Novel approaches to enhance animal stem cell research.

The purpose of this program announcement (PA) is to encourage research to enhance animal stem cells as model biological systems. Innovative approaches to isolate, characterize, and identify totipotent and multipotent stem cells from nonhuman biomedical research animal models, as well as to generate reagents and techniques to characterize and separate those stem cells from other cell types, is encouraged. Embryonic and other stem cells are valuable biomedical research models for the study of biological and disease processes and the creation of disease models. In addition, these cells hold promise as model systems for development of therapeutics and of replacement tissues.

Thus far, embryonic stem cells have been isolated from some biomedically important nonhuman research models. In addition, stem cells with a more restricted potential have been characterized from post-embryonic tissue types. However, research is needed to provide fur a full array of totipotent and multipotent stem cells from nonhuman biomedical research animal models, as well as to provide the research tools to identify, characterize, and purify those cells.

This PA supports the isolation and characterization of embryonic and other multipotent stem cells in a variety of nonhuman animal species. Examples of research areas appropriate to this PA include, but are not limited to, projects to 1) expand the number of nonhuman animal model systems in which embryonic stem cells are available; 2) identify, isolate, culture, and characterize multipotent stem cell populations derived from nonhuman embryonic stem cells; 3) identify, isolate, culture, and characterize multipotent stem cells from postfetal tissue types; 4) generate and use panels of markers for stem cell attributes common across species for use in characterization and isolation of stem cells in a range of animal species or tissues; and 5) create universal methods of culture to maintain the undifferentiated state of embryonic or other characterized multipotential stem cells across nonhuman animal species.

Projects supported by the National Center for Research Resources under this PA are intended to generate research tools, reagents, or stem cells of utility to research on a broad range of tissue or cell types and of interest to more than one categorical or disease-oriented NIH institute or center. Projects that will focus on research on tissues or disease processes specific to the mission of an institute or center should be directed to the respective facility.

This PA will use the NIH R01 and R21 award mechanisms. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project. R21 applications should meet the requirements for this mechanism as recently redefined in PA-03-107, available at http://grants.nih.gov/grants/ guide/pa-files/PA-03-107.html. In brief, by using the R21 mechanism, the NIH seeks to foster the introduction of novel scientific ideas, model systems, tools, agents, targets, and technologies that have the potential to substantially advance biomedical research. These studies may involve considerable risk but may lead to breakthroughs, developments, or applications that could have a major impact on a field of biomedical, behavioral, or clinical research.

Applications for R21 awards should describe projects distinct from those supported through the traditional R01 mechanism. For example, long-term projects or projects designed to increase knowledge in a well-established area will not be considered for R21 awards. Applications submitted under this mechanism should be exploratory and novel. These studies should break new ground or extend previous discoveries toward new directions or applications.

Applications for R21 awards may request a project period of up to two years with a combined budget for direct costs of up to $275,000 for the two-year period. The request should be tailored to the needs of the project. Normally, no more than $200,000 may be requested in any single year.

This PA uses just-in-time concepts. It also uses the modular budgeting as well as the nonmodular budgeting formats (see http://grants.nih.gov/grants/funding/ modular/modular.htm). Specifically, if you are submitting an application with direct costs in each year of $250,000 or less, use the modular budgeting format. Otherwise, follow the instructions for nonmodular budgeting research grant applications. This program does not require cost sharing as defined in the current NIH Grants Policy Statement at http://grants.nih.gov/ grants/policy/nihgps_2003/NIHGPS_Part2.htm.

Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001). Applications must have a Duo and Bradstreet Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for federal grants or cooperative agreements. The DUNS number can be obtained by calling 1-866-705-5711 or through the website at http://www.dunandbradstreet.com/. The DUNS number should be entered on line 11 of the face page of the PHS 398 form. The PHS 398 document is available at http://grants.nih.gov/grants/ funding/phs398/phs398.html in an interactive format. For further assistance, contact GrantsInfo by calling 301-435-0714 or e-mailing [e-mail].

Applications submitted in response to this PA will be accepted at the standard application deadlines, which are available at http://grants.nih.gov/grants/ dates.htm. Application deadlines are also indicated in the PHS 398 application kit.

Contact: For the complete listing of contacts, please consult the full PA, available online at http://grants1.nih.gov/grants/guide/pa-files/ PA-04-125.html. Reference: PA No. PA-04-126