Full Text AA-96-002
 
ANTIBODIES AND ALCOHOL-RELATED BEHAVIOR
 
NIH GUIDE, Volume 25, Number 10, March 29, 1996
 
RFA:  AA-96-002
 
P.T. 34

Keywords: 
  Alcohol/Alcoholism 
  Neurotransmitters 
  Receptors 

 
National Institute on Alcohol Abuse and Alcoholism
 
Letter of Intent Receipt Date:  May 13, 1996
Application Receipt Date:  June 13, 1996
 
PURPOSE
 
The National Institute on Alcohol Abuse and Alcoholism (NIAAA) seeks
research applications aimed at developing antibodies to proteins
mediating alcohol-related behaviors.  This Request for Applications
(RFA) invites research applications that develop and utilize such
antibodies to study the effects of ethanol on neurotransmitter
receptor subtypes and second messenger proteins and on
phosphorylation states involved in the actions of ethanol.
Applications should develop and characterize highly specific
antibodies to determine the distribution of the subunits in specific
cell types, neural pathways, and brain regions known for their
ethanol sensitivity.
 
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 RFA,
Antibodies and Alcohol-Related Behavior, is related to the priority
areas of alcohol abuse reduction and alcoholism treatment.  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, D.C. 20402-9325 (Telephone:
202-512-1800).
 
ELIGIBILITY
 
Applications may be submitted by domestic and foreign, for-profit and
non-profit, public and private organizations, 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.
 
MECHANISM OF SUPPORT
 
Research support may be obtained through applications for a regular
research project grant (R01) for up to five years.  In FY 1995, the
average total cost per year for new R01s funded by NIAAA was
approximately $200,000.  Because the nature and scope of the research
proposed in response to this RFA may vary, it is anticipated that the
size of an award will vary also.  Program project grant applications
(P01) will not be accepted for this RFA.
 
Applicants may submit applications for Investigator-Initiated
Interactive Research Project Grants (IRPGs).  Interactive Research
Project Grants require the coordinated submission of related research
project grant (R01) and, to a limited extent FIRST Award (R29)
applications 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 and
R29 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 under
INQUIRIES.  Further information on the IRPG mechanism is available in
program announcement PA-96-001, NIH Guide for Grants and Contracts,
Vol. 24, No. 35, October 6, 1995.
 
FUNDS AVAILABLE
 
It is estimated that up to $1.4 million will be available for
approximately six to seven grants under this RFA in FY 1996.  This
level of support is dependent on the receipt of sufficient number of
applications of high scientific merit.  Although this program is
provided for in the financial plan of NIAAA, the award of grants
pursuant to this RFA is also contingent upon the availability of
funds for this purpose.  The earliest possible award date is
September 30, 1996.
 
RESEARCH OBJECTIVES
 
Alcohol has the unique characteristic of being a very simple water-
soluble molecule that interacts with specific hydrophobic domains of
important proteins to alter their normal function.  Such actions of
alcohol on single molecules perturb the inter- and intracellular
signaling systems containing those molecules and thereby exert
diverse and profound effects on neural responses.  As a result,
ethanol is known to alter the activity of a variety of processes
involved in synaptic transmission.  Many studies indicate that
ethanol acts directly on neurotransmitter receptors and second
messenger proteins, thereby altering the normal neuronal activity.
Proteins of interest include gamma-aminobutyric acid (GABA),
glutamate (both the NMDA and AMPA types), serotonin, and dopamine
receptors and cyclases, G-proteins, and protein kinases involved in
signal transduction.
 
Many of the proteins affected by ethanol are complex macromolecular
proteins with numerous subtypes containing multiple subunits.  Some
protein assemblies are more sensitive to ethanol than others, such as
observed for GABA and NMDA receptors.  It is hypothesized that the
subunit composition of the receptors in the brain is important in
determining ethanol sensitivity.  Unfortunately, sufficient probes
are not available for studying all of the subunits and in sufficient
quantities to make progress in determining the influence of each
subunit in different regions of the brain.  In addition, the
phosphorylation state of the protein may be of crucial importance in
the actions of ethanol on the protein.  Knowing the specific receptor
subtypes and phosphorylation states involved in ethanol actions,
especially the distribution of the subunits and subtypes in specific
nuclei, neural pathways, and brain regions known for their alcohol
sensitivity, will provide a basis for rational medications
development for treatment of ethanol-induced behaviors.
 
Applications are encouraged to develop and produce antibodies as
probes for identifying subunits of relevant ethanol-affected proteins
in the brain that are not presently available or only in limited
quantities. Applicants may undertake the development of specific
antibodies or utilize antibodies obtained through subcontracts in
exploring the properties of specified neuronal proteins.
Applications should provide a means of producing the antibodies, as
well as propose measures to ensure quality control, including
specificity and cross-reactivity of the products.  In addition,
applicants are encouraged to develop monoclonal versions of the
antibodies, to ensure batch-to-batch uniformity.
 
SPECIAL REQUIREMENTS
 
Since a purpose of this RFA is to provide unique sets of antibodies
to NIAAA-funded researchers who are unable to obtain them for
themselves, antibodies developed in this initiative should be made
available to other investigators by an approved distribution plan in
accordance with the "NIAAA Policy on Distribution of Unique Research
Resources Produced with NIAAA Funding," and the PHS Policy Relating
to Distribution of Unique Research Resources Produced with PHS
Funding (NIH Guide, Volume 23, Number 26, July 15, 1994).  Indication
of the intent to comply with these policies will be considered in the
Institute's award decisions.
 
LETTER OF INTENT
 
Prospective applicants are asked to submit, by May 13, 1996, 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 of 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 NIAAA
staff to estimate the potential review workload and avoid conflict of
interest in the review.
 
The letter of intent is to be sent to:
 
RFA-AA-96-002
Office of Scientific Affairs
National Institute on Alcohol Abuse and Alcoholism
Willco Building, Suite 409
6000 Executive Boulevard MSC 7003
Bethesda, MD  20892-7003
FAX:  (301) 443-6077
 
APPLICATION PROCEDURES
 
The research grant application form PHS 398 (rev. 5/95) is to be used
in applying for these grants.  Applications kits are available at
most institutional offices of sponsored research and may be obtained
from the Grants Information Office, Office of Extramural Outreach and
Information Resources, National Institutes of Health, 6701 Rockledge
Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/710-0267,
email:  ASKNIH@odrockm1.od.nih.gov; and from NIAAA staff listed under
INQUIRIES.
 
The RFA label available in the PHS 398 (rev. 5/95) 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 marked.  Page limits and limits on size of type are strictly
enforced.  Non-conforming applications will be returned without being
reviewed.
 
Submit a signed, typewritten original of the application, including
the checklist and three signed photo copies in one package to:
 
DIVISION OF RESEARCH GRANTS
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, two additional copies of the application
must also be sent to:
 
RFA AA-96-002
Office of Scientific Affairs
National Institute on Alcohol Abuse and Alcoholism
Willco Building, Room 409
6000 Executive Boulevard, MSC 7003
Bethesda, MD  20892-7003
Rockville, MD  20852 (for express/courier service)
FAX:  (301) 443-6077
 
Failure to forward the above two applications to NIAAA at the above
address may delay consideration of an application such that it may
not be received in time for FY 1996 funding consideration.
 
Applications must be received by June 13, 1996.  If an application is
received after that date, it will be returned to the applicant
without review.  The Division of Research Grants (DRG) 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 DRG 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.
 
REVIEW CONSIDERATIONS
 
Upon receipt, applications will be reviewed for completeness by DRG
and for responsiveness by the NIAAA.  Incomplete applications will be
returned to the applicant without further consideration.  If the
application is not responsive to the RFA, DRG 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 applications under review, will be
discussed, assigned a priority score, and receive a second level
review by the appropriate national advisory council or board.  The
second level of review will be provided by the National Advisory
Council on Alcohol Abuse and Alcoholism.
 
Review Criteria
 
Criteria to be used in the scientific and technical merit review of
the research grant applications will include the following:
 
1. The scientific, technical, or medical significance and originality
of the proposed research.
 
2. The appropriateness and adequacy of the experimental approach and
methodology, including adequacy of quality control methods, proposed
to carry out the research.
 
3. The adequacy of the qualifications (including level of education
and training) and relevant research experience of the principal
investigator and key research personnel.
 
4. The availability of adequate facilities, general environment for
the conduct of the proposed research, other resources, and
collaborative arrangements necessary for the research.
 
5. The reasonableness of budget estimates and duration for the
proposed research.
 
6. Where applicable, the adequacy of procedures to protect or
minimize effects on animal subjects and the environment.
 
AWARD CRITERIA
 
Applications recommended for approval by the National Advisory
Council on Alcohol Abuse and Alcoholism will be considered for
funding on the basis of the overall scientific and technical merit of
the application as determined by peer review, NIAAA programmatic
needs and balance, adequacy of plans for sharing antibodies with
other investigators, and the availability of funds.
 
INQUIRIES
 
Potential applicants are strongly encouraged to seek preapplication
consultation, for which purpose they may contact the individuals
listed below.
 
Direct inquiries regarding the proposed research to:
 
Walter A. Hunt, Ph.D.
Division of Basic Research
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard  MSC 7003
Bethesda, MD  20892-7003
Telephone:  (301) 443-4223
FAX:  (301) 594-0673
Email:  whunt@willco.niaaa.nih.gov
 
Direct inquiries regarding fiscal matters to:
 
Joseph Weeda
Office of Planning and Resource Management
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard MSC 7003
Bethesda, MD  20892-7003
Telephone:  (301) 443-4703
FAX:  (301) 443-3891
Email:  jweeda@willco.niaaa.nih.gov
 
AUTHORITY AND REGULATIONS
 
This program is described in the Catalog of Federal Domestic
Assistance, No. 93.273.  Awards are made under the authorization of
the Public Health Service Act, Sections 301 and 464H, and
administered under the PHS policies and Federal Regulations at Title
42 CFR Part 52, "Grants for Research Projects;" Title 45 CFR Parts 74
and 92, "Administration of Grants;" and 45 CFR Part 46, "Protections
of Human Subjects."  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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