This Program Announcement expires on September 1, 2004 unless reissued.

MECHANISMS IN NUTRITION AND INFECTION

Release Date:  August 29, 2001

PA NUMBER:  PA-01-133

National Institute of Dental and Craniofacial Research
National Institute of Allergy and Infectious Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
Office of Dietary Supplements

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 National Institute of Dental and Craniofacial Research (NIDCR), National 
Institute of Allergy and Infectious Diseases (NIAID), National Institute of 
Diabetes and Digestive and Kidney Diseases (NIDDK) and NIH Office of Dietary 
Supplements (ODS) invite grant applications to investigate basic, 
epidemiological and clinical research on nutrition (including dietary 
supplements) and infection.   The relationship between infection and nutrition 
is bi-directional in that infection can result in malnutrition, and 
malnutrition can contribute to infection.  Applicants are encouraged to 
assemble research expertise in the areas of nutrition, microbiology and 
immunology to explore these complex interrelationships between nutrition and 
infection.  Mechanistic studies aimed at understanding the molecular and 
cellular connections between nutrition and infections, immunity and 
inflammation are especially needed.  

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), 
Mechanisms in Nutrition and Infection, is related to the priority areas of 
Nutrition and Infectious Diseases.   Potential applicants may obtain a copy of 
"Healthy People 2010" at http://www.health.gov/healthypeople/.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign, 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.

MECHANISM OF SUPPORT

This PA will use the National Institutes of Health (NIH) research project 
grant (R01) award and the developmental grant (R21)award mechanisms.  
Responsibility for the planning, direction, and execution of the proposed 
project will be solely that of the applicant.  The total project period for an 
application submitted in response to this PA may not exceed five years for R01 
projects and two years for R21 projects.  R21 applications cannot exceed 
$100,000 in direct costs per year.  Applicants with budget requests that 
exceed $500,000 in direct costs in any year of the project should refer to the 
NIH policy on such applications:  
http://grants.nih.gov/grants/guide/notice-files/not98-030.html. 

Specific application instructions have been modified to reflect "MODULAR 
GRANT" and "JUST-IN-TIME" streamlining efforts that have been adopted by the 
NIH. Complete and detailed instructions and information on Modular Grant 
applications have been incorporated into the PHS 398 (rev. 5/2001).  
Additional information on Modular Grants can be found at 
http://grants.nih.gov/grants/funding/modular/modular.htm

R01s greater than $250,000 per year require detailed budgets and do not follow 
Modular Grant format.

RESEARCH OBJECTIVES

Background information

Globally, infectious diseases manifested either as acute or chronic illnesses 
are responsible for high morbidity and mortality. Epidemiological studies show 
that poor nutritional status can influence the incidence and the severity of 
infectious diseases. Other studies show a strong association between 
nutritional impairment and the development of chronic diseases with potential 
infectious etiologies such as cardiovascular diseases, cancer, and diabetes. 
However, there are still major gaps in our understanding of the 
interrelationships between nutrition and infection. For instance, very little 
is known about the mechanisms by which nutrition-related immunosuppression 
leads to increased susceptibility to infection. Clearly, this is a 
multifactorial issue and there are several interacting variables including 
host genetics, pathogen virulence, environmental factors, age, and gender. 
Moreover, the complexity of each independent variable makes it difficult to 
understand the underlying mechanisms. Thus, there is a need to address current 
concepts such as the role of nutrition on immunity and the related impact on 
infection and newer concepts such as the direct effects of nutrients on the 
genetic composition of microbes. It is expected that recent advances in 
molecular technology and the availability of human as well as several 
microbial genomes should enhance the progress in this area.

Because of the strong association between nutrient depletion and increased 
susceptibility to infection, national and international agencies have been 
very supportive of nutritional supplementation programs. However, a greater 
understanding of the cellular and molecular mechanisms involved will 
facilitate the optimal clinical use of nutrients in the reduction of the 
morbidity and mortality associated with infection. 

Recent workshops sponsored by the National Institutes of Health on nutrition 
and infectious diseases, nutrition and oral diseases and the effects of 
specific nutrients on immune-mediated diseases, which included participants 
with expertise in nutrition, immunology, molecular biology, and infectious 
disease, emphasized the need to continue to examine the potential mechanisms 
by which specific nutrients may contribute to poor clinical conditions.  

Summary

Research Objectives and scope

The intent of this program announcement is to advance our understanding of the 
cellular and molecular mechanisms involved in the relationships between 
nutrition and infection. It is anticipated that applicants will take advantage 
of the availability of new technologies and the availability of recent genomic 
data. Examples of research topics include, but are not limited to:

o Determination of the role of nutritional factors in microbial pathogenesis 
and host susceptibility to infection using appropriate animal model and in 
vitro systems. These studies should also include elucidation of the molecular 
regulatory mechanisms involved in the pathogenesis of infectious diseases 
within the context of nutrition;

o Examination of the interplay between microbial pathogens as well as between 
specific nutritional components on the pathogenesis of microbial infections;

o Examination of the impact of nutrition on the capacity of microbial 
pathogens to invade and grow in vascular and connective tissue;

o Examination of the role of inflammatory mediators in the pathogenesis of 
infectious diseases within the context of nutrition;

o Investigation of the potential mechanisms by which specific micronutrients 
interfere with the beneficial effects of other micronutrients during 
infection; 

o Examination of the direct effects of nutrients on pathogen virulence;

o Examination of the effects of dietary intervention with specific nutrients 
on the immune system; and,

o Examination of the link between nutritional status in early life and the 
development of infection later in adult life.

TERMS AND CONDITIONS OF AWARD

When clinical studies or trials are a component of the research proposed, 
studies must be monitored commensurate with the degree of potential risk to 
study subjects and the complexity of the study.  Terms and Conditions of Award 
will be included with awards.

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 subpopulations must be included in all NIH supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification is provided 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.

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.

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.

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.

Applications will be accepted at the standard application deadlines as 
indicated in the application kit. Application kits are available at most 
institutional offices of sponsored research and may be obtained from the 
Division of Extramural Outreach and Information Resources, National Institutes 
of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 
301/435-0714, email: GrantsInfo@nih.gov. In addition, the application kits can 
be found on the following URL: http://grants.nih.gov/grants/forms.htm.

Applicants planning to submit an investigator-initiated new (type 1), 
competing continuation (type 2), competing supplement, or any amended/revised 
version of the preceding grant application types requesting $500,000 or more 
in direct costs for any year are advised that he or she must contact the 
Institute program staff before submitting the application, i.e., as plans for 
the study are being developed. Furthermore, the application must obtain 
agreement from the program staff that the Institute will accept the 
application for consideration for award.  Finally, the applicant must 
identify, in a cover letter sent with the application, the staff member and 
Institute who agreed to accept assignment of the application.  This policy 
requires an applicant to obtain agreement for acceptance of any such 
application and any such subsequent amendment. Refer to the NIH Guide for 
Grants and Contracts, March 20, 1998 at 
http://grants.nih.gov/grants/guide/notice-files/not98-030.html

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 NIH 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:

Dennis Mangan, Ph.D.
Infectious Diseases and Immunity Branch
Division of Basic and Translational Sciences
National Institute of Dental and Craniofacial Research
Natcher Bldg, Room 4AN-32F
Bethesda, MD 20892-6402
Telephone: 301-594-2421
FAX: 301-480-8318
E-mail: Dennis.Mangan@nih.gov

Christopher E. Taylor, Sc.D.
Division of Microbiology & Infectious Diseases
National Institute of Allergy and Infectious Diseases
Room 3128, MSC-7630
6700-B Rockledge Drive
Bethesda, MD 20892-7630
Telephone: (301) 496-5305
FAX: (301) 496-8030
E-mail: ct18m@nih.gov

Michael K. May, Ph.D.
DDDN/NIDDK
6707 Democracy Blvd.
2 Democracy Plaza
Room 663, MSC 5450
Bethesda, MD 20892-5450 (For UPS & Fed EX use 20817)
Tel: 301-594-8884
Fax: 301-480-8300
E-mail: mm102i@nih.gov

Becky Costello, Ph.D.
Office of Dietary Supplements
National Institutes of Health
31 Center Drive,  Room 1B29
Bethesda, MD 20892-2086
phone: 301-435-2920
fax: 301-480-1845
email: CostellB@od.nih.gov

Direct inquiries regarding fiscal matters to:

Mr. William Powell
Grants Management Branch
National Institute of Dental and Craniofacial Research
Bg 45, Room 4AN-44A
Bethesda, MD 20892-6402
Telephone: 301-594-4800
FAX: 301-402-1517
E-mail: William.Powell@nih.gov

Ms Annette Hanapole
Grants Management Specialist
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2122, MSC-7614
6700-B Rockledge Drive
Bethesda, MD 20892-7614
Telephone: 301-402-5937
FAX: 301-480-3780
E-mail: ahanapole@niaid.nih.gov

Ms Desiree Johnson
Division of Extramural Activities
NIDDK
6707 Democracy Blvd.
2 Democracy Plaza
Room 713B, MSC 5456 
Bethesda, MD 20892-5456
Telephone: 301-594-8844
FAX: 301-480-3504
E-mail: JohnsonD@extra.niddk.nih.gov

AUTHORITY AND REGULATIONS 

This program is described in the Catalog of Federal Domestic Assistance No. 
93.121, Oral Diseases and Disorders Research Awards, 93.856, Microbiology and 
Infectious Diseases, and 93.847, 93.848, and 93.849, Diabetes and Digestive 
and Kidney Diseases. 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 Office of Dietary Supplements (ODS) was mandated by Congress in 1994 and 
established within the Office of the Director, National Institutes of Health 
(NIH). The Dietary Supplement Health and Education Act (DSHEA) [Public Law 
103-417, Section 3.a] amended the Federal Food, Drug, and Cosmetic Act “to 
establish standards with respect to dietary supplements.” This law authorized 
the establishment of the ODS.

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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