RESEARCH ON SALIVARY GLANDS AND SECRETIONS

NIH GUIDE, Volume 22, Number 1, January 8, 1993



PA NUMBER:  PA-93-035



P.T. 34



Keywords:

  Oral Diseases 

  Clinical Medicine, General 



National Institute of Dental Research



PURPOSE



The National Institute of Dental Research (NIDR) supports studies to

improve knowledge of the development, structure, function, and

diseases of the salivary glands and to determine the influence of

salivary constituents on oral health.  Toward this end, the NIDR

seeks to enhance its support of basic and clinical research in the

broad area of the salivary system.



HEALTHY PEOPLE 2000



The Public Health Service (PHS) is committed to achieving the health

promotion and disease prevention objectives of "Healthy People 2000,"

a PHS-led national activity for setting priority areas.  This Program

Announcement (PA), Research on Salivary Glands and Secretions, is

related to the priority area of oral health.  Potential applicants

may obtain a copy of "Healthy People 2000" (Full Report:  Stock No.

017-001-00474-0) or "Healthy People 2000" (Summary Report:  Stock No.

017-001-00473-1) through the Superintendent of Documents, Government

Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238).



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.

Domestic applications may include international components.  Foreign

institutions are not eligible for the First Independent Research

Support and Transition (FIRST) (R29) award.  Applications from

minority individuals and women are encouraged.  Special eligibility

requirements specified in the pertinent guidelines for the various

mechanisms available for support of this program must be met.



MECHANISMS OF SUPPORT



The mechanisms available for support of this program include the

traditional research project grant (R01), the program project grant

(P01), the First Independent Research Support and Transition (FIRST)

(R29) award, and the small grant (R03).



Because the nature and scope of the research proposed in response to

this PA may vary, it is anticipated that the size of an award will

vary also.



RESEARCH OBJECTIVES



Background



Salivary gland research over the past two decades has been

compartmentalized into two general areas:  (1) salivary secretions

(extracellular events) and (2) salivary glands (intracellular

processes).  Our knowledge of salivary secretions has proceeded at a

faster pace than that of intracellular processes.  Nevertheless,

salivary research is at a crossroads due to the emergence of new

biologies, most notably recombinant technologies, cell biology, and

protein engineering.  Indeed, the future of salivary research will

require the integration of these new disciplines with the more

traditional disciplines.  Salivary researchers are at the critical

threshold of having a large volume of scientific information that can

be applied clinically towards enhancing natural defense mechanisms.

For example, studies in the not-too-distant future could be directed

toward topical vaccines against oral disease, the development of

artificial salivas, or the diagnostic use of sialochemistry by dental

practitioners.  Before these clinical goals can be achieved, however,

additional research is needed regarding the intracellular and

extracellular events that modulate saliva secretion and function.

Finally, clinical applications will demand consideration of normal

vs. the compromised host, normal vs. high-risk populations, and local

vs. systemic diseases in order to develop the appropriate diagnostic

and treatment modalities.



Research Goals and Scope



The NIDR has been a mainstay of support for research and related

training on salivary glands and their secretions and has thus

contributed to advances in basic research and furthered progress in

understanding diseases or syndromes in which salivary gland function

is compromised.  Based on recommendations by the Dental Research

Programs Advisory Committee at its June 7-8, 1988 meeting, the NIDR

"Broadening the Scope:  Long-Range Research Plan for the Nineties,"

and the NIDR-sponsored international conference on "Contemporary

Developments in Salivary Research" organized by Dr. Michael J. Levine

and held on November 6-10, 1991 at Buffalo, New York, the NIDR

desires to enhance its support of both basic and clinical research in

the broad area of this announcement.  Accordingly, applications are

invited for research project grants (including minority research

supplements), program project grants, FIRST awards, and small grants

related, but not limited to, the following areas:



o  Description of the characteristics of the salivary-associated

lymphoid tissue with emphasis on:  (a) the mechanisms of homing of

immune component cells to and within salivary glands, (b) the

cellular elements and factors regulating differentiation and antibody

production within specific gland types, including neuropeptide

modulation of salivary immunity, (c) the intrinsic and extrinsic

factors involved in the ontogeny of salivary immunity, and (d)

specific enhancement of host defenses using local antigen delivery

methods.



o  Definition of the molecular mechanisms involved in salivary

secretion with emphasis on: (a) the diversity of signal transduction

processes present in different salivary tissues and species, (b) the

mechanisms of sorting and packaging of stored proteins into secretory

granules in acinar cells, and (c) the mechanisms of secretory

granule-plasma membrane fusion and its role on the process of

exocytosis.



o  Further definition of the mechanisms of salivary-specific gene

expression in developing and adult glands of various species with

emphasis on:  (a) the trans-acting factors that modulate gene

transcription, and (b) the exogenous factors that modulate gene

expression, thereby enabling genetic manipulation of salivary glands

to address clinical problems.



o  Development of sophisticated model systems (transgenic animals and

immortalized salivary gland epithelial cell lines with appropriate

phenotypic expression) to investigate normal cellular processes and

those evident in disease.



o  Extension of studies of the structure and function of salivary

macromolecules to determine specific functional domains.



o  Confirmation of the biological role of individual salivary

molecules in vivo.



o  Definition of salivary function in acquired immune deficiency

syndrome (AIDS) and clarification of the role of salivary secretions

in preventing oral transmission of human immunodeficiency virus

(HIV).



o  Further research on the use of saliva to diagnose and monitor drug

therapy and abuse, endocrine function, systemic disease, oral health,

genetic defects, nutritional status, and age-specific changes.



o  Further investigations on the epidemiology, etiology,

pathogenesis, diagnosis, and treatment of salivary gland disorders,

such as Sjogren's syndrome.



o  Development of new sialogogues and improved, long-acting saliva

substitutes.



o  Development of methods to expand and improve function of residual

salivary gland tissue after destructive disease or therapy (e.g.,

radiation or chemotherapy to treat head and neck cancers).  This

research should include methods aimed at tissue repair and

regeneration.



o  Development of organoids and techniques for the preservation and

transplantation of salivary glands.



It should be reemphasized that the above list of potential areas of

investigation is not intended to be either comprehensive or

exclusive, nor is it in order of priority. Rather, it is intended to

exemplify the wide variety of new and/or continuing program emphases.



STUDY POPULATIONS



SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH

POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL

RESEARCH STUDY POPULATIONS



NIH policy is that applicants for NIH clinical research grants and

cooperative agreements are required to include minorities and women

in study populations so that research findings can be of benefit to

all persons at risk for the disease, disorder or condition under

study; special emphasis must be placed on the need for inclusion of

minorities and women in studies of diseases, disorders and conditions

which disproportionately affect them.  This policy is intended to

apply to males and females of all ages.  If women or minorities are

excluded or inadequately represented in clinical research,

particularly in proposed population-based studies, a clear compelling

rationale must be provided.



The composition of the proposed study population must be described in

terms of gender and racial/ethnic group.  In addition, gender and

racial/ethnic issues should be addressed in developing a research

design and sample size appropriate for the scientific objectives of

the study.  This information must be included in the form PHS 398

(rev. 9/91) in Sections 1-4 of the Research Plan AND summarized in

Section 5, Human Subjects.  Applicants are urged to assess carefully

the feasibility of including the broadest possible representation of

minority groups.  However, NIH recognizes that it may not be feasible

or appropriate in all research projects to include representation of

the full array of United States racial/ethnic minority populations

(i.e., Native Americans [including American Indians or Alaskan

Natives], Asian/Pacific Islanders, Blacks, Hispanics).  The rationale

for studies on single minority population groups should be provided.



For the purpose of this policy, clinical research is defined as human

biomedical and behavioral studies of etiology, epidemiology,

prevention (and preventive strategies), diagnosis, or treatment of

diseases, disorders or conditions, including but not limited to

clinical trials.



The usual NIH policies concerning research on human subjects also

apply.  Basic research or clinical studies in which human tissues

cannot be identified or linked to individuals are excluded.  However,

every effort should be made to include human tissues from women and

racial/ethnic minorities when it is important to apply the results of

the study broadly, and this should be addressed by applicants.



For foreign awards, the policy on inclusion of women applies fully;

since the definition of minority differs in other countries, the

applicant must discuss the relevance of research involving foreign

population groups to the United States' populations, including

minorities.



If the required information is not contained within the application,

the review will be deferred until the information is provided.



Peer reviewers will address specifically whether the research plan in

the application conforms to these policies.  If the representation of

women or minorities in a study design is inadequate to answer the

scientific question(s) addressed AND the justification for the

selected study population is inadequate, it will be considered a

scientific weakness or deficiency in the study design and will be

reflected in assigning the priority score to the application.



All applications for clinical research submitted to NIH are required

to address these policies.  NIH funding components will not award

grants or cooperative agreements that do not comply with these

policies.



APPLICATION PROCEDURES



Applications will be accepted in accordance with the receipt, Initial

Review Group, National Advisory Council, and earliest possible

beginning dates specified in the pertinent application kits.  The

specific application forms and kits required in this connection are

available at most institutional offices of sponsored research and may

be obtained from the Office of Grants Inquiries, Division of Research

Grants, National Institutes of Health, Westwood Building, Room 449,

Bethesda, MD 20892, telephone (301) 496-7441.  The YES box must be

checked and the title, Research on Salivary Glands and Secretions,

and number of the announcement must be typed in Section 2a on the

face page of the application form PHS 398 (rev. 9/91).



FIRST award applications must include at least three sealed letters

of reference attached to the face page of the original application.

FIRST award applications submitted without the required number of

reference letters will be considered incomplete and will be returned

without review.



The completed original application and five legible copies must be

sent or delivered to:



Division of Research Grants

National Institutes of Health

Westwood Building, Room 240

Bethesda, MD  20892**



REVIEW PROCEDURES



Applications will be assigned on the basis of established PHS

referral guidelines.  Applications will be reviewed for scientific

and technical merit in accordance with standard NIH peer review

procedures and the review criteria customary for the support

mechanism selected.  Following scientific-technical review, the

applications will receive a second-level review by one or more

appropriate national advisory councils or boards.



AWARD CRITERIA



Applications recommended for further consideration will compete for

available funds with all other applications.  The following will be

considered in making funding decisions:  quality of the proposed

project as determined by peer review, availability of funds, and

program balance among research areas of the announcement.  The NIDR

appreciates the value of complementary funding from other public and

private sources, including foundations and industrial concerns, for

activities that will complement and expand those supported by the

NIDR.



INQUIRIES



Written and telephone inquiries are encouraged.  The opportunity to

clarify any issues or questions from potential applicants is welcome.



Direct inquiries regarding programmatic issues to:



G.G. Roussos, Ph.D.

Director, Salivary Research and Oral Biology Centers Program

Extramural Program

National Institute of Dental Research

Westwood Building, Room 509

Bethesda, MD  20892

Telephone:  (301) 496-7784



Direct inquiries regarding fiscal matters to:



Ms. Theresa Ringler

Chief, Grants Management Section

Extramural Program

National Institute of Dental Research

Westwood Building, Room 510

Bethesda, MD  20892

Telephone:  (301) 496-7437



AUTHORITY AND REGULATIONS



This program is described in the Catalog of Federal Domestic

Assistance No. 93.121.  Awards are made under authorization of the

Public Health Service Act, Title IV, Part A (Public Law 78-410, as

amended by Public Law 99-158, 42 USC 241 and 285) 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.



.

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