This Program Announcement expires October 1, 2004 unless reissued. INNOVATIVE AND EXPLORATORY RESEARCH IN DIGESTIVE DISEASES AND NUTRITION Release Date: August 20, 2001 PA NUMBER: PA-01-129 National Institute of Diabetes and Digestive and Kidney Diseases ( PURPOSE THIS PA USES "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. MODULAR INSTRUCTIONS MUST BE USED FOR RESEARCH GRANT APPLICATIONS UP TO $250,000 PER YEAR. MODULAR BUDGET INSTRUCTIONS ARE PROVIDED IN SECTION C OF THE PHS 398 (REVISION 5/2001) AVAILABLE AT PURPOSE The Division of Digestive Diseases and Nutrition at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) invites applications through the exploratory/developmental (R21) grant mechanism from investigators with research interests in gastroenterology, hepatology, obesity and nutrition and that serve the mission of NIDDK. The aim of this program announcement is to stimulate the application of highly novel approaches to important areas of digestive disease and nutrition research. This mechanism is primarily aimed at attracting and supporting new investigators in these research fields. Clinical or epidemiological research will not be supported through this Program announcement and should be submitted according to PAR-01-056 ( Applications will be accepted only from (1) newly independent investigators or (2) established investigators developing a completely new line of research. Results obtained from the R21 grant should allow subsequent submission of R01 applications focusing on research problems relevant to the study of digestive diseases and nutrition. These grants are not intended to support or supplement ongoing funded research of an established investigator, or to serve as an alternative mechanism of support for projects not receiving funding as competitive continuation applications. 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 Program Announcement (PA), Title of PA, is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as principal investigators. Furthermore, this mechanism is for the support of either new investigators [defined as independent investigators who have NOT yet held R01, R29, or subprojects of program project (P01) or center grants (P50) or equivalent], or established investigators entering a new research field or developing a completely new line of research. NIDDK K08 and K23 recipients, who are eligible for R03 grants ( are encouraged to utilize that mechanism of support. Receipt of a K-associated R03 does not preclude the subsequent submission of an application for this R21 program. MECHANISM OF SUPPORT This program will be supported through the exploratory/developmental grant (R21) mechanism. This provides short-duration support for preliminary studies of a highly speculative or innovative nature which are expected to yield, within the 2 year time frame, sufficient information upon which to base a well-planned and rigorously defined series of further investigations. Projects will be limited to $100,000 direct costs per year and are limited to two years duration. These grants will not be renewable, competing continuation applications will not be accepted. Continuation of projects developed under this program will be through the regular research grant mechanism (for example, R01). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The NIH Grants policy statement applies to these awards. Submission of an application under this PA precludes concurrent submission of any other Public Health Service application containing substantially the same research proposal. In addition, these R21 awards may not be used to supplement research projects currently supported by Federal or non-Federal funds, or to provide interim support of projects under review by the Public Health Service. RESEARCH OBJECTIVES Areas of special interest in this PA include but are not limited to: o Identification of novel signaling molecules and pathways involved in cellular and tissue development, differentiation, gene transcription, and function of the gastrointestinal tract, exocrine pancreas, liver and adipocytes. o Identification and characterization, isolation of gastrointestinal, pancreatic and hepatic stem cells. Identification and characterization the differentiation factors and processes determining gastrointestinal, pancreatic and adipose stem cells development into mature tissues and its potential uses as therapeutic alternatives. o Characterization of gastrointestinal neuroendocrine cell and enteric nervous system and their role in gastrointestinal motility and nutrient absorption. Nutrient-gene interaction and gene expression regulation. o Gastrointestinal, hepatic, and pancreatic cell regeneration and adaptive responses to to aging and injury mechanisms. The role of telomers and telomerase activity in tissue regeneration, dysplasia and aging in the setting of chronic injury and carcinogenesis. o Development, characterization and utilization of novel cellular and animal models of gastrointestinal, pancreatic and hepatic diseases. o Development of biological markers for staging and prognosis in diseases such us celiac disease, pancreatitis, colitis, immune and viral hepatitis, obesity and nonalcoholic steatohepatitis (NASH). o Development of novel vectors and delivery systems for use in gene therapy of gastrointestinal, pancreatic, hepatobiliary and nutritional diseases. o Development of new methods for temporal and spatial control of transgene expression in gastrointestinal, pancreatic, hepatic and adipose tissues/cells. High output characterization of gene expression and function from parenchymal and epithelial cells under physiological and pathological conditions, using microarrays, proteomics, RNA interference, differential display reverse transcriptase-polymerase chain reaction. o Identification of genes involved in susceptibility, phenotypic variation or response to therapy of gastrointestinal, hepatobiliary and pancreatic diseases or animal models of these diseases. o Development of animal and in vitro cellular models and test systems to investigate the mechanisms of drug-induced liver disease and explore innovative preventive and therapeutic interventions (replenishment of GSH or chaperon molecules) during acute episodes, or as preventive measures in situation of high hepatotoxic potential (chemotherapies)or prior to liver collection of transplant. o Development of novel non invasive imaging methods to study function of the gastrointestinal tract, liver, pancreas and adipose tissue and pathogenic processes such as fibrosis, inflammation, hyperplasia, fat body accumulation. o Elucidation of the pathogenesis of digestive and nutritional diseases of unknown or poorly defined cause, such as celiac disease, ulcerative colitis, Crohn’s disease, childhood motility disorders, functional bowel disease, chronic idiopathic pancreatitis, primary biliary cirrhosis, sclerosing cholangitis, autoimmune hepatitis, biliary atresia and childhood cholestatic liver diseases. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification are provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing research involving human subjects should read the UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research," published in the NIH Guide for Grants and Contracts on August 2, 2000 (, a complete copy of the updated Guidelines are available at The revisions relate to NIH defined Phase III clinical trials and require: a) all applications or proposals and/or protocols to provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable, and b) all investigators to report accrual, and to conduct and report analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of NIH that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. This policy applies to all initial (Type 1) applications submitted for receipt dates after October 1, 1998. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects" that was published in the NIH Guide for Grants and Contracts, March 6, 1998, and is available at the following URL address: Investigators also may obtain copies of these policies from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. 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. Reviewers are cautioned that their anonymity may be compromised when they directly access an Internet site. REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS NIH policy requires education on the protection of human subject participants for all investigators submitting NIH proposals for research involving human subjects. This policy announcement is found in the NIH Guide for Grants and Contracts Announcement dated June 5, 2000, at the following website: 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: Applicants may wish to place data collected under this PA 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. APPLICATION PROCEDURES The PHS 398 research grant application instructions and forms (rev. 5/2001) at are to be used in applying for these grants and will be accepted at the standard application deadlines ( as indicated in the application kit. This version of the PHS 398 is available in an interactive, searchable PDF format. Although applicants are encouraged to begin using the 5/2001 revision of the PHS 398 as soon as possible, the NIH will continue to accept applications prepared using the 4/1998 revision until January 9, 2002. Beginning January 10, 2002, however, the NIH will return applications that are not submitted on the 5/2001 version. For further assistance contact GrantsInfo, Telephone 301/710-0267, Email: All application instructions outlined in the PHS 398 application kit are to be followed, with the following modifications: 1. Applicants MUST cite the Program Announcement number on line 2 of the application. Applicants are strongly urged to contact the Program Directors listed in the INQUIRIES section prior to submission of a application, for advice about eligibility and responsiveness. 2. R21 applications will use the MODULAR GRANT and JUST-IN-TIME concepts, with direct costs requested in $25,000 modules, up to the total direct costs limit of $100,000 per year. 3. Although preliminary data are not required for an R21 application, they may be included. 4. Sections a-d of the Research Plan may not exceed 15 pages, including tables and figures. 5. Appendix materials should be limited, as is consistent with the exploratory nature of the R21 mechanism, and should not be used to circumvent the page limit for the research plan. Copies of appendix material will only be provided to the primary reviewers of the application and will not be reproduced for wider distribution. The following materials may be included in the appendix: o Up to five publications, including manuscripts (submitted or accepted for publication), abstracts, patents, or other printed materials directly relevant to the project. These may be stapled as sets. o Surveys, questionnaires, data collection instruments, and clinical protocols. These may be stapled as sets. o Original glossy photographs or color images of gels, micrographs, etc., provided that a photocopy (may be reduced in size) is also included within the 15 page limit of items a-d of the research plan. Include five collated sets of all appendix material, in the same package with the application, following all copies of the application. Identify each item with the name of the principal investigator. SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS The modular grant concept establishes specific modules in which direct costs may be requested as well as a maximum level for requested budgets. Only limited budgetary information is required under this approach. The just-in-time concept allows applicants to submit certain information only when there is a possibility for an award. It is anticipated that these changes will reduce the administrative burden for the applicants, reviewers and NIH staff. The research grant application form PHS 398 (rev. 5/2001) at is to be used in applying for these grants, with modular budget instructions provided in Section C of the application instructions. Applicants are permitted, however, to use the 4/1998 revision of the PHS 398 for scheduled application receipt dates until January 9, 2002. If you are preparing an application using the 4/1998 version, please refer to the step-by-step instructions for Modular Grants available at Additional information about Modular Grants is also available on this site. The title and number of the program announcement must be typed on line 2 of the face page of the application form and the YES box must be marked. Submit a signed, typewritten original of the application, including the Checklist, and five signed photocopies 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) REVIEW CONSIDERATIONS Applications will be assigned on the basis of established PHS referral guidelines. Applications will be evaluated for scientific and technical merit by an appropriate scientific review group convened in accordance with the standard NIH peer review procedures. As part of the initial merit review, all applications will receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed, assigned a priority score, and receive a second level review by the appropriate national advisory council or board. 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 the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that the 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, an investigator 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 this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? (2) Approach: Are the conceptual framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? (3) Innovation: Does the project employ novel concepts, approaches or method? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? (4) Investigator: Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)? (5) Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? In addition to the above criteria, in accordance with NIH policy, all applications will also be reviewed with respect to the following: o The adequacy of plans to include both genders, minorities and their subgroups, and children as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. o The reasonableness of the proposed budget and duration in relation to the proposed research o 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. AWARD CRITERIA Award 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. INQUIRIES Inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Frank Hamilton, M.D., M.P.H. Branch Chief Gastrointestinal Motility Program Director, Gastrointestinal Mucosa and Immunology Program Director, AIDS Program Director Division of Digestive Diseases and Nutrition National Institute of Diabetes and Digestive and Kidney Diseases Two Democracy Plaza, Room 627 6707 Democracy Boulevard Bethesda, MD 20892-5458 Telephone: (301) 594-8877 Fax: (301) 480-8300 Email: Michael Ken May, Ph.D. Gastrointestinal Neuroendocrinology Program Director, Gastrointestinal Transport and Absorption Program Director Division of Digestive Diseases and Nutrition National Institute of Diabetes and Digestive and Kidney Diseases Two Democracy Plaza, Room 627 6707 Democracy Boulevard Bethesda, MD 20892-5458 Telephone: (301) 594-8884 Fax: (301) 480-8300 Email: Jose Serrano M.D., Ph.D. Director Liver and Pancreas Programs Division of Digestive Diseases and Nutrition National Institute of Diabetes and Digestive and Kidney Diseases Two Democracy Plaza, Room 627 6707 Democracy Boulevard Bethesda, MD 20892-5458 Telephone: (301) 594-8871 Fax: (301) 480-8300 Email: Susan Yanovski M.D. Obesity and Eating Disorders Program, National Task Force on the Prevention and Treatment of Obesity Division of Digestive Diseases and Nutrition National Institute of Diabetes and Digestive and Kidney Diseases Two Democracy Plaza, Room 627 6707 Democracy Boulevard Bethesda, MD 20892-5458 Telephone: (301) 594-8882 Fax: (301) 480-8300 Email: Direct inquiries regarding fiscal and administrative matters to: Donna A. Huggins Division of Extramural Activities Grants Management Branch National Institute of Diabetes and Digestive and Kidney Diseases 2 Democracy Plaza Room 711 6707 Democracy Blvd Bethesda, MD 20892-5458 Telephone: (301) 594-8848 FAX: (301) 480-3504 Email: AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.849. 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 and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. 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, and 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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