RESEARCH COLLABORATIONS TO PROVIDE 900 MHZ NMR SPECTROSCOPY

Release Date:  June 20, 2001

RFA:  RFA-GM-01-005

National Institute of General Medical Sciences
 (http://www.nigms.nih.gov)

Letter of Intent Receipt Date:  October 15, 2001
Application Receipt Date:       November 15, 2001

PURPOSE

The National Institute of General Medical Sciences (NIGMS) believes that 
nuclear magnetic resonance (NMR) spectrometers operating at field strengths of 
900 MHz (21.1T) or higher have the potential to dramatically improve our 
understanding of the structure and dynamics of proteins, nucleic acids, and 
other biological macromolecules.  The purpose of this program is to provide 
shared access to ultra-high field-strength NMR spectrometers for groups of 
NIGMS-funded investigators studying challenging biological problems that can 
uniquely benefit from the use of ultra-high field NMR spectroscopy.   In 
addition, it is expected that by working together these groups of 
investigators will create new methods that will further expand the power of 
NMR spectroscopy to describe important biological molecules and events.  

HEALTHY PEOPLE 2010

The Public Health Service (PHS) is committed to achieving the health promotion 
and disease prevention objectives of "Healthy People 2010," a PHS-led national 
activity for setting priority areas.  This Request for Applications (RFA), 
Research Collaborations To Provide 900 MHZ NMR Spectroscopy, is related to one 
or more of the priority areas.  Potential applicants may obtain a copy of 
"Healthy People 2010" at http://www.health.gov/healthypeople/.

ELIGIBILITY REQUIREMENTS

The NMR spectroscopy resources funded via this initiative are intended to 
facilitate research in scientific areas of interest to NIGMS.  Potential 
applicants should visit the NIGMS web site at http://www.nigms.nih.gov for 
detailed information.  Consistent with NIH policy for applications that will 
exceed $500,000 in direct costs in one year, applications submitted under this 
RFA will not be accepted without the prior approval of NIGMS.   

Only Principal Investigators (PIs) of NIGMS-funded R01, R37, or P01 grants 
with one or more years of support remaining at the time of award can serve as 
the PI of an NIGMS-funded NMR spectroscopy resource.  A majority of the 
collaborating investigators must also have funding from the NIGMS.  Other 
collaborators must have externally peer-reviewed research funding.  Their 
projects should be consistent with the NIGMS mission.  Scientific areas 
supported by NIGMS are described on our web site at 
http://www.nigms.nih.gov/about_nigms/overview.html.

Applications may be submitted by domestic, 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.  Applications from foreign 
institutions and from for-profit organizations will not be accepted. 

MECHANISM OF SUPPORT

This RFA uses the National Institutes of Health (NIH) P41 Biotechnology 
Resource Grant mechanism, which is used by the NIGMS to make extraordinary 
research instrumentation available to organized groups of our investigators 
for the solution of significant and challenging problems in biomedical 
research.

An applicant may request no more than $5 million in direct costs in the first 
year for the purchase of an NMR spectrometer with a field strength of 21T or 
greater.  In addition, up to $200,000 in direct costs per year for five years 
may be requested for continuing support of the spectrometer and operation of 
the resource.  The budget might include items such as:

o Salaries for personnel responsible for technical development, spectrometer 
installation, maintenance, upgrade, and programming, or assistance and 
training of collaborators.

o Salaries for individuals, including the PI, responsible for the organization 
and operation of the resource.

o Spectrometer hardware and software. 

o Supplies such as cryogens, sample holders, and electronic storage media.

o Establishment of computer systems to allow remote operation and facilitate 
collaboration.

Funds provided via this program are not intended to support the individual 
research projects which use the spectrometers.  These should be supported by 
independent peer-reviewed funding to the collaborators.  Funds will not be 
provided for the selection, construction, or renovation of a site for the 
spectrometer.  Responsibility for the planning, direction, and execution of 
the proposed project, including appropriate siting, will be solely that of the 
applicant.
 
The total project period proposed in an application submitted in response to 
this RFA may not exceed five years.  Future unsolicited competing continuation 
applications for operational expenses will compete with all investigator-
initiated applications and be reviewed according to the customary peer review 
procedures.  The anticipated award date is July 1, 2002.

FUNDS AVAILABLE 

NIGMS intends to commit approximately $11 million dollars total costs in FY 
2002 and $0.6 million total cost per annum in FY 2003-2006 to fund one to 
three new grants in response to this RFA.  Because the nature and scope of the 
requests may vary, the size of awards may vary.  Although the financial plans 
of the NIGMS provide support for this program, awards pursuant to this RFA are 
contingent upon the availability of funds and the receipt of a sufficient 
number of meritorious applications.  At this time, it is not anticipated that 
this RFA will be reissued.

RESEARCH OBJECTIVES

Background and Rationale

Recent breakthroughs in the design and execution of NMR experiments and in the 
analysis and interpretation of NMR data have created the possibility of 
determining the solution structures and behavior of new categories of 
biomolecules, including larger proteins, macromolecular complexes, 
glycoproteins and glycolipids.  Moreover, NMR spectroscopic methods are now 
being developed that can describe--in atomic detail--dynamic processes such as 
protein folding, protein-protein binding, and binding-induced conformational 
changes, that are key to normal biological function and regulation and also 
intimately involved in disease processes and drug response.  NMR experiments 
capable of attacking these more challenging targets have a particular need for 
higher magnetic field strength.  Access to next-generation NMR spectrometers 
for NIGMS-funded researchers will dramatically advance our understanding of a 
wide range of vital physiological and pathological phenomena.

Objectives

The purpose of this announcement is to provide NMR spectrometers of 21T or 
greater to collaborative groups of NIGMS-funded investigators who have 
challenging biological problems that require the special advantages of ultra-
high field NMR spectroscopy.  In addition, it is expected that these 
collaborations will lead to the design and implementation of novel NMR 
experiments capable of providing insights beyond those that can be predicted 
from current knowledge. 

It is not required that the projects of collaborating investigators be closely 
integrated according to a research topic.  Rather, it is expected that the 
collaborators will share a common vision of how NMR spectroscopy at ultra-high 
field can be applied and advanced to provide a qualitative improvement in our 
ability to understand critical biomolecular events.

SPECIAL REQUIREMENTS

Determination of three-dimensional structures of biomacromolecules by any 
individual, whether a collaborator or other user, will be subject to the NIH 
rules for deposition and release of structure information via the Protein Data 
Base and the BioMagResBank, 
http://grants.nih.gov/grants/guide/notice-files/not99-010.html, 
regardless of the source of funding for the project.  
This policy requires free release of atomic coordinates and other necessary 
data immediately upon publication.

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 sub-populations must be included in all NIH-supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification are provided indicating 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 
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research," published in the NIH Guide for Grants and Contracts on 
August 2, 2000 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); 
a complete copy of the updated Guidelines are available at  
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm:  The 
revisions relate to NIH defined Phase III clinical trials and require: a) all 
applications or proposals and/or protocols to provide a description of plans 
to conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups if applicable; and b) all 
investigators to report accrual, and to conduct and report analyses, as 
appropriate, by sex/gender and/or racial/ethnic group differences.

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://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.

URLS IN NIH GRANT APPLICATIONS OR APPENDICES

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

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT

The Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances. Data that are (1) first produced in a project 
that is supported in whole or in part with Federal funds and (2) cited 
publicly and officially by a Federal agency in support of an action that has 
the force and effect of law (i.e., a regulation) may be accessed through FOIA. 
It is important for applicants to understand the basic scope of this 
amendment. NIH has provided guidance at: 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this RFA (PA) in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time. If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the application. 
In addition, applicants should think about how to structure informed consent 
statements and other human subjects procedures given the potential for wider 
use of data collected under this award.

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that includes a 
descriptive title of the proposed research resource, 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 this 
RFA.   

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 Center for Scientific Review (CSR) staff to estimate the 
potential review workload and plan the review.  The letter of intent is to be 
sent to the program official named at the end of this RFA by the letter of 
intent receipt date listed in the heading.

APPLICATION PROCEDURES

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 301/435-0714, email: 
GrantsInfo@nih.gov.

The application must document a clear plan for operation of the research 
facility and for exploitation of the unique capabilities of the 900 MHz 
spectrometer to advance biomedical science.  It should describe a complete 
plan for selecting and purchasing a spectrometer, including the physical plan 
for siting, installation, and operation of the spectrometer.  The resources 
and environment available to support both the requested instrument and any 
necessary on-site research activities should be itemized.  Any plans for 
remote execution of NMR experiments should be described in detail.

The application should list the criteria that will be used to identify 
projects that will maximally benefit from use of the ultra-high field 
spectrometer and should provide an organizational plan for selecting, and 
allocating instrument time.  Descriptions of already funded collaborative 
projects should be brief and should emphasize the novel information that will 
be provided by the ultra-high field NMR spectrometer, compared with that 
obtained using conventional instruments.  A process for adding and terminating 
projects should be laid out.  Plans for development of novel experiments, 
hardware, or software should be described in detail.  Do not exceed 25 pages 
for items a-d of the Research Plan. 

The written application should be complete.  It is not anticipated that an 
applicant interview will be a part of the review process.  Appendices may be 
included, following the instructions for unsolicited applications described in 
form PHS 398.  To facilitate the review process, potential members of external 
advisory or similar committees should not be approached prior to award, nor 
identified in the letter of intent or application.  The roles and functions of 
any such committees should be described in concept only.

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.  Type the RFA 
number on the label.  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.

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

Submit a signed, typewritten original of the application, including the 
Checklist, and five signed photocopies plus five sets of appendix material, in 
one package, 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)

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

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

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NIGMS.  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 
the Center for Scientific Review in accordance with the review criteria stated 
below.  As part of the initial merit review, all applications will receive a 
written critique and undergo a process in which only those applications deemed 
to have the highest scientific merit, generally the top half of the 
applications under review, will be discussed, assigned a priority score, and 
receive a second level review by the National General Medical Sciences 
Advisory Council.

Review Criteria

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments reviewers will be asked to discuss the following aspects 
of the application in order to judge the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals.  Each of these 
criteria will be addressed and considered in assigning the overall score, 
weighting them as appropriate for each application.  Note that the application 
does not need to be strong in all categories to be judged likely to have major 
scientific impact and thus deserve a high priority score.  For example, an 
investigator may propose to carry out important work that by its nature is not 
innovative but is essential to move a field forward.

(1) Significance:  Do the studies proposed address important problems?  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?  Will the added information provided by the 900 MHz 
spectrometer make a fundamental difference in our understanding of the 
specific target system or of broader categories of important biological target 
molecules?

(2) Approach:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project?  Are the organizational and decision-making structures well-designed 
to promote collaboration?  Are the technical foundations of novel methods to 
be developed well-reasoned and sound?  Does the applicant acknowledge 
potential problem areas and consider alternative tactics?

(3) Innovation:  Do the studies employ novel approaches or methods?  Is the 
technical development likely to provide fundamentally new approaches to 
macromolecular characterization?

(4) Investigator:  Is the investigator appropriately trained and well suited 
to direct this resource, both scientifically and organizationally?  Do the 
collaborators have the appropriate biological and technical expertise to fully 
exploit and expand the potential of the instrument?  

(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 adequate evidence of 
institutional support?  Is the physical environment adequate to support the 
proposed activities?

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

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

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

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

o  The adequacy of the proposed plan to share data, if appropriate.

Additional Review Criteria

The scientific merit of the already funded collaborative projects will not be 
re-reviewed.  Reviewers will assess the extent to which these projects will 
significantly benefit from the availability of the resource.  The 
collaborative projects proposed in the application will be considered an 
indication of the criteria and judgment that will be used in selecting future 
projects. 

Schedule  

Letter of Intent Receipt Date:    October 15, 2001
Application Receipt Date:         November 15, 2001
Peer Review Date:                 February-March, 2002
Council Review:                   May, 2002
Earliest Anticipated Start Date:  July, 2002

AWARD CRITERIA

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 institutional commitment

INQUIRIES

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

Direct inquiries regarding programmatic issues to:

Janna P. Wehrle, Ph.D.
Division of Cell Biology and Biophysics
National Institute of General Medical Sciences
Natcher Building, Room 2AS.19K MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-5950
FAX:  301-480-2004
Email:  wehrlej@nigms.nih.gov

Direct inquiries regarding review issues to:

John Bowers, Ph.D.
Center for Scientific Review
6701 Rockledge Drive, Rm. 4168 
Bethesda, MD  20892-7710
Telephone: (301)435-1725
Email: bowersj@csr.nih.gov

Direct inquiries regarding fiscal matters to:

Joe Ellis
Grants Management Officer
National Institute of General Medical Sciences 
Natcher Building, Room 2AN.32 MSC 6200
Bethesda, MD  20892-6200
Telephone: (301) 594-5510
FAX: (301)480-1969
Email:  ellisj@nigms.nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.821.  Awards are made under authorization of Sections 301 and 405 of the 
Public Health Service Act as amended (42 USC 241 and 284) and administered 
under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 
74 and 92.  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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