This Program Announcement expires on November 30, 2004, unless reissued.

PLASTICITY OF HUMAN STEM CELLS IN THE NERVOUS SYSTEM

Release Date:  December 3, 2001

PA NUMBER:  PA-02-025

National Institute of Neurological Disorders and Stroke
 (http://www.ninds.nih.gov)
National Institute on Aging
 (http://www.nia.nih.gov)
National Institute of Mental Health
 (http://www.nimh.nih.gov)
National Heart, Lung, and Blood Institute
 (http://www.nhlbi.nih.gov)

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 Neurological Disorders and Stroke (NINDS), the 
National Institute on Aging (NIA), the National Institute of Mental Health 
(NIMH) and the National Heart, Lung, and Blood Institute (NHLBI) invite 
applications for studies on the plasticity and behavior of human stem cells, 
and regulation of their replication, differentiation and function in the 
nervous system. Because of their ability to generate neurons and glia, stem 
cells are promising candidates for the development of cellular and genetic 
therapies for neurological disorders, including congenital, 
neurodevelopmental, neuropsychiatric and neurodegenerative diseases, as well 
as neuroregulatory problems in heart, lung, and blood diseases, and sleep 
disorders. Animal studies demonstrate that stem or progenitor cells can be 
derived from a variety of tissues and from hosts of different ages; however, 
the requirements and potential for differentiation of each cell type appears 
to be unique. In a recently-issued Program Announcement (PA-01-078)), NINDS 
and other institutes at NIH invited studies to investigate the influence of 
extrinsic signals in the nervous system on the biology of non-human stem 
cells. Development of treatments for human conditions ultimately will require 
understanding the biology of human stem cells. To achieve this goal, NINDS, 
NIA, NIMH and NHLBI encourage applications to study the fundamental 
properties of all classes of human stem cells, and to confirm, extend, and 
compare the behavior of human stem cells that are derived from different 
sources and ages or exposed to different regimes in vitro and in vivo. Of 
high priority are studies to develop methods for identifying, isolating and 
characterizing specific human precursor populations at intermediate stages of 
differentiation into neurons and glia.  Because our current understanding of 
stem cell biology comes mainly from studies conducted on murine stem cells, a 
comparison between human and non-human cells will be crucial for translating 
the results of animal studies to clinical trials. This Program Announcement 
(PA) invites applications for support of research that characterizes 
cellular, molecular and genetic mechanisms that allow human stem and 
precursor cells to express plasticity and lineage choices. Projects that 
address comparisons between different classes of human stem cells, and 
between human and non-human stem cells would also be directly relevant to 
this PA.

RESEARCH OBJECTIVES

Background

Stem cell research offers enormous potential for treating a host of 
congenital, developmental, psychiatric or degenerative diseases for which 
there are no cures. In animal studies, multipotent progenitor cells from many 
different sources have been reported to generate cells with neuronal or glial 
properties, raising expectations that they could be used to replace lost 
neurons and glia, repair defective circuits, and restore functions 
compromised by abnormal development, age, physical damage or disease. In 
addition to cell and tissue therapy, the ability to selectively produce one 
or more differentiated cell types at will from pluripotent stem cells would 
be of clinical importance in investigating the effects of drugs and 
environmental factors on differentiation and cell function in the human 
nervous system.  

Major challenges have to be overcome before any human cells can be harnessed 
and translated to meaningful treatments for patients.  These challenges 
include identifying the optimal type of stem cell or stem cell derivative for 
specific assays and therapies for individual disorders, harvesting and 
growing sufficient quantities of the appropriate cell type, deciding the best 
therapeutic strategy for each condition to be treated, and assessing the 
often-unexpected side effects that may arise when such versatile cells are 
introduced into a patient. In addition, examples of the enormous plasticity 
exhibited by stem cells raise fundamental questions about the comparative 
potential of precursor cells derived from different sources and different 
stages of development; the nature of the conditions that regulates stem cell 
behavior; and the genetic, molecular and cellular mechanisms that result in 
functional integration within the host nervous system over the lifespan of 
the organism. 

Of the many types of progenitor cells competent to develop neuronal and glial 
features, embryonic stem (ES) cells, derived from embryos at the blastocyst 
stage, may have the broadest natural potential because, during development, 
they normally produce all the cells of an organism. These pluripotent cell 
lines are characterized by nearly unlimited self-renewal and differentiation 
capacity.  During differentiation in vitro, mouse and human ES cells express 
properties of mature tissues such as muscles, several classes of neurons, 
glia, pancreatic islet cells, cartilage and blood. When transplanted into the 
central nervous system (CNS), ES cells that have been coaxed along an 
oligodendrocytic lineage will form myelin and ensheath axons. Some improved 
function was reported in rodent models of demyelination and spinal cord 
injury that received these ES cell-derived transplants. However, how the 
transplanted cells contributed to the restoration of function is unclear.     

Another source of progenitors are neural stem cells that are derived from 
neurogenic regions in the developing and adult CNS. They integrate seamlessly 
into the host when transplanted into the developing nervous system, but their 
fate appears highly dependent upon the local environment that they encounter. 
This is particularly true when these cells are introduced into the adult CNS.  
Cells that can become neurons in the hippocampus, generate only astrocytes 
when placed into the spinal cord. Under appropriate conditions, some neural 
stem cells can even develop into non-neural cell types.  

Of particular interest are recent reports from a number of investigators that 
stem cells present in adult, non-neuronal tissues also appear to show 
surprising plasticity or versatility.  For example, under specific culture 
conditions, bone marrow stromal cells can give rise to cells with neuronal or 
glial features.  Following bone marrow transplantation, donor-derived cells 
could be found in many tissues including the CNS, skeletal muscle, liver, 
heart, vascular endothelia, and bone. One group reports that systemic 
injections of bone marrow stromal cells resulted in significant functional 
recovery in a rodent model of ischemia. Before we can design therapies using 
human stem cells, we must understand how "plastic" or malleable are these 
different classes of cells, the environmental cues that drive their choice of 
fates, and how reversible are these fates.    

For unknown reasons, select populations of cells are destroyed in specific 
neurological disorders and diseases - dopaminergic neurons in Parkinson's 
Disease (PD), cholinergic neurons in Alzheimer's Disease(AD), motor neurons 
in Amyotrophic Lateral Sclerosis (ALS) and myelinating oligodendrocytes in 
Multiple Sclerosis (MS). Because there is great diversity of neurons and 
glia, studies to develop treatments for these and other diseases with less 
well defined etiologies will require the characterization and acquisition of 
unique populations of neurons and glia. While dopaminergic neurons clearly 
are the target of studies on PD, defining the specific features of the 
dopaminergic neurons needed to treat PD is less obvious.  Each neuronal and 
glial phenotype is defined by a constellation of morphological, biochemical, 
genetic, and electro-physiological properties, and the functional 
significance/impact of a neuronal population depends on connectivity with 
appropriate afferent and efferent populations. It is necessary to determine 
the particular stem cell and protocol to generate a differentiated phenotype 
that best replicates the significant properties of the endogenous target 
cell. This requires direct comparison in the same in vitro and in vivo assay 
systems between the numerous types of stem and progenitor cells.  The easiest 
features to evaluate include morphology, biochemical and gene expression, and 
physiology.  Less often described are quantification of protein and gene 
levels, acquisition and maintenance of phenotype over time, cell division and 
migration, and the simultaneous tracking of multiple properties in a 
population of cells.  Least studied is the functional integration and 
functional consequences of the transplanted cells in the host, and the long-
term behavior of the transplanted population within the host. At present we 
know little about the biology and comparative differentiation potential of 
different types of stem cells, or their potential for use in developing 
treatments for neurological disease.  

Much of our understanding of the neural potential of different stem cells 
comes from animal studies. It is still unclear if the many varieties of stem 
cells described in animals are also present in humans, or how they can be 
harvested, expanded, purified and induced to differentiate into neurons and 
glia. We lack an understanding of the conditions required to support the 
development of human cells along specific lineages in a reproducible manner. 
Because most studies on human stem cells have been conducted in culture, it 
is unclear whether the differentiated cells will persist, how they will 
behave in the environment of the healthy brain, or their potential in the 
nervous system altered by trauma, disease, or age.  A few studies, carried 
out in animal models of dysfunction, hold promise that differentiated donor 
cells can maintain neuronal markers for long periods in vivo.  However, there 
is as yet no demonstration that these cells integrate functionally into the 
existing nervous system of the host and contribute to behavioral recovery. 
There are few studies on the long-term fates of any transplanted cells within 
the nervous system or at other sites within the host.

Objectives and Scope

This Program Announcement is intended to promote studies of human stem cell 
biology and the regulation and control of stem cells in the nervous system.   
Of special interest are research efforts on cellular, molecular and genetic 
mechanisms that influence the lineage choices of human stem cells, and the 
development of methods for isolating specific cell populations, and studies 
that demonstrate or enhance the safety of human stem cells in treatments for 
neurological conditions. The following examples illustrate areas that are of 
high interest; other innovative projects are also encouraged. 

o  Comparison of the mitotic potential and fates of different types of human 
stem and progenitor cells in vitro and in vivo in the CNS.

o  Comparison of the structural and functional integration of different types 
of human progenitor cells into the healthy versus the injured or diseased 
host nervous system. 

o  Determination of the functional properties of human progenitor cells 
implanted during progressive developmental stages of the host CNS, and with 
aging.

o  Comparison of the functional properties of human stem and precursor cells 
implanted at different stages of differentiation along neuronal or glial 
lineages.

o  Comparison of the behavior of human stem cells with that of their non-
human counterparts in vitro and in vivo.

o  Investigation of the ability of different human stem cells to revert to a 
more plastic, multipotent state, under normal conditions and following 
injury.

o  Examination of changes in gene and protein expression as human stem and 
progenitor cells differentiate along specific neuronal and glial lineages.
 
o  Identification of signals, signaling pathway components and 
transcriptional factors that regulate the fate(s) of transplanted human stem 
cells and their derivatives.

o  Development of assays and markers that permit accurate and reliable 
characterization of the state of differentiation of human stem or neural 
precursor cells.

o  Development of methods for identifying, isolating and enriching select 
human precursor populations, intermediate states, and differentiated neuronal 
and glial phenotypes.  

o  Development of a public database of gene expression patterns for human 
stem cells as they differentiate and mature into specific neuronal and glial 
fates.  

o  Development of informatics models that integrate the results from studies 
of different human and non-human stem and neural precursor cell types.

o  Use of animal model systems of neurological and neuropsychiatric disorders 
for screening and comparing the functional capabilities of implanted human 
stem cells and their progeny.

o  Assessment of the long-term fates and the consequences of transplanted 
human cells and their progeny in the nervous system, and in ectopic sites 
within the host. 

o  Assessment of the connectivity and integration of transplanted cells 
within the host nervous system and across the lifespan. 

o  Assessment and comparison of the immune responses generated by different 
human stem cells and their progeny in the host.

o  Assessment of the behavior of host cells in response to the short-term and 
long-term presence of transplanted human stem cells and/or their derivatives. 

SPECIAL REQUIREMENTS

Use of human embryonic stem cells (hESCs): Criteria for federal funding of 
research on hESCs can be found at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  
All cell lines that meet these criteria and are therefore eligible for research 
with federal funding are identified and registered in the NIH Human Embryonic 
Stem Cell Registry (http://escr.nih.gov).  NIH has established a website 
(http://grants.nih.gov/grants/stem_cell_faqs.htm) that provides information 
in the form of answers to frequently asked questions about implementation 
issues for human embryonic stem cell research (see also: 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-014.html). Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for funding.  Each approved cell line is 
specifically identified by an NIH code in the Registry.  It is the 
responsibility of the applicant to provide in their application the official 
NIH identifier(s)for the hESC line(s)that they will use as found in the NIH 
Registry (http://escr.nih.gov).  Applications that do not provide this 
information will be returned without review. 

MECHANISM OF SUPPORT

The Exploratory/Developmental Grants (R21) mechanism and the Research Project 
(R01) grant mechanism will be used to support projects under this Program 
Announcement(PA).  Under these mechanisms, responsibility for the planning, 
direction, and execution of the proposed project will be solely that of the 
applicant.  The proposed project period during which the research will be 
conducted should adequately reflect the time required to accomplish the 
stated goals and should be no more than 5 years for R01 grants. The R21 
grants are one-time awards to support innovative, high impact research 
projects that would either 1) generate pilot data to assess the feasibility 
of a novel avenue of investigation, 2)involve high risk experiments that 
could lead to a breakthrough in a particular field, or 3) demonstrate the 
feasibility of new technologies that could have major impact in a specific 
area. For this PA, participating NIH institutes will use the NINDS guidelines 
for the R21 mechanism, which can be found at 
http://www.ninds.nih.gov/funding/r21guidelines.htm.  As described in these 
guidelines, R21 proposals are limited to two years with a maximum of $125,000 
direct costs per year.  This program is appropriate both for new investigators 
seeking to establish independent research careers and for established 
investigators wishing to explore new areas of neuroscience or develop novel 
technologies. 

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.

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.  

INQUIRIES

Inquiries are encouraged.  The opportunity to clarify any issues or questions 
from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Arlene Y. Chiu, Ph.D.
Program Director, 
Repair and Plasticity Program
National Institute of Neurological Disorders and Stroke
Neuroscience Center, Room 2206, MSC 9525
Bethesda, MD  20892-9525
Telephone:  (301) 496-1447
FAX:  (301) 480-1080
Email:  chiua@ninds.nih.gov

Bradley C. Wise, Ph.D.
Program Director, Fundamental Neuroscience
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging
7201 Wisconsin Avenue, Suite 3C307 MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-9350
FAX:  (301) 496-1494
Email:  wiseb@nia.nih.gov

Beth-Anne Sieber, Ph.D.
Chief, Developmental Neurobiology Program
National Institute of Mental Health
Neuroscience Center, Room 7186, MSC 9641
Bethesda, MD  20892-9641
Telephone:  (301) 443-5288
FAX:  (301) 402-4740
Email:  sieberb@helix.nih.gov

John W. Thomas, Ph.D.
Blood Diseases Program
Division of Blood Diseases and Resources
National Heart, Lung, Blood Institute
Two Rockledge Centre, Room 10154, MSC 7950
6701 Rockledge Drive
Bethesda, MD  20892-7950
Telephone:  (301) 435-0050
FAX:  (301) 451-5453
Email:  ThomasJ@nhlbi.nih.gov

Direct inquiries regarding fiscal matters to:

Rita Sisco
Grants Management Specialist
Grants Management Branch , DER 
National Institute of Neurological Disorders and Stroke
Neuroscience Center, Room 3290, MSC 9537
Telephone:  (301) 496-9231
FAX:  (301) 402-0219
Email:  rr46w@nih.gov
     
Linda Whipp
Grants Management Officer
Grants and Contracts Management Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2N212, MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-1472
FAX:  (301) 402-3672
Email:  lw17m@nih.gov

Diana S. Trunnell
Grants Management Branch
National Institute of Mental Health
6001 Executive Boulevard, Room 6115, MSC 9605
Bethesda, MD  20892-9605
Telephone:  (301) 443-2805
FAX:  (301) 443-6885
Email:  Diana_Trunnell@nih.gov

Suzanne A. White
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7154 (MSC 7926)
Bethesda, MD  20892-7926
Telephone:  (301) 435-0166
FAX:  (301) 480-3310
Email:  WhiteSa@NHLBI.NIH.GOV 

APPLICATION PROCEDURES

The PHS 398 research grant application instructions and forms (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html must 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 format. 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.

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 or Center (IC) program staff before submitting the application, 
i.e, as plans for the study are being developed. Furthermore, the application 
must obtain agreement from the IC staff that the IC 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 or Center who agreed to accept assignment of the application.
The current policy on accepting applications requesting $500K or more 
requires PIs to seek agreement from IC staff at least 6 weeks prior to 
submission date. Refer to the NIH Guide for Grants and Contracts, October 16, 
2001 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html.  

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)

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.  

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, for R01 applications, 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.

(6) For R21 applications:  Could these high risk experiments lead to a 
breakthrough in the field? Could the proposed studies demonstrate the 
feasibility of new technologies that could have a major impact in a specific 
area?

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.

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 clinical research 
projects unless a clear and compelling justification is 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 clinical research should read the AMENDMENT "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research - Amended, October, 2001," published in the NIH Guide for Grants and 
Contracts on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); 
a complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of 
clinical research; updated racial and ethnic categories in compliance with 
the new OMB standards; clarification of language governing NIH-defined Phase 
III clinical trials consistent with the new PHS Form 398; and updated roles 
and responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must 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) investigators must report annual accrual and progress in conducting 
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 IN THE PROTECTION OF HUMAN RESEARCH 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 available in the NIH Guide for Grants 
an Contracts, June 5, 2000 (Revised August 25, 2000), available at:  
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.
     
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), " Plasticity of human stem cells in the nervous system," is related to 
several of the priority areas including working toward improving life 
expectancy and quality of life of patients disabled by neurological 
disorders. Potential applicants may obtain a copy of "Healthy People 2010"at 
http://www.health.gov/healthypeople/.

AUTHORITY AND REGULATIONS 

This program is described in the Catalog of Federal Domestic Assistance No. 
93.853, 93.866, 93.242 and 93.839. 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 NIH Grants Policy Statement is available at 
http://grants.nih.gov/grants/policy/policy.htm. This document includes 
general information about the grant application and review process; 
information on the terms and conditions that apply to NIH grants and 
cooperative agreements; and a listing of pertinent offices and officials at 
the NIH.

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.


Return to Volume Index

Return to NIH Guide Main Index


Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.