual projects which are developed as outgrowths of a
Center grant will seek independent funding.

An applicant planning to submit an investigator-initiated grant application
requesting $500,000 or more in direct costs for any year is advised that he or
she must contact Institute program staff before submitting the application, i.e,
as plans for the study are being developed.  Furthermore, the applicant must
obtain written agreement from the staff that the Institute will accept the
application for consideration for award.  Finally, the applicant must identify,
in the cover letter that is sent with the application, the program staff member
who and Institute which agreed to accept assignment of the application.

Any application subject to this policy that does not contain the required
information in the cover letter sent with the application will be returned to the
applicant without review.

For additional information concerning large grant applications, see the NIH Guide
dated March 20, 1998.

RESEARCH OBJECTIVES

Background

As research produces ever greater levels of detail in each of the fields that
collectively constitute the neurosciences, the ability of individual
investigators to integrate approaches and disciplines is diminished.  Yet, the
cutting edge of science is often defined across disciplinary boundaries and
through the use of new technologies.  The Conte Centers for Neuroscience
Research(CCNR) will support highly interactive research projects addressing
different aspects of a common set of research issues at different levels of
biological organization and from different disciplinary, methodological and
technological perspectives.  Such integrative approaches will provide unique
opportunities to advance understanding factors that influence the development and
function of the brain, offering new insights to the brain-behavior relationships
and mental illness.

Objectives and Scope

Each CCNR is designed to address a critical question of basic brain research
through a multidisciplinary, well integrated, and highly focused research
program.  A CCNR is characterized as follows:

o  The purpose of a CCNR is to address one specific, well focused research
hypothesis related to brain function.  The research question may be posed in any
area(s) of neuroscience related to the mission of the NIMH.

o  A CCNR should clearly demonstrate a high interdependence of projects and
investigators, and solid evidence of integration across projects.

o  It is expected that a Center will be organized specifically to address
innovative, creative, and potentially high risk/high impact research questions.
Centers must rigorously test the proposed hypothesis and generate new ones. It
is expected that such research will advance a field in fundamental and
significant ways.

o  A CCNR should be based upon a highly integrated multidisciplinary approach
which uses as many disciplines, perspectives, and approaches as are needed and
appropriate to solve the research problem.  The best neuroscience laboratories
and investigators using the most advanced technologies should be enlisted toward
this end.

o  The Center mechanism may not be used as a substitute for individual grant
support. It is, therefore, expected that investigators participating in Centers
will have independent, peer reviewed research support. A Center must be viewed
as a unique scientific opportunity to investigate leading edge research questions
not currently being addressed.

o  The CCNR Director should have a demonstrated capability to organize,
administer and direct the Center.  This individual should be the scientific
leader of the Center, and thus must also head at least one of the projects, with
a minimum total time commitment of 30 percent to the Center.

o  Investigators heading projects in a CCNR should be prominent scientists in
basic neuroscience research. Investigators with the qualifications to contribute
to a unique enterprise such as a CCNR may be located in different geographic
locations. Therefore, collaborations among different institutions are encouraged,
if scientifically appropriate.

o  A CCNR should provide opportunities for young investigators who have the
potential for independent research careers to become skilled in the experimental
strategies, approaches, and techniques of modern neuroscience research.  In
addition, there should be close coordination between the Center and relevant
predoctoral and/or postdoctoral research training programs of the participating
institutions.  Special attention should also be given to the recruitment and
training of minority students.

o  Each CCNR should provide outreach that makes the public aware of the
importance and implications of the CCNR research for addressing basic
neuroscience issues and their relationship to mental illness and mental health.

Research Topics

The following are listed as examples of broad research areas within the NIMH
research mission which are technologically and conceptually timely.  This list
is not meant to be comprehensive, nor are the examples meant to be exclusive of
other topics.

o  Identification of genes that influence the development and function of
receptors, channels, and their transduction mechanisms in synaptic functioning
as a means for better understanding CNS drug actions and for developing new and
more specific drugs

o  Studies combining molecular, cellular, circuit, and behavioral approaches to
elucidate functional organization of systems underlying emotion, cognition,
attention, perception, and language

o  Characterization of structure, function, and development of neural pathways
mediating higher order cognitive functions, including the effects of hormones and
trophic factors and the mechanisms by which such molecules act in relation to
function and plasticity across the lifespan

o  Elucidation of exogenous and endogenous agents that cause cell death, and the
roles that these play in development, plasticity across the lifespan and
behavioral function and dysfunction.

o  Further elucidation of the organization (e.g., connectional, dynamic) and
regulation (e.g., genomic, endocrine, state-dependent) of neural systems
underlying normal behavioral processes such as emotion, perception, cognition,
language, and attention.

Activities Supported

To provide a suitable structure for achieving the objectives of this
announcement, a Center may request funds, in addition to support for the research
projects, as follows:

o  Institutional Environment and Resources:  Funds may be requested for research
resources such as equipment needed to conduct the proposed research, supplies
needed to accomplish the proposed research, incidental alteration or renovation
of facilities consistent with Public Health Service policy, etc.  Strongly
encouraged is the sharing of resources across multiple projects of the center.
Funds provided through Center grants may not be used for support of trainee
stipends, fees, or other expenses directly relating to training activities.

o  Essential Scientific Expertise:  To provide the most effective combination of
scientific skills, applicants may request funds to recruit scientists to augment
or strengthen the skills, expertise, and capabilities of existing staff. 
Although recruitment may take place after the award has been made, the expertise
required, the role in Center activities, and the time to be devoted to the Center
should be provided in the application.  It should be emphasized, however, that
after the award, such individuals may not be recruited to serve as a substitute
for a Project P.I.

o  Annual Meeting: Funds to support travel to the two day Annual Meeting of
Center grantees in the Washington, D.C. area should be included in the budget for
the Center Director and up to three additional key members of the research team.

o  Advisory Board: An external advisory board should serve as an important source
of guidance from eminent researchers who do not have perspectives colored by a
vested interest in either the Center or in the research proposed to be performed
by the Center. To provide a fresh perspective on the science unfolding at a
Center, and to avoid reducing the pool of potential reviewers, applicants should
not identify, choose or contact prospective board members before a funding
decision is made. Applicants may request funds to support travel of board members
for meetings at the end of the second and the end of the fourth year of funding.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

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 have been published in the Federal Register of March 28, 1994
(FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Volume 23,
Number 11, March 18, 1994.

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

NIH POLICY AND GUIDELINES ON THE INCLUSION OF CHILDREN AS PARTICIPANTS IN
RESEARCH INVOLVING HUMAN SUBJECTS

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:
http://www.nih.gov/grants/guide/notice-files/not98-024.html

LETTER OF INTENT

Prospective applicants are asked to submit, by July 1, 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 program
announcement 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 NIMH
staff to estimate the potential review workload and avoid conflict of interest
in the review.

The letter of intent is to be sent to Dr. Michael Huerta, at the address listed
under INQUIRIES.

APPLICATION PROCEDURES

Applications are to be submitted on the grant application form PHS 398 (rev.
5/95) and will be accepted on October 20.  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; fax: (301) 480-0525 Email: [email protected].  The title and number of the
program announcement must be typed in Section 2 on the face page of the
application.

A major requirement for each CCNR is the conduct of multidisciplinary,
integrative research on a single, highly focused research question.  The
application must describe the hypotheses to be tested, and the goals and
approaches for the CCNR.  In addition, the proposal should clearly articulate the
reasons a Center approach is needed for the proposed work as well as the unique
benefits that will accrue from a Center.  It should be emphasized that this
Center mechanism is not meant to be a substitute for individual grant support. 
Therefore, the reasons that constituent projects require CCNR support should be
fully justified.

o  General Description of the Center (Not to exceed 12 pages):

Provide an overview of the entire proposed Center describing the central theme
and goals.  Describe how the overall Center can achieve its major objectives. 
Explain the proposed contribution of each of the projects in achieving the
objectives of the Center.  Furthermore, the administrative arrangements and
support necessary to effect the research should be carefully described in the
application.  Shared resources should be described.  When multiple institutional
sites are involved, a detailed description and supporting documentation for the
cooperative administrative arrangements should be included.  In addition, provide
detailed information on collaborations, recruitment, facilities and resources.

o  Evidence of Feasibility and Preliminary Findings (for new, Type 1,
applications only; not to exceed 6 pages)

Present evidence that the research team will be able to work together to
accomplish the research proposed in the projects, present preliminary results,
present evidence of competence in the areas proposed, etc.

If previously supported by an NIMH Silvio O. Conte Feasibility Center for
Neuroscience Research, indicate the outcome of that activity as it relates to the
application CCNMD support.

o  Progress Report (for competing renewal, Type 2, applications only; not to
exceed 3 pages for each project supported)

Describe the results of projects supported in previous CCNR grant and the manner
in which those results and projects relate to the currently proposed center
application.  Describe the manner in which the center mechanism provided synergy
to the previously funded center.

o  Individual Projects (Not to exceed 10 pages for any one project):

Describe the major objectives and goals of each project, its integration with the
other projects, and its relationship to the overall Center.

Each individual project should also include detailed descriptions on the
following:

a.  Research Plan:  The question to be addressed and the hypothesis to be tested
by the proposed research should be highly focused and fully explained.  Full
discussion is required on the status of current research efforts (both within the
Center and elsewhere) addressing the issue, the limitations of existing
approaches, and why the particular research question lends itself to a
multidisciplinary, integrative approach.

b.  Experimental Plan:  The application will not require extensive details for
individual experiments.  The description of the experimental design should
outline the strategies proposed to accomplish the specific aims of the project,
and should include a discussion of the innovative aspects of the approach. 
However, the experimental procedures need not be spelled out in great detail if
those procedures have already been extensively published and universally accepted
by the scientific community.  Nevertheless, any new methodology and its advantage
over existing methodologies should be fully described.  Furthermore, the
feasibility of the proposed experiments, the potential pitfalls, relevant
alternative approaches should changes become necessary, and their relevance to
the goals of the Center should be fully discussed.  The methods to be used should
be cited and referenced.  It should be emphasized that this necessitates the
inclusion of investigators that are considered to be leaders in their fields and
whose experiments are widely published and accepted by the scientific community.

c.  Operational Plan:  A description of the resources and working arrangements
required to implement the research plan should be fully elaborated.  A detailed
description should be given of all research components.  A distinction must be
made between those resources which are already in place (including staff) and
those resources which must be added to complete the proposed research.  Also
included in this section is the manner in which an external advisory board will
advise the Center.  Nevertheless, prospective board members should not be chosen
or contacted prior to a funding decision, and, therefore, will not be named.

o  Research Career Development and Outreach Plans: A description of the manner
in which Center activities will provide opportunities for young investigators and
how the CCNR relates to existing training programs of participating institutions
should be given.  Also, plans for disseminating information to the public
regarding the activities of the CCNR should be given.

The completed original application and four legible copies must be sent or
delivered to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, one additional copy of the application must be sent
to:

Henry J. Haigler, Ph.D.
Division of Extramural Activities
National Institute of Mental Health
5600 Fishers Lane, Room 9C-18
Rockville, MD  20857

REVIEW CONSIDERATIONS

Applications submitted in response to this program announcement will be reviewed
by the NIMH program staff to determine if they satisfy the objectives and
requirements of a CCNR as outlined in this program announcement (excluding
scientific or technical merit).  Applications that do not meet these objectives
and requirements will not be accepted and will be returned to the applicant.

Applications that are complete will be evaluated for scientific and technical
merit by an appropriate peer review group convened by the NIMH in accordance with
the standard NIH peer review procedures.  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 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, when applicable.

Review Criteria

Criteria for scientific/technical review of Research Center applications will
include the following:

o  Intrinsic merit of the intellectual focus and research: The overall quality,
scientific merit, and innovativeness of the research to be done; the likelihood
that the work will lead to fundamental advances within the field, to new
discoveries, and/or to new technological developments.  In addition, the research
conducted must center around a highly focused and well-defined question.

o  Integration across projects:  The adequacy of the proposed Center to integrate
across research projects so that activities in each project inform and advance
the others.

o  Appropriateness of the Center approach:  The need for and suitability of the
Center approach; whether a Center approach will add significantly to what could
be done through other modes of research support.  In this respect, the
integration of the projects is of utmost importance and should be explicitly
described.

o  Research competence:  The capability and scientific credentials of the Center
Director and constituent project directors and participating scientists, who are
expected to be regarded by their peers as leaders in, and at the forefront of,
their respective fields.

o  Center Director credentials:  Ability of the Center Director to organize,
administer, and direct the Center and, in addition, head at least one of the
proposed projects, be it basic or clinical in nature; devoting a minimum of 30
percent of his/her time to the Center.  The Director must, by necessity, be the
scientific leader of the Center.

o  Institutional commitment:  The nature and level of resource commitments from
the home institution and from other participant institutions; and plans for
interactions with the rest of the sponsoring institution.

o  Appropriateness of management plans and arrangements:  The feasibility and
adequacy of the organizational and administrative plans; the appropriateness of
the budget; and the mechanisms to evaluate the Center's progress.

o   Quality and appropriateness of the outreach and research career development
components of the Center's activities:  The adequacy of approaches used to
disseminate information regarding the Center's activities as they relate to
public understanding of science and mental health and illness.  The likely
effectiveness of approaches to attract and involve young investigators and
students who show potential for significant future contributions and independent
research careers in the work of the Center.

The initial review group will also examine the provisions for the protection of
human and animal subjects, the safety of the research environment, and
conformance with the NIH Guidelines for the Inclusion of Women and Minorities as
Subjects in Clinical Research.

As part of the scientific and technical merit evaluation of the research plan,
reviewers will be instructed to address:

o  Adequacy of plans for including children as appropriate for the scientific
goals of the research, or justification for exclusion.

The initial review group will make an overall recommendation for approval (and
assign a priority score) or disapproval of the entire Center application.  Under
some circumstances, it may be appropriate for the initial review group to
recommend disapproval of one or more project(s).

AWARD CRITERIA

Applications will compete for available funds with all other approved
applications assigned to NIMH.  The following will be considered in making
funding decisions:  Quality of the proposed project as determined by peer review,
availability of funds, and program priority.

Schedule

To ensure a uniform review quality, all applications will be reviewed by a single
review group, which will meet once per year. In accordance with this objective,
there will be one receipt date each year.  Applications received after this date
will be returned to the applicant without review.

Letter of Intent Receipt Date:  July 1
Application Receipt Date:       October 20
Administrative Review:          November
Scientific Review:              April/May
Advisory Council Review:        May/June
Earliest Starting Date:         July

INQUIRIES

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

Direct inquiries regarding programmatic issues to:

Michael F. Huerta, Ph.D.
Division of Basic and Clinical Neuroscience Research
National Institute of Mental Health
Parklawn Building, Room 11-103
Rockville, MD  20857
Telephone:  (301) 443-3563
FAX:  (301) 443-1731
Email:  [email protected]

Direct inquiries regarding fiscal matters to:

Diana S. Trunnell
Grants Management Branch
National Institute of Mental Health
Parklawn Building, Room 7C-08
Rockville, MD  20857
Telephone: (301) 443-2805
FAX:  (301) 443-6885
Email:  [email protected]

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No.
93.242. 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. 
Awards will be administered under PHS grants policy as stated in the Public
Health Service Grants Policy Statement (April 1, 1994).

PHS strongly encourages all grant and contract recipients to provide a smoke-free
workplace and promote the nonuse 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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