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Supplements for Functional Studies Based on High Resolution Structures Obtained in the Protein Structure Initiative

This announcement appears in the NIH Guide for Grants and Contracts as NOT-GM-08-123.

The supplements described in this notice are available only to investigators who (1) have NIGMS support and (2) wish to pursue research that is within the general scope of their parent NIGMS grant. Other investigators who do not meet both criteria and who wish to characterize the function of proteins from the Protein Structure Initiative (PSI) Centers should see the note following this announcement for information on collaborative funding that may be possible through the PSI Centers.

This announcement contains the following information:

Purpose of this Announcement

The National Institute of General Medical Sciences (NIGMS) announces the availability of administrative supplements to certain NIGMS grants. These supplements shall provide immediate support of short-term research projects which meet the following objectives: the research focuses on a protein of unassigned function that has been well-characterized structurally by one of the NIGMS-supported Protein Structure Initiative (PSI) Centers described below; the research seeks, through experimental approaches, to ascribe a biochemical function or cellular role to the protein; and the research is within the general scope of the parent NIGMS grant. The purpose of this supplemental grant program is to provide funds to enable investigators interested in protein function to capitalize on the information and material products of the PSI.

NIGMS currently supports fourteen research centers in the field of structural genomics. These research centers comprise a large-scale, high-throughput research network in protein structural genomics based on X-ray crystallography and NMR methods. The activities supported within the PSI centers include all of the constituent tasks of structural genomics including (1) protein family classification and target selection, (2) cloning and expression of proteins in suitable quantities, (3) preparation of samples for structural studies, (4) structure determination and (5) analyses and dissemination of results. The goal of these centers is to optimize and integrate all aspects of the structural genomics enterprise so that highly reliable protein structural information can be rapidly obtained. These centers pursue limited computational studies, based on sequence and structural homologies, to define functional possibilities; however, experimental work to elucidate the function of proteins selected for structure determination is not supported within these centers. (Information on these centers is available online.)

The activities of the PSI centers can be tracked using the web-based informatics tools, TargetDB (http://targetdb.pdb.org/), the protein expression, purification, and crystallization database PepcDB (http://pepcdb.rcsb.org/), the Knowledgebase portal (http://kb.psi-structuralgenomics.org/KB/index.jsp) and the Protein Data Bank (http://www.rcsb.org/pdb/). Investigators interested in protein function may consult these databases to learn not only what structures have been completed in these centers but also what proteins have been selected as targets for structure determination. Investigators may use the structure (and sequence) information in these databases to formulate experimental plans for investigating proteins with undetermined functions; they may also obtain certain resources from the PSI centers or the Materials Repository (http://www.hip.harvard.edu/PSIMR/index.htm) to facilitate the functional studies funded by these supplements.

Eligibility Requirements

A Principal Investigator having an active NIGMS research project grant to study protein function is eligible to apply for this supplement. The investigator should be interested in including in the project a protein that has been characterized structurally by one of the PSI centers. The investigator may want to contact scientists within the centers to obtain available materials (e.g., expression vectors and/or protein samples) as well as any background information associated with the protein in question; however, if other sources of the protein have been demonstrated and are assured, cooperation with a PSI center is not necessary. The intellectual initiative and experimental effort should come from the scientist studying the functional question. The parent NIGMS grant must have at least six months of support remaining at the time the supplement is awarded. Investigators interested in these supplements are strongly encouraged to contact NIGMS officials before applying.

Mechanism of Support

The awards will be made through administrative supplements to R01, R37, P01 and S06 awards. The supplemental funding must be for research activities that are within the general scope of the parent grant. Awards will be made in amounts up to $50,000 in direct costs for up to one year. As noted above, another funding mechanism is available for those investigators who do not have an appropriate NIGMS R01, R37, P01, or S06 award. 

Program Objectives

As the sequences of the human genome and a range of other organisms become available, sequence homology comparisons leave a remarkable fraction of open reading frames without assignable function. The targets for structure determination within the PSI centers are selected according to their relationship to recognizable protein families and generally without regard to their possible biological function. Thus, it is likely that a significant number of structures determined by the PSI during the present pilot phase and subsequently in the production phase will be without a functional assignment. It is the objective of this administrative supplement program to provide an efficient, cost-effective funding mechanism to facilitate and encourage the examination of the function of proteins for which structures have been obtained by one of the PSI centers. It is anticipated that the newly available structures, together with sequence information, will suggest hypotheses which can be promptly tested by well-designed functional studies. In some cases, studies of this type will provide suitable preliminary data to undergird NIH grant applications for support of new (and separately fundable) projects aimed at the detailed study of the function of particular proteins.

The impact of these administrative supplements will be in three areas: they will foster the use of the structural information and material resources that are emerging from the PSI centers; they will support research that should add to the significance of the structural information being developed; and they will foster new projects to elucidate the detailed functional characteristics of specific proteins.

Special Requirements

A progress report will be required as part of the non-competing application (type 5) or included in the final progress report as a part of the grant close-out process if there is no non-competing application.

Application Procedures

A request for a supplement may be made at any time. Applications received in the months of August and September may not be awarded until the next fiscal year. 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 NIGMS. The request is not to be submitted to the NIH Center for Scientific Review.

Requests for supplemental support must be submitted on the PHS 398, which is available on the World Wide Web at http://grants.nih.gov/grants/funding/phs398/phs398.html. Application kits are also available at most institutional offices of sponsored research.
The original and three copies of the request should be submitted to:

Ms. Grace Olascoaga
National Institute of General Medical Sciences
45 Center Drive MSC 6200
Bethesda, MD 20892-6200

The application should contain the face page, abstract page, and budget page. Justification for the budget should be submitted on a separate page (up to $50,000 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, is an important part of the review and award process and must be included in this application. Please use the Other Support page of the PHS 398 in providing this information. The proposal should be no longer than 10 pages, excluding the budget page and any supporting documents. Letters of commitment from any collaborators or consultants are among the supporting documents that should be submitted with the application.

The application should include a brief description of the project; background information and preliminary data, if any; plans for exploring the functional properties of the protein(s); and documentation that the principal investigator and collaborators have the requisite scientific expertise.

Review Considerations

Upon receipt, applications will be reviewed for completeness by NIGMS staff. Incomplete applications will be returned without review. Applications that are complete and responsive to the goals of the supplement announcement will be evaluated for scientific and technical merit through an NIGMS staff review, using outside experts (as needed), and applying the following general criteria:

  • scientific, biological, or medical significance of the proposed research;
  • appropriateness of the protein selected for study;
  • 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 significance and feasibility of the proposed research;
  • qualifications and research experience of the principal investigator (preference will be given to new investigators in their first competing segment) and of any collaborator;
  • other support available to the principal investigator and collaborator;
    availability of funds.

Inquiries

Inquiries are strongly encouraged. The opportunity to clarify any issues or questions from potential applicants is welcomed. Inquiries regarding programmatic issues should be directed to the program staff member associated with the existing NIGMS grant; inquiries regarding fiscal matters should be directed to the NIGMS 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 NIGMS Division of Extramural Activities; telephone (301) 594-5135. Inquiries may also be directed to Dr. Charles Edmonds, edmondsc@nigms.nih.gov or Dr. Ward Smith, smithwar@nigms.nih.gov.

Authority and Regulations

This program is described in the Catalog of Federal Domestic Assistance Number 93.859. 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.


Note on Collaborative Funding

For investigators not meeting all the requirements described in the above announcement of administrative supplements to NIGMS research grants for functional studies of PSI structures, support may be possible through the PSI research centers.  These investigators will fall into two categories: (1) those without an NIGMS grant and (2) those who have an NIGMS grant but who are contemplating functional studies which are not within the general scope of the project supported by that grant.  Funding for functional studies of PSI structures is available to qualified investigators in these situations via administrative supplements to PSI Centers.
 
The supplemental funds would be added to the grant for a PSI research center, but be made available via a subcontract to the functional study investigator at his or her institution.  The PSI research center would receive appropriate indirect cost funds for administering the subcontract, but participating members of the PSI Center would be ineligible for funding for investigations of protein function.
 
Investigators who wish to pursue this possibility should read the announcement concerning the administrative supplements and, after establishing the feasibility of a collaboration with a PSI Center, discuss the possibilities of such funding with Dr. Charles Edmonds (301-594-0828) or Dr. Ward Smith (301-443-9375). 
This page last updated November 19, 2008