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New opportunities for Structural Biology Studies Announced

 

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New opportunities for Structural Biology Studies Announced


Supplements for the Determination of High-Resolution Structures

           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

 

 

 

 

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