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
 (http://www.niddk.nih.gov)

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 
http://grants.nih.gov/grants/funding/phs398/phs398.html.

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 
(http://grants.nih.gov/grants/guide/pa-files/PAR-01-056.html). 
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 
http://www.health.gov/healthypeople/.

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 
(http://grants.nih.gov/grants/guide/pa-files/PAR-01-066.html) 
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 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); 
a complete copy of the updated Guidelines are available at  
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm:  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: http://grants.nih.gov/grants/guide/notice-files/not98-024.html

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: 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

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:
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm

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 http://grants.nih.gov/grants/funding/phs398/phs398.html are to be used in 
applying for these grants and will be accepted at the standard application 
deadlines (http://grants.nih.gov/grants/dates.htm) 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 301/435-0714, Email: GrantsInfo@nih.gov.

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 
http://grants.nih.gov/grants/funding/phs398/phs398.html 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 
http://grants.nih.gov/grants/funding/modular/modular.htm.  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:  fh14e@nih.gov 

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: mm102i@nih.gov

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: js362q@nih.gov

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:  sy29f@nih.gov 

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:  dh48v@nih.gov

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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