Subject: (Copy) NIH Guide Vol. 18, No. 34, September 29, 1989, Part 1 (final
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Mon, 02 Oct 89 08:19 EST

Paul,
   Please post as NIHGUIDE.092989.  Thanks
        Dottie
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Subject: NIH Guide Vol. 18, No. 34, September 29, 1989, Part 1 (final, RFAs foll

     

     
     
Vol. 18, No. 34, September 29, 1989

                                   NOTICES

AFFIRMATIVE ACTION, EQUAL OPPORTUNITY AND CIVIL RIGHTS POLICY
STATEMENT FOR CONTRACTORS AND GRANTEES .....................(84/157)......... 1
National Institutes of Health
Alcohol, Drug Abuse, and Mental Health Administration
Index:  NATIONAL INSTITUTES OF HEALTH
        ALCOHOL, DRUG ABUSE, AND MENTAL HEALTH ADMINISTRATION

                     DATED ANNOUNCEMENTS (RFPs AND RFAs)

CLINICAL EVALUATION OF FRUIT AND VEGETABLE BASED EXPERIMENTAL
FOOD SUPPLEMENTS (RFP) .....................................(164/213)........ 2
National Cancer Institute
Index:  CANCER

METHODS DEVELOPMENT FOR PHYTOCHEMICAL COMPLIANCE MARKERS IN
DESIGNER FOODS (RFP) .......................................(216/264)........ 2
National Cancer Institute
Index:  CANCER

SPECIAL STUDIES FACILITATING THE FLOW OF PRECLINICAL LEADS INTO
CLINICAL PRACTICE (RFP) ....................................(267/315)........ 3
National Cancer Institute
Index:  CANCER

IMMUNE RESPONSE TO XENOBIOTICS (RFP) .......................(321/363)........ 4
National Institute of Environmental Health Sciences
Index:  ENVIRONMENTAL HEALTH SCIENCES

POSTPRANDIAL LIPOPROTEINS AND ATHEROSCLEROSIS (RFA) ...(366/415, 804/1499)... 4
National Heart, Lung, and Blood Institute
Index:  HEART, LUNG, BLOOD

                        ONGOING PROGRAM ANNOUNCEMENTS

THE EFFECTS OF ORAL FACTORS ON TASTE AND SMELL ............(421/604)......... 5
National Institute of Dental Research
Index:  DENTAL

NASAL CHEMORECEPTION:  REGENERATION AND TROPHIC INTERACTIONS ..(607/757)..... 7
National Institute on Deafness and Other Communication Disorders
Index:  DEAFNESS, COMMUNICATION DISORDERS

     

     

     

     

     

     
                                   NOTICES

AFFIRMATIVE ACTION, EQUAL OPPORTUNITY AND CIVIL RIGHTS
POLICY STATEMENT FOR CONTRACTORS AND GRANTEES
     
P.T. 34; K.W. 1014006
     
National Institutes of Health
Alcohol, Drug Abuse, and Mental Health Administration
     
The National Institutes of Health (NIH) is the principal biomedical research
agency in the world.  Its mission is to provide leadership and direction to
biomedical research programs designed to improve the health of the American
people.  The NIH and the Alcohol, Drug Abuse, and Mental Health Administration
(ADAMHA) conduct and support research and research training on the causes,
diagnosis, prevention, and cure of human diseases, and on the fundamental
biological processes of human growth and development, and the biological
effects of the environment; supports programs for the collection,
dissemination, and exchange of information on medicine and health.
     
To accomplish this mission, the NIH funds over 500 contractors and over 1,300
grantee institutions to conduct biomedical research.  The NIH/ADAMHA also
employs consultants to advise on scientific and nonscientific programmatic
endeavors.  The NIH's/ADAMHA's effectiveness is dependent on the constructive
use of human resources.
     
Interwoven into the NIH/ADAMHA mission is a commitment to apply the principles
and concepts of affirmative action, equal opportunity, and civil rights.
NIH/ADAMHA decisions regarding employment, advancement, career development,
training, and the awarding of Federal funds are made and there should not be
any discrimination based on race, color, religion, national origin, gender,
age, handicap (both physical and mental), and Veterans and Veterans of the
Vietnam Era. The environment in which our contractors and grantees carry out
their daily functions must be free of discrimination.
     
It is to this end that a reaffirmation of our commitment to affirmative
action, equal opportunity, and civil rights is necessary.  NIH/ADAMHA
managers, supervisors, contracting and grants staff, contractors and grantees
are expected to ensure, with renewed vigor, that Equal Employment Opportunity
(EEO) principles are fully integrated into all aspects of NIH/ADAMHA
extramural and intramural programs and activities.  This commitment should
include, but not be limited to:
     
 o  increasing opportunities for the employment, training,
    and advancement of racial and ethnic minorities, women,
    handicapped individuals and disabled veterans;
 o  expanding grant and contract opportunities for minority
    institutions and contract opportunities for small,
    female-owned and disadvantaged businesses;
 o  increasing the number of minority and women faculty
    members in the research programs;
 o  increasing the participation of minorities, women,
    disabled persons, and Vietnam Era veterans on
    scientific review and public advisory committees; and
 o  ensuring that facilities are accessible and that
    reasonable accommodations are provided for disabled
    persons.
     
The number of minority and women-owned companies who have contracts with
NIH/ADAMHA has increased.  The number of grants that are awarded to minority
institutions has also increased.  The NIH/ADAMHA intends to integrate fully
these populations into our contracts and grants programs.
     
NIH/ADAMHA is committed to administrative and scientific excellence in our
research programs.  NIH/ADAMHA asks your cooperation with the Division of
Contracts and Grants, Contract Compliance Office to carry out both the spirit,
and intent of affirmative action, EEO, and civil rights laws.
     
All questions should be directed to:
     
Ms. Maureen B.E. Miles
Division of Contracts and Grants
Building 31, Room 1B-23
National Institutes of Health
Bethesda, Maryland  20892
Telephone:  (301) 496-2973

                 Vol. 18, No. 34, September 29, 1989 - Page 1
                     DATED ANNOUNCEMENTS (RFPs AND RFAs)

CLINICAL EVALUATION OF FRUIT AND VEGETABLE BASED EXPERIMENTAL FOOD SUPPLEMENTS
     
MASTER AGREEMENT RFP AVAILABLE:  NCI-CN-95198-69
     
P.T. 34; K.W. 0710095, 0202001, 0750025
     
National Cancer Institute
     
The National Cancer Institute (NCI), Prevention and Control Contracts Section,
is issuing a Request for Proposal (RFP) for Master Agreements to provide
Clinical Evaluation of Fruit and Vegetable Based Experimental Food Supplements
in the following areas:
     
TASK I - Dietary Modulation of Human Drug Metabolism by Phytochemical
Constituents in Fruits and Vegetables:  Requires conduct of acute human
metabolism studies on healthy people who are chronically consuming
experimental diets fortified with fruit and vegetable phytochemicals; cold
storage of blood, saliva, urine, etc., collected from study participants; and
split-sample analyses of experimental foods.
     
TASK II - Dietary Modulation of Arachidonic Acid Metabolism by Phytochemical
Constituents in Fruit and Vegetables.  Requires conduct of human studies
focused on measuring the modulatory influence of fruit and vegetable
phytochemicals on circulating prostagladin levels and arachidonic acid
metabolites in biological fluids.
     
TASK III - Dietary Modulation of Endogenous Steriod Metabolism by
Phytochemical Constituents in Fruits and Vegetables.
     
Offerors can submit proposals for either or all of the above tasks.  Each task
will be evaluated separately; however, and one pool of Master Agreement
Holders will be awarded.  All Master Agreement Holders will be able to compete
for Master Agreement Orders issued during a five-year period of performance.
     
It is estimated that up to two (2) Master Agreement Orders will be awarded for
each task area per year.  The Master Agreement Announcement will be available
on or about October 10, 1989.  Responses will be due on approximately December
20, 1989.
     
Copies of RFP No. NCI-CN-95198-69 may be obtained by sending a written request
to:
     
Mr. Vernon Rainey, Contracting Officer
National Institutes of Health
National Cancer Institute
Research Contracts Branch, PCCS
Executive Plaza South, Room 635
9000 Rockville Pike
Bethesda, Maryland  20892
Telephone:  (301) 496-8603

METHODS DEVELOPMENT FOR PHYTOCHEMICAL COMPLIANCE MARKERS IN DESIGNER FOODS
     
MASTER AGREEMENT RFP AVAILABLE:  NCI-CN-95199-69
     
P.T. 34; K.W. 0710095, 0202001, 0750025, 0755015, 0755018
     
National Cancer Institute
     
The National Cancer Institute (NCI), Prevention and Control Contracts Section,
is issuing a Request for Proposal (RFP) for Master Agreements to provide
Methods Development for Phytochemical Compliance Markers in Designer Food in
the following task areas:
     
TASK I - Provide analysis of Phytochemical Compliance Markers in Experimental
Foods including shelf-life stability studies, identifying sources for food
material, validating analytical methodology and participating in split-sample
analysis, etc.
     
TASK II - Provide analysis of Phytochemical Compliance Markers in Human
Biological Fluids.  This requires the accrual of 25 healthy individuals for
the study and verification of compliance markers in experimental foods and for
the determination of compliance markers in biological fluids of humans

                 Vol. 18, No. 34, September 29, 1989 - Page 2
consuming experimental foods.  Assist the National Cancer Institute in filing
of an IND with the FDA.
     
Offerors can submit proposals for either or both of the above tasks.  Each
task will be evaluated separately; however, one pool of Master Agreement
Holders will be awarded.  All Master Agreement Holders will be able to compete
for Master Agreement Orders issued during the five-year period of performance.
     
It is estimated that up to five (5) Master Agreement Orders will be awarded
for Task I, per year, and three (3) Master Agreement Orders for Task II, per
year.  The Master Agreement Announcement will be available on or about October
10, 1989.  Responses will be due on approximately December 20, 1989.
     
Copies of RFP No. NCI-CN-95199-69 may be obtained by sending a written request
to:
     
Mr. Vernon Rainey, Contracting Officer
National Institutes of Health
National Cancer Institute
Research Contracts Branch, PCCS
Executive Plaza South, Room 635
9000 Rockville Pike
Bethesda, Maryland  20892
Telephone:  (301) 496-8603

SPECIAL STUDIES FACILITATING THE FLOW OF PRECLINICAL LEADS INTO CLINICAL
PRACTICE
     
MASTER AGREEMENT RFP AVAILABLE:  NCI-CN- 95201-69
     
P.T. 34; K.W. 0710095, 0710040, 0755010, 0765025, 0760025
     
National Cancer Institute
     
The National Cancer Institute (NCI), Prevention and Control Contracts Section,
is issuing a Request for Proposal (RFP) for Master Agreements to provide
Special Studies Facilitating the Flow of Preclinical Research Leads into
Clinical Practice in the following task areas:
     
TASK I - Evaluation of Lipids and Lipoprotein in Fluids and Tissues of
Laboratory Animals Consuming Fruit and Vegetable Products.
     
TASK II - Evaluation of Antiestrogenic Activity Hormone Receptor Function and
Steriod Hormone Levels and Metabolism in Laboratory Animals Consuming Fruit
and Vegetable Products.
     
TASK III - Modulation of Arochidonic Acid Metabolism by Fruit and Vegetable
Products.
     
TASK IV - Evaluation of Modulatory Activity of Fruit and Vegetable Products on
Key Regulatory Enzymes, Antioxidant Defenses, and Cyclic Nucleotide Levels in
Laboratory Animals.
     
Offerors can submit proposals for either or all of the above tasks.  Each task
will be evaluated separately; however, and one pool of Master Agreement
Holders will be awarded.  All Master Agreement Holders will be able to compete
for Master Agreement Orders issued during a five-year period of performance.
     
It is estimated that approximately two to four Master Agreement Orders will be
awarded for each task area per year.  The Master Agreement Announcement will
be available on or about October 10, 1989.  Responses will be due on
approximately December 20, 1989.
     
Copies of RFP No. NCI-CN-95201-69 may be obtained by sending a written request
to:
     
Mr. Vernon Rainey, Contracting Officer
National Institutes of Health
National Cancer Institute
Research Contracts Branch, PCCS
Executive Plaza South, Room 635
9000 Rockville Pike
Bethesda, Maryland  20892
Telephone:  (301) 496-8603

     
     
                 Vol. 18, No. 34, September 29, 1989 - Page 3
IMMUNE RESPONSE TO XENOBIOTICS
     
RFP AVAILABLE:  NIH-ES-89-31
     
P.T. 34; K.W. 1007009, 0710070, 0715110
     
National Institute of Environmental Health Sciences
     
The National Institute of Environmental Health Sciences (NIEHS), National
Institutes of Health (NIH), is soliciting proposals for a project involving
immunotoxicity studies, including hypersensitivity, on various xenobiotics.
These studies will further the understanding of the potential toxicological
manifestations associated with the use of these compounds.  The project is
task oriented.  In year 1, the contractor will be required to demonstrate
proficiency in the uses of the immune testing panels using one known chemical.
If approved by the Project Officer, the contractor will be required to
initiate Task II which includes the following subtasks:  I-A - Dose Range
Finding studies on 4 xenobiotics; I-B - Immune Function Testing on 3
xenobiotics; I-C - Host Resistance Assays on 2 xenobiotics; and I-D - Mouse
Skin Hypersensitivity studies on 3 xenobiotics.  Those xenobiotics selected
for testing under subtasks I-A through I-C will overlap, while those selected
for testing in subtask I-D will probably be distinct.  In years 2-5, the
contractor will be required to continue Task II.  Specifically, the following
subtasks will be required each year:  II-A - Dose Range Finding studies on 6
xenobiotics; II-B - Immune Function Testing on 4 of the xenobiotics examined
under II-A; II-C - Host Resistance Assays on 2 of the xenobiotics examined in
II-B; and II-D - Mouse Skin Hypersensitivity testing on 4 chemicals.  In
addition, in years 2-5, Task III will be undertaken and will involve
development and implementation of new methodology.  The Government estimates
that this project will require approximately 2.2 professional person-years,
1.0 senior technical person-years, and 2.2 technical person-years per contract
year.  One contract is contemplated.  The RFP will be released on or about
October 4, 1989, with responses due by November 17, 1989.  All responsible
sources may submit a proposal which will be considered by the Agency.
     
Requests should reference RFP NIH-ES-89-31 and should be forwarded to:
     
National Institute of Environmental Health Sciences
Contracts and Procurement Management Branch, OM
ATTN:  Mary B. Armstead, Contracting Officer
79 T.W. Alexander Drive, 4401 Building
P.O. Box 12874
Research Triangle Park, North Carolina  27709

POSTPRANDIAL LIPOPROTEINS AND ATHEROSCLEROSIS
     
RFA AVAILABLE:  89-HL-15-P
     
P.T. 34; K.W. 0715040, 0765025, 0765032, 0785055
     
National Heart, Lung, and Blood Institute
     
Application Receipt Date:  January 16, 1990
     
The Social and Environmental Epidemiology Branch of the Division of
Epidemiology and Clinical Applications, National Heart, Lung, and Blood
Institute (NHLBI), announces the availability of a Request for Cooperative
Agreement Applications (RFA) for investigators to participate, with assistance
of NHLBI staff, in a multicenter study of the above subject.
     
Lipoproteins appearing in blood after a fatty meal may be particularly
atherogenic, contributing to disease development even in persons without
elevated fasting lipids.  This program will support collaborative planning and
conduct of a study to evaluate lipoprotein responses to an oral fat challenge
among persons with evidence of atherosclerosis (cases) and comparable
controls.  Results are intended to apply to atherosclerosis typically found in
general populations.  Some study elements will be performed following a common
protocol; others may differ at each study center.
     
This RFA may be of interest to investigators in several fields.
Multidisciplinary research is sought, requiring cooperation of persons with
biochemical and epidemiological expertise, and access to both an expert lipid
laboratory and a screened or examined population from which representative
cases and comparable controls are drawn.  Lipid measurements that are needed
are relatively complex.  Expertise in evaluating persons for evidence of
atherosclerotic disease is needed.

                 Vol. 18, No. 34, September 29, 1989 - Page 4
Inclusion of women and minority populations is encouraged; and if they are
excluded, reasons for their exclusion must be provided in the application.
     
Minority institutions are encouraged to apply, and other institutions are
encouraged to establish collaborative arrangements with minority institutions.
     
Interested parties may request a copy of the complete RFA from:
     
A. Richey Sharrett M.D., Dr.P.H.
Social and Environmental Epidemiology Branch
Division of Epidemiology and Clinical Applications
National Heart, Lung, and Blood Institute
Federal Building, Room 2C08
7550 Wisconsin Ave.
Bethesda, Maryland  20897

                        ONGOING PROGRAM ANNOUNCEMENTS

THE EFFECTS OF ORAL FACTORS ON TASTE AND SMELL
     
P.T. 34; K.W. 0715148, 1002034, 0745010, 0745020
     
National Institute of Dental Research
     
The Craniofacial Anomalies, Pain Control and Behavioral Research Branch of the
National Institute of Dental Research (NIDR) encourages submission of grant
applications to conduct research increasing understanding of relationships
between the chemical senses and the oral environment.  Of special interest are
studies identifying the impact of oral conditions/diseases, oral behaviors, or
dental procedures upon chemosensory function.  Studies clarifying processes
through which conditions in the oral environment influence taste and smell are
of particular interest.  Also encouraged are dentally-relevant studies
developing improved approaches to prevention, detection, diagnosis, or
treatment of impaired chemosensory functioning.  Through this announcement,
NIDR seeks to expand chemosensory research and to complement ongoing programs
of major support for research on taste and smell provided by the Division of
Communicative and Neurosensory Disorders in the National Institute of Deafness
and Other Communication Disorders (NIDCD).
     
BACKGROUND
     
The chemical senses of taste and smell involve chemical transduction of
molecules at olfactory and taste receptor sites.  These receptor cells show a
unique, and still poorly understood capability to replace themselves,
regenerating frequently as long as they are innervated.  Disorders of the
chemical senses impair quality of life and health through affecting vital
behaviors such as food intake and selection, or recognition of dangers (e.g.,
from spoiled food, gas leaks, etc.).
     
Though the exact prevalence of taste and smell disorders in the U.S.
population is not known, experience from NIH-sponsored regional clinical
centers studies suggests that well over 2 million U.S. adults suffer from
these conditions.  A recent survey involving 1.5 million participants
indicated that 1.2 percent suffered total loss of olfactory function.
Problems in chemosensation particularly afflict individuals over the age of
60--the most rapidly growing age group in the U.S. Olfactory abilities decline
progressively from early adulthood and substantial decrements are common among
older adults.  More subtle decrements in taste function (often associated with
illnesses or medical treatments rather than the aging process per se) also
occur.
     
Chemosensory impairments are found in systemic diseases such as multiple
sclerosis, diabetes, and Alzheimer's disease.  They can also result from head
injuries, colds or viral infections, cystic fibrosis, Sjogren's syndrome,
allergies, certain drugs, and chemotherapy and radiation treatment for
cancers.  Tase disorders may also accompany oral diseases, such as periodontal
diseases, xerostomia, or "burning mouth" syndrome.  Olfactory disorders often
result from obstruction of the nasal airway which occurs with nasal polyps or
some craniofacial anomalies.  The release of blood and infection byproducts
into the oral cavity from infections or disease can produce dysgeusias ("bad"
tastes) often not recognized to reflect oral pathology.  Conditions in the
oral cavity, such as altered salivary flow and composition, have been found to
influence taste function or produce dysgeusias.
     
Dentists are often the first health professionals consulted when patients
experience problems related to taste or smell.  Yet the available knowledge
     
                 Vol. 18, No. 34, September 29, 1989 - Page 5
base provides little information regarding the role of the oral environment in
chemosensation and minimal guidance for dental professionals concerning
effective prevention, detection, or treatment of chemosensory disorders.
     
RESEARCH GOALS
     
The NIDR seeks to expand understanding of mechanisms underlying relationships
between oral diseases or conditions and chemosensation; increase understanding
of relationships between various dental treatments and/or oral behaviors and
chemosensory function or dysfunction; improve the detection, prevention,
diagnosis, and treatment of chemosensory disorders in relation to the oral
environment or to oral health.
     
Basic, clinical, or epidemiological studies can be supported.  However,
responses to this announcement must relate to the above aims and/or show clear
ties to the oral environment, dental research approaches, oral health, or
dental care.
     
Basic studies might, for example, characterize mechanisms through which
aspects of the oral environment (e.g., salivary flow, oral pathology,
craniofacial injuries or craniofacial anomalies) modify chemosensory function.
Studies of age-related changes in oral tissues related to variations in taste
and olfaction are encouraged, as are studies assessing changes in chemosensory
function associated with dental procedures such as, use of dental prostheses
or dental implants, orthognathic surgery, or with oral habits (e.g., use of
smokeless or smoked tobacco).  Population-based or clinic-based
epidemiological studies may include, but are not limited to, studies
determining the prevalence of chemosensory disorders and related oral
disorders or studies of factors influencing individuals with chemosensory
disturbances to seek treatment.  It is anticipated that basic research may
receive greater emphasis initially, in order to establish an appropriate
context for structuring clinical research hypotheses and approaches.  Clinical
studies related to prevention, detection, diagnosis, or treatment of
chemosensory disorders may also be initiated, as relationships between oral
factors and oral sensory function become more clearly established.
     
MECHANISM OF SUPPORT
     
Support for this program will be provided through research or research
training grants, including regular project grants (R01), small grants (R03),
FIRST awards (R29), Small Business Innovation Research grants (R43/44),
National Research Service Award Individual Fellowships (F32), National
Research Service Award for senior fellows (F33), Career Development Awards
(K04), Physician Scientist Awards (K11), and Individual Dental Scientist
Awards (K15).  Policies that govern research grant programs of the National
Institutes of Health will prevail.
     
APPLICATION AND REVIEW PROCEDURES
     
Applications will be initially reviewed for scientific and technical merit in
accordance with usual NIH peer review procedures for research grants by
appropriate study section.  Review criteria include the significance and
originality of the research goals and approaches; feasibility of the research
and adequacy of the experimental design; training, experience, research
competence, and dedication of the investigator(s); adequacy of available
facilities and study populations; provisions for the protection of human
subjects and the humane care of animals; and appropriateness of the requested
budget.  Applicants are encouraged to include women and minorities in study
designs, if such inclusion is feasible.  For studies which exclude women or
minorities, a clear rationale for exclusion should be provided.
     
Funding decisions will be based on Study Section and National Advisory Council
recommendations regarding scientific merit and program relevance, and the
availability of appropriated funds.
     
Questions concerning this announcement may be addressed to Dr. Patricia Bryant
at the address given below.  Applications for research grants should be
submitted on form PHS-398, and the special instructions for small grants and
FIRST awards should be followed when applicable.  Application forms and
special instructions are available in the business or grants office at most
academic or research institutions, or from the Division of Research Grants,
National Institutes of Health.  Applications will be accepted in accordance
with the customary receipt dates for new applications on an indefinite basis
at the appropriate deadlines for the support mechanisms selected.  For R03's,
there are no set deadlines.

     
     
                 Vol. 18, No. 34, September 29, 1989 - Page 6
The phrase "THE EFFECTS OF ORAL FACTORS ON TASTE AND SMELL" should be typed on
line 2 of the face page of the application.  The original and six copies
should be sent or delivered to:
     
Grants Application Receipt Office
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, Maryland  20892-4500**
     
Applicants interested in studying oral conditions/diseases or dental
treatments as related to taste and smell are encouraged to contact Dr.
Patricia Bryant at the address and phone number indicated:
     
Patricia S. Bryant, Ph.D.
Health Scientist Administrator
Craniofacial Anomalies, Pain Control
  and Behavioral Research Branch
National Institute of Dental Research
Westwood Building, Room 506
Bethesda, Maryland  20892-4500
Telephone:  (301) 496-7807
     
Applicants interested in other basic or clinical research issues related to
taste and smell may contact Dr. Jack Pearl for additional information
regarding NIDCD's research priorities.
     
Jack Pearl, Ph.D.
Health Scientist Administrator
Division of Communicative and Neurosensory Disorders
National Institute on Deafness and Other Communication Disorders
Federal Building, Room 1C-14
7550 Wisconsin Avenue
Bethesda, Maryland  20892
Telephone:  (301) 496-5061
     
This program is described in the Catalog of Federal Assistance No. 13.122.
Awards will be made under authorization of the Public Health Service Act,
Title III.  Section 301 (Public Law 78-410, as amended), the Small Business
Innovation Development Act, Public Law 97-219 and the Health Research
Extension Act of 1985, Section 453 and administered under PHS grants policies
and Federal Regulations 42 CFR Part 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.

NASAL CHEMORECEPTION:  REGENERATION AND TROPHIC INTERACTIONS
     
P.T. 34; K.W. 0760075, 1002034, 0710085, 1002008
     
National Institute on Deafness and Other Communication Disorders
     
PURPOSE
     
The National Institute on Deafness and Other Communication Disorders (NIDCD)
encourages both new and established investigators to submit applications
related to the mechanisms of the regeneration cycle of nasal chemosensory
receptor neurons and the trophic interactions between these neurons and other
cells.  New opportunities for understanding the mechanisms of this plasticity
and its development have been provided by advances in the concepts,
approaches, and methods of contemporary neurobiology, for example, molecular
neurobiology.
     
BACKGROUND
     
The vertebrate olfactory epithelium is unique.  This neuroepithelium retains
its juvenile capability to form functional olfactory receptor neurons from
stem cells throughout adult life.  The differentiating cells become fully
mature bipolar neurons at the time of synaptic contact with the olfactory
bulb.  Turnover of the receptor neurons increases after their mass
destruction.
     
Trophic interactions in the olfactory system begin in early life and continue
through adulthood.  The embryonic telencephalon does not achieve its normal
size in the absence of the olfactory placode.  Olfactory receptor neurons
exhibit a powerful trophic influence on the formation and maintenance of the
olfactory bulb.  Transplants of olfactory receptor neurons remodel the
morphology of non-olfactory regions of the mature forebrain.  The expression
     
                 Vol. 18, No. 34, September 29, 1989 - Page 7
of neurotransmitters in the bulb is altered by chemical or surgical
destruction of the olfactory receptor neurons and by neonatal closure of the
nares.  When adult forebrain tissue beneath the bulb is innervated by
olfactory receptor neurons after bulbectomy, the input induces the forebrain
to begin producing tyrosine hydroxylase.  Some of these interactions are
reciprocal.  For example, the morphology of the mature olfactory epithelium is
altered markedly by bulbectomy.
     
The olfactory placode is the source of four nasal chemosensory nerves:
olfactory, septal, vomeronasal, and terminal nerves.  Like olfactory receptor
neurons, vomeronasal receptor neurons regenerate and could have a trophic
influence on accessory olfactory bulb and other brain cells.
     
The development of the concepts, approaches, and methods of modern
neurobiology has provided the opportunity to learn more about the mechanisms
of regeneration and trophic interactions in nasal chemoreception.  For
example, the methods of molecular biology and molecular genetics are being
used to identify and characterize developmentally regulated complementary DNAs
of olfactory receptor neurons and brain.  In vitro cultures of dissociated
olfactory receptor neurons and organotypic preparations of olfactory tissue
are being developed.  High voltage electron microscopy and temporal
videomicroscopy can be utilized to visualize the elements of the nasal
chemosensory system.  Several biochemical markers of olfactory receptor
neurons have been identified; some of these markers are specific for olfactory
receptor neurons, synaptogenic processes, or specific phases of the
regeneration cycle.  Patch clamping can be utilized to study openings and
closings in single ion channels.  Voltage sensitive dyes permit the study of
simultaneous neural responses in populations of neurons in both the olfactory
epithelium and the bulb.  The robust ability of animals to detect and
differentiate odorants has provided a valuable means to gauge olfactory
function with behavioral tests during the regeneration cycle of olfactory
receptor neurons.
     
RESEARCH GOALS AND SCOPE
     
Studies of the regeneration of nasal chemosensory neurons and the trophic
interactions between these neurons and brain and other cells are important for
understanding the normal development of nasal chemoreception, its plasticity,
and the response of the chemosensory system to injury and age-related
conditions.  This knowledge is vital for developing therapeutic approaches for
repairing damage to the system and may provide clues to what helps and hinders
repair of damage in the less plastic parts of the nervous system.
     
Areas of interest in the regeneration and trophic interactions of nasal
chemoreceptor neurons include, but are not limited to:
     
 o Tissue interactions in the formation of the olfactory
   placode.
 o Identification and characterization of chemical
   substances involved in the development of the olfactory
   placode.
 o Mechanisms in normal degeneration of the chemoreceptor
   neurons and in degeneration after various injuries.
 o Mechanisms of activation and deactivation of
   regeneration.
 o Migration of cells.
 o Differentiation of regenerating chemoreceptor neurons.
 o Quantitative relations between stem cells and progeny.
 o Ultrastructural and biochemical probes to characterize
   various cells in the nasal epithelium during development
   and regeneration.
 o Trophic and tropic factors in regeneration.
 o Innervation of target neurons by regenerated
   chemoreceptor neurons and restoration of physiological
   and behavioral function.
 o Synthesis of neurotransmitters in chemoreceptor neurons
   and their target cells.
 o Interactions of regeneration with conditions such as age,
   gender, and hormonal status.
     
MECHANISMS OF SUPPORT
     
Applications may be submitted for conventional support mechanisms of the
National Institutes of Health (NIH):  individual research project grant (RO1),
First Independent Research Support and Transition Award (R29), Program Project
(PO1), Research Career Development Award (KO4), Clinical Investigator
Development Award (KO8), Individual National Research Service Award (F32), and
Senior Fellowship National Research Service Award (F33).  Potential applicants
     
                 Vol. 18, No. 34, September 29, 1989 - Page 8
for program project grants should contact NIDCD staff very early in the
planning stages.  The NIH policies that govern the programs will prevail.
Funding is contingent upon receipt of proposals of high scientific merit,
responsiveness to this announcement, relevance to the program, and
availability of appropriated funds.
     
APPLICATION SUBMISSION AND REVIEW PROCEDURES
     
Use the standard application forms (PHS 398, rev.  10/88) as instructed in the
application kits.  These kits are available from the business offices or the
offices of sponsored research of most institutions, or from the Division of
Research Grants, National Institutes of Health.  Type "NASAL CHEMORECPTION:
REGENERATION AND TROPHIC INTERACTIONS" in Item #2 of the application face page
and check the "YES" box.  Applications should be responsive to the program
announcement and the Abstract of the Research Plan should contain a clear
statement relating the proposed research to nasal chemoreception of interest
to NIDCD.  Use the mailing label in the kits to mail the applications to the
Division of Research Grants.
     
Applications should be submitted according to the receipt dates identified in
the application kits.  The applications will be reviewed as specified in the
schedules of the application kits.  In the event of questions, investigators
may call or write:
     
Jack Pearl, Ph.D.
National Institute on Deafness and Other Communication Disorders
National Institutes of Health
Federal Building, Room 1C-14
Bethesda, Maryland 20892
Telephone:  (301) 496-5061
     
This program is described in the Catalog of Federal Domestic Assistance No.
13.85.4, Biological Basis Research, NINCDS.  Awards will be made under the
authority of the Public Health Service Act, Title IV, Section 301 (Public Law
78-410, as amended; 42 USC 241) and administered under PHS grant policies and
Federal Regulations 42 CFR Part 52 and 45 CFR Part 74.  This program is not
subject to Health Systems Agency Review.

**THE MAILING ADDRESS GIVEN FOR SENDING APPLICATIONS TO THE DIVISION OF
RESEARCH GRANTS OR CONTACTING PROGRAM STAFF IN THE WESTWOOD BUILDING IS THE
CENTRAL MAILING ADDRESS FOR THE NATIONAL INSTITUTES OF HEALTH.  APPLICANTS WHO
USE EXPRESS MAIL OR A COURIER SERVICE ARE ADVISED TO FOLLOW THE CARRIER'S
REQUIREMENTS FOR SHOWING A STREET ADDRESS.  THE ADDRESS FOR THE WESTWOOD
BUILDING IS:
     
5333 Westbard Avenue
Bethesda, Maryland 20816

     

     

     

     

     

     

     

     

     

     
     
                 Vol. 18, No. 34, September 29, 1989 - Page 9