Supplements
for the Determination of High-Resolution Structures
This
announcement was electronically transmitted to DCB/NCI principal investigators
on April 9, 2003. It did not
appear in the NIH Guide for Grants and Contracts.
Purpose
The NCI is
committed to understanding the basic molecular mechanisms involved in the
initiation and development of cancer. In
furtherance of this goal, the Institute supports many investigator-initiated
projects examining a variety of systems relevant to malignant processes. It is increasingly common for an investigator
studying a specific biological system to obtain samples suitable for
high-resolution structure studies even though structure determination was not
the focus of the original research. Once sufficient preliminary data are
attained, such as diffraction-quality crystals for crystallographic data
collection or a resolvable 2-D NMR spectrum, the structural studies are then
often pursued in collaboration with another investigator with an established
structural biology laboratory. On many occasions, preliminary data will be
sufficient to justify the funding of a research grant aimed at structure
determination, but a high-resolution structure, once crystals or spectra are available,
can often be completed quickly, and in many instances sooner than the
completion of the normal grant review process.
The purpose of this supplemental grant program is to expeditiously
provide funds to investigators with demonstrated cancer-relevant molecules, who
have existing NCI research grants and limited or no other support, to complete
the high-resolution structure.
Preliminary data, along with the biological significance of the
molecule, will be considered.
Eligibility
Requirements
The
principal investigator must have an active individual investigator-initiated
research award funded by the Division of Cancer Biology, NCI to study
biological processes where the primary focus is frequently not structural
biology. This announcement is limited to
the R01, P01, R21 and R33 mechanisms. Principal
investigators are strongly encouraged to contact their program director to
discuss their eligibility (see Inquiries section below). In all cases, the
parent grant must have at least one year of support remaining at the time of
the supplemental award. Each parent grant may have only one supplemental award
under this program at a time.
Mechanism
of Support
It is
anticipated that awards will be for activities that are within the general
scope of the parent grant. Therefore, awards will be made via administrative
supplements in amounts up to $40,000 in direct costs for one year, rather than
as competitive supplements. These are
anticipated to be one-time awards.
Program
Objectives
It is the
objective of this program announcement to provide an efficient, cost-effective
funding mechanism to facilitate and encourage the determination of structures
of biological macromolecules once sufficient preliminary data on biological
significance has been obtained to justify their further characterization.
Studies of biological processes increasingly lead to questions about mechanism
and structure that require detailed knowledge of the three-dimensional
structures of the biological macromolecules involved. The determination of
these structures initially depends on the uncertain processes of obtaining
diffraction-quality crystals or resolvable NMR spectra. Many of the
investigators funded to study biological processes attempt crystallization of
the macromolecules involved in the system under investigation or try to obtain
resolvable multi-dimensional NMR spectra as a side aim of the funded research
project. When this aspect is successful, additional grant support is often
required for the completion of the structural studies. Such applications for research support are
often successful since diffraction-quality crystals or a resolvable 2-D NMR
spectrum are generally sufficient to demonstrate feasibility, but processing these
applications can take close to a year from submission to final award. In other cases, initial purification is
exceedingly time consuming and/or expensive, and supplemental funds are needed
to assist the investigator(s) in obtaining sufficient material for
crystallization, NMR characterization, or other structural determinations. Nonetheless, once these preliminary data are
obtained, the completion of the structure can occur rapidly when the principal
investigator has the appropriate expertise or engages in a collaboration with
an established structural biology laboratory. Thus, the supplemental grant
approach announced here is an efficient mechanism of supporting structural
studies since it builds on or may include existing efforts of expression and
purification of the macromolecule under investigation.
Special
Requirements
A progress
report detailing the results of the project will be required as part of the
non-competing application (type 5) or included in the final progress report as
a part of the close-out package if there is no non-competing application.
Application
Procedures
Currently,
support for these supplements is limited to fiscal year 2003. In making requests, the grantee institution,
on behalf of the principal investigator of the parent grant, must submit the
request for supplemental funds directly to NCI. The request is not to be
submitted to the NIH Center
for Scientific Review. The deadline for
submission of applications is June 23,
2003.
Requests
for supplemental support may be submitted by letter, cosigned by an
institutional grants official as described below. The application cannot exceed 5 pages,
excluding other support and letters of commitment from consultants or
collaborators.
The original and three copies should be submitted to Dr.
Randy Knowlton at:
National
Cancer Institute, Division of Cancer Biology
EPN Suite
5000 MSC 7398
Bethesda,
MD 20892-7398
The
application should contain a face page, abstract page, and budget page.
Justification for the budget should be submitted on a separate page (up to $40,000
direct costs may be requested). Information regarding active or pending sources
of project-specific support available to the principal investigator or
collaborators, whether related to this application or not, should be included. The
proposal should be no longer than 5 pages, excluding the budget page and
supporting documents. Letters of commitment from consultants or collaborators,
if any, must be submitted with the application. The name of the DCB Program Director and the
grant number of the parent grant should be included in the cover letter
submitted with the application.
The application should include a brief
description of the project; background information regarding the importance of
the cancer-relevant structure, especially in the context of other structural
information available on similar biological molecules; preliminary data
(diffraction pattern, 2-D NMR spectrum functional verification); plans for the
completion of the structure; and demonstration of adequate expertise, either on
the part of the principal investigator or a collaborator.
Review Considerations
Upon
receipt, applications will be reviewed for completeness by NCI staff.
Incomplete applications will be returned without review. Applications that are complete and responsive
to the program announcement will be evaluated for scientific and technical
merit through an NCI staff review, applying the following general criteria:
- scientific,
technical, or medical significance of the proposed research;
- appropriateness
and adequacy of the experimental approach and methodology to carry out the research;
- qualifications
and research experience of the principal investigator, collaborator, and
staff, particularly, but not exclusively, in the area of the proposed
research;
- availability
of the resources necessary to perform the research;
- Appropriateness
of the proposed budget and duration in relation to the proposed research.
Award
Criteria
It is
expected that awards will be made within three months of submission. The award
will be based on:
- the
importance of the structure;
- qualifications
and research experience of the principal investigator and of the proposed
collaborator(s);
- other
support available to the principal investigator and collaborator;
- availability
of funds.
Inquiries
Inquiries
are encouraged. The opportunity to clarify any issues or questions from
potential applicants is welcomed. Direct
inquiries regarding programmatic issues to your NCI program director. Direct inquiries regarding fiscal matters to
the NCI grants
management specialist responsible for the administration of
the grant. The names of these individuals can be found on the award statement
for the grant or may be obtained from the NCI Division of Cancer Biology,
telephone (301) 435-5226., e-mail: jk339o@nih.gov.
Authority
and Regulations
This
program is described in the Catalog of Federal Domestic Assistance Numbers
93.821, 93.859, and 93.862. Awards are made under authorization of the Public
Health Service Act, as amended 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.
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, a 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.
Division of
Cancer Biology
National
Cancer Institute
National
Institutes of Health
Bethesda,
Maryland 20892-6200
Last
updated: April 7, 2003