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RESEARCH COLLABORATIONS TO PROVIDE 900 MHZ NMR SPECTROSCOPY
 
RELEASE DATE:  June 25, 2002
 
RFA: GM-03-001
 
National Institute of General Medical Sciences (NIGMS)
(http://www.nigms.nih.gov) 

LETTER OF INTENT RECEIPT DATE:  October 15, 2002

APPLICATION RECEIPT DATE:  November 15, 2002  
 
THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA 

The purpose of this RFA is to re-announce the National Institute of 
General Medical Sciences (NIGMS) program to create "Research 
Collaborations to Provide 900 MHz NMR Spectroscopy," last issued as 
GM-01-005 in July 2001.  The 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. 
 
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 structure and behavior of new 
categories of biological macromolecules, 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 and RNA folding, 
protein-protein and protein-nucleic acid complex formation, and 
binding-induced conformational change.  These processes are key to 
normal biological function and regulation and are critically 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 program is to provide ultra-high field NMR 
spectrometers to groups of NIGMS-funded investigators so they can solve 
significant and challenging biological problems.  In addition, NIGMS 
expects 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. 

The projects of the collaborating investigators should be of great 
biomedical importance, and have pressing need for the new spectrometer, 
but they need not be closely integrated according to research topic.  
Rather, the collaborators should identify a common vision of how NMR 
spectroscopy at ultra-high field can best be applied and advanced to 
provide a qualitative improvement in our ability to observe and 
understand critical biomolecular events.
 
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.  As an applicant you will be solely 
responsible for planning, directing, and executing the proposed 
project.  This RFA is a one-time solicitation.  Future unsolicited, 
competing-continuation applications for operational expenses will 
compete with all investigator-initiated applications and will be 
reviewed according to the customary peer review procedures.  The 
anticipated award date is July 1, 2003.

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 no more than 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.
 
FUNDS AVAILABLE
 
NIGMS intends to commit approximately $11 million dollars total costs 
in FY 2003 and $0.6 million total cost per annum in FY 2004-2007 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.
 
ELIGIBLE INSTITUTIONS
 
You may submit an application if your institution is domestic and has 
any of the following characteristics: 

o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, 
hospitals, and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  

Under this funding mechanism, foreign institutions are not eligible to 
apply.
 
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS   

The NMR spectrometers funded via this initiative are intended to 
facilitate research in scientific areas of interest to NIGMS. Only a 
Principal Investigator (PI) of an NIGMS-funded R01, R37, or P01 grant 
with one or more years of support remaining at the time of award can 
serve as the PI.  A majority of the collaborating investigators must 
also have funding from the NIGMS.  Other collaborators must have 
externally peer-reviewed research funding in areas 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.
 
SPECIAL REQUIREMENTS 

Three-dimensional structures of biomacromolecules determined in whole 
or in part using these spectrometers 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.
 
WHERE TO SEND INQUIRIES

Applications submitted under this RFA will not be accepted without the 
prior approval of NIGMS.  Inquiries are strongly encouraged and may 
fall into three areas:  scientific/research, peer review, and financial 
or grants management issues.

o Direct your questions about scientific/research issues to:

Janna P. Wehrle, Ph.D.
Division of Cell Biology and Biophysics
National Institute of General Medical Sciences
Building 45, Room 2AS.19K  MSC 6200
Bethesda, MD  20892
Telephone:  (301) 594-5950
FAX:  (301) 480-2004
Email:  [email protected] 

o Direct your questions about peer review issues to:

John Bowers, Ph.D.
Center for Scientific Review
6701 Rockledge Drive, Room 4168 
Bethesda, MD  20892-7710
Telephone:  (301) 435-1725
Email:  [email protected] 

o Direct your questions about financial or grants management matters 
to:

Joe Ellis
Grants Management Officer
National Institute of General Medical Sciences
Building 45, Room 2AN.32C MSC 6200
Bethesda, MD  20892
Telephone:  (301) 594-5510
FAX:  (301) 480-1969
Email:  [email protected] 
 
LETTER OF INTENT
 
Prospective applicants are asked to submit a letter of intent that 
includes the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o 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 staff to estimate 
the potential review workload and plan the review.
 
The letter of intent is to be sent by the date listed at the beginning 
of this document.  The letter of intent should be sent to:

Janna P. Wehrle, Ph.D.
Division of Cell Biology and Biophysics
National Institute of General Medical Sciences
Building 45, Room 2AS.19K  MSC 6200
Bethesda, MD  20892
Telephone:  (301) 594-5950
FAX:  (301) 480-2004
Email:  [email protected]

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001).  The PHS 398 is 
available at http://grants.nih.gov/grants/funding/phs398/phs398.html in 
an interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 710-0267, Email: [email protected].
 
SUPPLEMENTAL INSTRUCTIONS

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 can maximally benefit from use of the ultra-high field 
spectrometer and should provide an organizational plan for selecting 
projects 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.  

To facilitate the review process, potential members of any external 
advisory or similar committees proposed 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. 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. 

USING THE RFA LABEL:  The RFA label available in the PHS 398 (rev. 
5/2001) 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 RFA 
label is also available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
 
SENDING AN APPLICATION TO THE NIH:  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)
 
APPLICATION PROCESSING:  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.

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR 
and for responsiveness by the NIGMS. Incomplete 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:

o Receive a written critique
o Receive a second level review by the National Advisory General 
Medical Sciences 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 your application in order to judge the likelihood 
that the proposed research will have a substantial impact on the 
pursuit of these goals: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
  
The scientific review group will address and consider each of these 
criteria in assigning your application"s overall score, weighting them 
as appropriate for each application.  Your 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, 
you may propose to carry out important work that by its nature is not 
innovative but is essential to move a field forward.

(1) SIGNIFICANCE:  Does your study address an important problem? If the 
aims of your application are achieved, how do they advance scientific 
knowledge?  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 systems or of broader categories 
of important biological molecules?

(2) APPROACH:  Are the conceptual framework, design, methods, and 
analyses adequately developed, well integrated, and appropriate to the 
aims of the project?  Do you acknowledge potential problem areas and 
consider alternative tactics?  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?  

(3) INNOVATION:  Does your project employ novel concepts, approaches or 
methods? Are the aims original and innovative?  Does your project 
develop new methodologies or technologies? Is the technical development 
you propose likely to provide fundamentally new approaches to 
macromolecular characterization?

(4) INVESTIGATOR:  Are you 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 your work 
will be done contribute to the probability of success?  Do the proposed 
experiments take advantage of unique features of the scientific 
environment and employ useful collaborative arrangements?  Is there 
adequate evidence of institutional support?  Is the physical 
environment adequate to support the spectrometer and the proposed 
research activities?

ADDITIONAL REVIEW CRITERIA:  In addition to the above criteria, your 
application will also be reviewed with respect to the following:

o PROTECTIONS:  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 DATA SHARING:  The adequacy of the proposed plan to share data. 

o BUDGET:  The reasonableness of the proposed budget and the requested 
period of support in relation to the proposed research.

o OTHER 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 you will use in selecting future projects.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:  October 15, 2002
Application Receipt Date:  November 15, 2002
Peer Review Date:  February-March, 2003
Council Review:  May, 2003
Earliest Anticipated Start Date:  July 1, 2003

AWARD CRITERIA

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.
 
REQUIRED FEDERAL CITATIONS 

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 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.

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. Furthermore, we caution reviewers that their anonymity 
may be compromised when they directly access an Internet site.

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 RFA 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.

AUTHORITY AND REGULATIONS:  This program is described in the Catalog of 
Federal Domestic Assistance No. 93.821, and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or 
Health Systems Agency review.  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 described at 
http://grants.nih.gov/grants/policy/policy.htm  and under Federal 
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. 

The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and discourage the 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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