HEMATOPOIETIC CELL LINEAGE GENOME ANATOMY PROJECTS

Release Date:  October 9, 2001

RFA:  RFA-DK-02-018

National Institute of Diabetes and Digestive and Kidney Diseases

Letter of Intent Receipt Date:  February 15, 2002
Application Receipt Date:       March 15, 2002

PURPOSE

The National Institute of Diabetes and Digestive and Kidney Diseases 
(NIDDK) invites Cooperative Agreement Applications (U01) for Adult 
Hematopoietic Cell Lineage Genome Anatomy Projects (HCLGAP) that will 
participate in the discovery of the processes necessary for the self-
renewal and differentiation of hematopoietic stem cells (HSCs) and other 
cells in the hematopoietic lineage in health and disease.  The specific 
goals of the projects will be to develop the necessary biological 
procedures and reagents for characterization of cells of the hematopoietic 
lineage (HCL) and to characterize gene expression patterns in these cells 
using advanced technologies and bioinformatics techniques. Because of the 
nature of the research questions, it is expected that potential applicants 
will include investigators with expertise in the biology of stem and 
progenitor cells, genomics experts, and investigators having substantial 
expertise in bioinformatics.  The components of the GAPs will work 
together as a consortium to serve as a resource to provide reagents and 
databases that will be made available to the larger research community.  

The Human Genome Project and similar work in other species have made it 
possible to address in new ways the important biological problems of how 
small founder populations of stem cells differentiate into mature blood 
cell types, and the effects of age and disease on this capacity.  Recent 
advances in stem cell biology have demonstrated two important principles.  
First, work in model experimental organisms suggests that some critical 
molecules that regulate organ development are evolutionarily conserved.  
Second, there is emerging evidence that stem cells of different tissues 
may share some common basic molecular mechanisms that allow them to self-
renew in the presence of appropriate environmental cues.  The elucidation 
of these mechanisms offers the promise of providing a complete 
understanding of the factors that maintain normal tissues in health and 
the promise for novel approaches to the study of pathogenesis and 
treatment of human diseases.  Therefore, the aim of these projects will be 
to accelerate progress toward identification and characterization of stem 
and progenitor cells and factors that regulate self-renewal, development 
and differentiation.  HCLGAPs will be expected to collaborate closely with 
related NIDDK GAPs in other systems as well as the GAPs funded under the 
related RFA-DK-02-027, which currently is soliciting proposals to 
characterize the genome anatomy of the gastrointestinal epithelium, liver, 
exocrine pancreas, and kidney and urologic tissues, including prostate and 
bladder (http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-02-027.html).

This grant award mechanism will support characterization of HSCs and HSC 
cell lines at multiple stages of differentiation, determination of gene 
expression patterns in those cells, and development of appropriate 
functional genomics tools to characterize the genes expressed.  In 
addition, this resource will provide bioinformatics links to existing NIH-
supported genomics databases and make relevant biomarkers and genomics 
tools available to be used by researchers investigating both normal and 
diseased tissue.

ELIGIBILITY REQUIREMENTS

Applications may be submitted from either domestic or foreign 
institutions, 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.

All current policies and requirements that govern the research grant 
programs of the National Institutes of Health (NIH) will apply to grants 
awarded under this RFA.  Among the disciplines and expertise that may be 
appropriate for this program are hematology, internal medicine, 
pediatrics, genetics, pathology and related scientific disciplines, 
developmental biology and other biological sciences, as well as 
bioinformatics and computing. 

MECHANISM OF SUPPORT

This RFA will use the NIH cooperative research (U01) award mechanism of 
support, an “assistance” mechanism (rather than an “acquisition” 
mechanism) in which substantial NIH scientific and/or programmatic 
involvement with the awardee is anticipated during performance of the 
activity.  Under the cooperative agreement, the NIH purpose is to support 
and stimulate the research activity of the recipients by involvement in 
the activity and otherwise working jointly with the award recipients in a 
partner role, but it is not to assume direction, prime responsibility, or 
a dominant role in the activity.  Details of the responsibilities, 
relationships and governance of the study to be funded under cooperative 
agreements are discussed below under “Terms and Conditions of Award.”

The total project period for an application submitted in response to this 
RFA may not exceed 3 years. This is a one-time solicitation.  At this 
time, the NIDDK has not determined whether or how this solicitation will 
be continued beyond the present RFA. The maximum dollar request for any 
single application is limited to $750,000 direct costs for the initial 
budget period and $2.25 million direct costs for the entire project 
period.  Projects of varying budget and size are encouraged, and smaller, 
more narrowly focused applications will be considered.  The anticipated 
award date is September 30, 2002.

FUNDS AVAILABLE

For FY 2002, $2M in total costs will be committed to fund applications 
submitted in response to this RFA.  Since proposals for projects of 
various sizes are encouraged, it is anticipated that 2 - 5 awards will be 
made.  Final award levels are subject to change due to budgetary, 
administrative and/or scientific considerations, and are dependent upon 
the receipt of a sufficient number of applications of high scientific 
merit.  It is expected that any major equipment costs will be incorporated 
in the first year budget, and that subsequent year budgets should be 
related to the anticipated level of library production and sequencing.  
Although this program is provided for in the financial plans of the NIDDK, 
the award of grants pursuant to this RFA is contingent upon the 
availability of funds for this purpose.

RESEARCH OBJECTIVES

Background

On September 19, 2000, the NIDDK convened a Working Group of its National 
Advisory Council to develop strategic plans for several cross-cutting 
areas of research, including Stem Cell and Developmental Biology 
(http://www.niddk.nih.gov/federal/planning/stemcell.htm).  The primary 
recommendation of this group was that NIDDK should catalyze a nation-wide 
effort to characterize the molecular and cellular features of stem cells 
during and following development of the pancreas, liver, stomach and 
intestine, kidney and GU tract, bone, and hematopoietic tissues.  The goal 
is to provide entirely new strategies for repairing or replacing damaged 
tissues or organs in individuals of all ages, and new insights about 
pathologic processes underlying disordered development, disordered 
maintenance, and neoplastic transformation of these tissues or organs.

Two of the research activities recommended in the plan are 1) Sponsorship 
of Genome Anatomy Projects designed to profile expression of mRNA and 
proteins in recovered progenitor cell populations in developing and adult 
normal tissues. GAP projects should generate searchable, annotated, 
Internet-accessible databases of expressed genes that can be compared to 
databases obtained from diseased tissues from model organisms and humans, 
and 2) An additional GAP agenda should be to support efforts to develop 
broadly applicable methods for amplifying mRNAs from single or small 
numbers of recovered progenitor cells so that gene expression profiling 
can be performed. GAPs should help develop sensitive methods for rapid 
follow-up confirmation of cellular patterns of gene expression in tissues 
from model organisms and humans: the results should be incorporated into 
easily searched and clearly illustrated databases. This RFA meets the 
recommendations in hematopoiesis.

Both the National Cancer Institute and the NIDDK have established GAPs to 
accelerate the pace of discovery of genes expressed in specific tissues, 
such as tumors or the endocrine pancreas, and to exploit the sequence data 
emanating from the Human Genome Project.  The GAPs foster the development 
of national networks of labs that characterize tissue-specific gene 
expression and identify novel transcripts.  In addition, GAP researchers 
elucidate patterns of gene expression that lend insight into developmental 
programs and disease progression, and that may eventually be useful in 
diagnosis and treatment of disease.  The bioinformatics systems associated 
with each GAP ensure that all of the data produced is available to 
researchers worldwide soon after it is generated in the laboratory.  

HSCs are critical models for fundamental understanding of normal 
biological and disease processes and such research is important to provide 
the tools for studies of basic mechanisms of development and function. The 
ability to control differentiation and sort the differentiated cells from 
undifferentiated precursor adult HSCs holds great potential for 
therapeutics, particularly involving tissue replacement, and gene therapy.  
This area of research, with its potential for therapeutic use, will 
require ready accessibility of cells of the hematopoietic stem cell 
lineage (HCL) to understand their developmental potential and the control 
of that potential.  Methods that can be used to characterize these 
precursor cells, and to recognize and sort them from other cells in vivo, 
are improving and will be invaluable to research, as well as being 
potentially valuable in tissue replacement efforts.  

New in vivo models will be important for studying and assaying stem cell 
function.  New methods are needed for recovering stem cells and cell 
populations that allow stem cells to maintain their capacity for both 
self-renewal and differentiation ex vivo.   Thus it is essential to 
characterize genomic features of stem cells and their committed daughters.  
The status of research on stem cells or progenitor cells in different 
organ and tissues varies widely.  Hematopoiesis is among the best-
understood biological systems in mammals and its experimental analysis is 
facilitated by the availability of excellent ex vivo and in vivo models. 
It is an evolutionarily conserved process that can be studied more easily 
than the development of other organs, based on the accessibility of the 
cells, and its study has laid the foundation for much of the basic science 
of stem cell biology.  

The gold standard for the measure of hematopoietic stem cell activity is 
the capability of both short-term and long-term repopulation of a lethally 
irradiated animal, but other surrogate assays have been useful.  
Purification of adult HSCs through the use of monoclonal antibodies has 
been accomplished, however imperfectly, and lineage-specific progenitors 
have been purified recently. In addition, recent studies appear to have 
demonstrated surprising plasticity of adult stem cell populations within 
certain individual organs.  The adult marrow contains stem cells that are 
committed to hematopoiesis as well as stem cells that are mesenchymal in 
origin.  These adult stem cells have been reported to have the capacity to 
be driven to form cell types of a number of tissues with exogenous 
factors.  Although the process is relatively inefficient in vitro, 
contribution of marrow cells to non-hematopoietic lineages have been 
documented in vivo.  The adult marrow thus may represent an 
undifferentiated tissue derived during embryogenesis that can maintain 
highly plastic stem cell populations from diverse tissues.

Despite recent advances, major obstacles for isolating human hematopoietic 
stem/progenitor cell populations exist, including the lack of 
understanding of the role of cell surface markers. Questions of 
separation, enrichment, or expansion of cells of the hematopoietic cell 
lineage, how to select HSCs with in vivo pharmacologic manipulation, and 
how to expand HSCs ex vivo are critical. Reagents directly related to the 
characterization of cells of the HCL are needed, as are the development 
and standardization of methods for in vitro expansion and characterization 
of the cells for distribution, and the optimization of methods for growth 
and preservation of these cells. 

Hematopoietic stem cells are capable of self-renewal and can give rise to 
multiple differentiated lineages.  To characterize stem/multipotential 
progenitor cells, it is necessary to have quantitative assays (both in 
vitro and in vivo) in which to assess the ability of these cells to: (1) 
give rise to multiple lineages, (2) self-renew, and (3) reconstitute a 
cellular compartment. This RFA will support the development of improved in 
vitro and in vivo clonogenic assays for assessing the potential of stem 
cells to self-renew or differentiate.  Research also should be directed 
toward development of methods such as utilization of DNA microarray 
technology, for assessing the quality, purity, and viability of HSCs for 
transplantation and gene therapy.

The current RFA is designed to stimulate GAPs that will catalogue the gene 
expression in recovered hematopoietic stem cell or progenitor cell 
populations in developing and adult normal tissues and provide that 
information and material, along with relevant functional genomics tools, 
to the larger research community.

Since the databases for the GAPs will perform similar functions, it should 
not be necessary for multiple sites to invent similar database methods in 
parallel.   Therefore, researchers from the GAPs will develop robust and 
generic modules to perform particular tasks, so that all databases share a 
common architecture, regardless of the underlying database platform.   
Although developing a module in a robust and generic manner so that it is 
usable by other projects takes more effort than developing it to work 
within just a single GAP, the modular structure will make it easier for 
the larger research community to search among the data collected by the 
various GAPs supported by the NIDDK, and will facilitate sharing, 
comparisons, and data mining among the GAPs.

Research Objectives and Scope

This RFA is intended to support the cost-effective determination of the 
gene expression profiles in the targeted HSC or progenitor cell 
populations of human or non-human origin and to develop functional genomic 
tools with which to characterize the genes expressed.  Thus, all proposals 
must include separate sections describing each of the listed aspects of 
the project.  It is anticipated that each project will allocate resources 
differently to the various parts of the GAP.  Nevertheless, to the extent 
appropriate for the magnitude of the envisioned project, each proposal 
must include: 

o Characterization and Definition of Cell Populations – Define and/or 
develop specific biomarkers, such as high-specificity antibodies or 
reporter gene constructs, for detection, classification, and isolation of 
HSCs and progenitors specific to particular lineages.  This will include, 
where appropriate, development of reliable and convenient clonogenic 
assays for stem cell populations in developing and adult tissues so that 
these cells can be purified and characterized.  In addition, this part of 
the GAP may include development of methods to maintain ex vivo cell 
populations that retain their pluripotency.

o mRNA Expression Profile – Profile mRNA expression in the relevant cell 
populations and identify novel genes and transcript splice forms 
specifically expressed in the targeted cell population using in silico 
methods, production and sequencing of cDNA libraries, as well as arrays 
and other methods.  Since many of these factors may be expressed at very 
low levels at key stages, strategies should be proposed to increase the 
representation of low abundance transcripts in the cDNA libraries and to 
decrease the redundant sequencing of overrepresented or known genes.  In 
addition, the proposal should describe the development of custom clone 
sets for use in microarrays or other high-throughput gene expression 
assays, and the use of those arrays to characterize changes in gene 
expression patterns in the target cell population during differentiation, 
or disease progression.  Finally, this phase of the project may also 
include efforts to develop and apply single-cell gene expression 
methodologies.

o Histology and Functional Genomics - Develop rapid, sensitive methods for 
in vivo confirmation of patterns of gene expression.  This phase of the 
project may also include the development of one or more gene-specific 
tools, such as reporter gene (e.g. with Green Fluorescent Protein, b-
galactosidase) and antisense constructs, conditional or nonconditional 
knockout mutations, and morpholinos or other inhibitors of expression, for 
characterizing the cells under study and for analyzing the role of 
particular genes.

o Database – Although each GAP will develop its own database to store, 
organize, analyze, or visualize data, this database will be based on 
common modules developed by all the funded GAPs.  The modules will include 
one that allows for Internet-based comparisons of progenitor cell gene 
expression data to similar data obtained from normal and diseased tissues 
from model organisms and humans.  The overall goal is that GAP databases 
should be easy to search and clearly illustrated.  Applicants should 
discuss how they would participate and contribute to this modular approach 
and summarize their experience in this area.  A schedule for rapid 
disposition of sequences and expression data into public databases such as 
GenBank and the Gene Expression Omnibus (GEO) should also be proposed.

o Research Tool Distribution – Develop and distribute to the larger 
research community well-characterized progenitor cells, cDNA clones, and 
high-specificity antibodies.  In addition, the GAP should develop and 
distribute clone sets or long oligonucleotides for printing custom 
microarrays that can be used to identify and characterize the target stem 
cell population during different stages of development and 
differentiation.  Similarly, the GAP should make available to the larger 
research community any functional genomic tools developed, including GFP 
or antisense constructs, knockout cell lines or vectors for gene 
replacement, transgenic animals and other similar reagents or resources 
that can be used to isolate and study the target cells at various stages 
and/or study the role of specific genes.  The selection of sequences for 
custom arrays and reporter constructs should be well-justified and based 
on their utility for research on the relevant stem cell.  The proposal 
should describe plans to develop and maintain supporting informatics and 
easily accessible Web sites that describe available tools and validated 
methods.  Plans for distributing reagents in a timely and economical 
fashion should be included.

o Outreach - A major objective of this RFA is to disseminate the data and 
research reagents generated through each project to the larger research 
community as rapidly as possible.  Therefore, the proposal should describe 
methods for ensuring that the larger research community has access to data 
and available tools generated by the GAP.  In addition, applicants are 
encouraged to describe opportunities for long- and short-term training of 
researchers at all levels to take advantage of these data and reagents.

Data Coordination Plan
 
As part of an Administrative Core, each Gap application should submit 
plans as to the nature of a database that will be used to store, organize, 
analyze, or visualize data that is generated from individual projects for 
the purpose of disseminating information and facilitating data sharing 
within the eventual multiple funded GAPS. The development of appropriate 
bioinformatics will be critical to this element, and a plan for 
implementation of bioinformatics within the first year should be proposed.

SPECIAL REQUIREMENTS

Applicants must indicate their willingness to be part of a Steering 
Committee consisting of representatives of each GAP funded by NIDDK 
through this RFA and through RFA-DK-02-027, and NIH staff.  Semi-annual 
meetings will be held to encourage exchange of information among 
investigators who participate in these programs.  A major goal of these 
meetings is to facilitate progress by providing a forum that will lead to 
sharing skills, ideas, technology, data, and biological reagents.  At the 
meetings, participants also will discuss quality assurance, coordination, 
sharing, means of informing the larger research community of services 
offered by the GAPs, and training.  One special focus of the meetings will 
be on bioinformatics.  Applicants must include travel funds that will 
allow the Principal Investigator and the key research scientist leading 
the bioinformatics effort to participate each year in two one-day meetings 
in Bethesda, Maryland.

During the course of the funding period, technologies will improve, and 
the rate of progress and focus of work supported by the cooperative 
agreement may change.  It is expected that the Principal Investigator(s), 
in consultation with NIDDK program staff, the Steering Committee, and the 
External Advisory Board (see below) will make any necessary adjustments to 
accommodate the changing research environment, to remain focused on 
appropriate goals, to maintain excellent coordination with the other 
projects funded by NIDDK, and to incorporate new technological advances.

A. Interactions

The GAPs, through the Steering Committee, and other subcommittees will: 

o Share bioinformatics expertise and tools to develop robust database 
software as modules to perform particular tasks.  Such modules will be 
able to read and write data in certain common formats, but will be 
independent of the underlying database platform.  These modules will 
provide uniformity of data presentation between the GAPs, and facilitate 
distribution of resources between component Units and with the larger 
research community.  The modules developed may include modules for storing 
and presenting microarray data, cell-type-specific expression profile, 
annotation data for expressed genes, and in vivo expression data, as well 
as various queries or views that are generally useful.

o Define the best practices and develop controlled vocabularies to 
describe genes, tools and reagents, 

o Identify technological impediments to characterizing gene expression, or 
generating appropriate tools, and select strategies to surmount them, 

o Share technological and methodological information both between 
component GAPs and with the larger research community,

o Share molecular tools and constructs between GAPs to avoid unnecessary 
duplication of effort,

At each step, input will be sought from experts both within the GAPs, 
those funded through other NIDDK-sponsored initiatives, such as the 
Functional Genomics of the Developing Endocrine Pancreas (RFA DK-99-007), 
NIDDK Biotechnology Centers (RFA-DK-00-002), and Development of the Gut, 
Liver and Exocrine Pancreas (RFA-DK-01-023), and from the larger research 
community.

B. Genome Anatomy Project Individual Applicant Teams

Each GAP applicant team will be a self-assembled group of investigators 
from one or more institutions who provide a unique mix of complementary 
research experiences.  An applicant team will incorporate an appropriate 
mix of expertise needed to achieve the project’s goals and to contribute 
substantially to achieving the overall GAP goals.  Each team must contain 
expertise in stem cell biology, genomic analysis, and bioinformatics. 

The approaches used to generate the appropriate resources for 
hematopoietic lineage research, and to characterize the gene expression 
profile, will reflect the blend of experience and creativity of the team 
of investigators. 

It is anticipated that some of these proposals will be quite speculative, 
and in some aspects there may be limited preliminary data.  However, 
applications should include sufficient information to indicate that the 
applicant team has sufficient expertise with proposed techniques and that 
the proposed projects are feasible.

C. Data Sharing

Restricted availability of unique research resources, upon which further 
studies are dependent, can impede the advancement of research and delivery 
of medical care.  Sharing biomaterials, data, and software in a timely 
manner has been an essential element in the rapid progress that has been 
made in the genetic analyses of mammalian genomes.  NIH policy requires 
that investigators make unique research resources readily available for 
research purposes to qualified individuals within the scientific community 
after publication [NIH Grants Policy Statement 
(http://grants.nih.gov/grants/policy/nihgps, Principles and Guidelines for 
Recipients of NIH Research Grants and Contracts on Obtaining and 
Disseminating Biomedical Research Resources:  Final Notice, December 1999 
(http://www.ott.nih.gov/policy/rt_guide_final.html)].  Investigators are 
expected to make available biomaterials (constructs, cell lines, etc.) and 
other research resources that can be patented (e.g., software tools, 
expression data) produced in projects funded by this RFA and distribute 
them to the broader scientific community.

The NIH is interested in ensuring that the research resources developed 
through this RFA become readily available to the larger research community 
for further research, development, and application, in the expectation 
that this will lead to products and knowledge of benefit to the public.  
At the same time, NIH recognizes the rights of grantees to elect and 
retain title to subject inventions developed under federal funding under 
the provision of the Bayh-Dole Act.

This RFA has two special requirements regarding research resources 
produced in proposed projects:

(1) Applicants are required to include in their application a specific 
plan by which they will share research resources with the wider scientific 
community, as well as copies of all Material Transfer Agreements used by 
all institutions involved in the application. 

(2) Applicants are required to include a plan addressing if, or how, they 
will exercise their intellectual property rights while making available to 
the broader scientific community patentable research resources.  These 
plans should be consistent with the policies of their institutional 
offices of technology transfer.

The scientific review group will evaluate the adequacy of the proposed 
plans for sharing and data access. Comments on the plan and any concerns 
will be presented in an administrative note in the Summary Statement.  The 
adequacy of the plan will be considered by NIH program staff and will be 
important in determining whether the grant shall be awarded. The sharing 
plan as approved, after negotiation with the applicant when necessary, 
will be a condition of the award.  Evaluation of non-competing 
continuation applications will include assessment of the effectiveness of 
research resource release.

Applicants are reminded that the grantee institution is required to 
disclose each subject invention to NIH within two months after the 
inventor discloses it in writing to grantee institutional personnel 
responsible for patent matters. The NIDDK reserves the right to monitor 
awardee activity in this area to ascertain if patents or patent 
applications are adversely affecting the goals of this RFA.

D. Steering and Other Committees

The Principal Investigator must be willing to participate in a Steering 
Committee that will meet twice each year together with NIH program staff 
to encourage exchange of information among investigators who participate 
in this program.  The Steering Committee may form other committees (for 
example, bioinformatics, technology) that will meet once or twice a year 
either in person or by telephone conference calls.  A major goal of these 
meetings is to facilitate progress by providing a forum for sharing 
skills, ideas, technology, data, and biological reagents.  At the 
meetings, participants will also discuss quality assurance, 
bioinformatics, coordination, and training.  If voting is necessary for an 
action item, NIH Program Scientists will share one vote.

TERMS AND CONDITIONS OF AWARD
 
The following terms and conditions will be incorporated into the award 
statement and provided to the PI(s) and to the institutional official at 
the time of award. These special Terms of Award are in addition to and not 
in lieu of otherwise applicable OMB administrative guidelines, HHS Grant 
Administration Regulations in 45 CFR Parts 74 and 92, and other HHS, PHS, 
and NIH Grant Administration policy statements.

The administrative and funding instrument used for this program is a 
cooperative agreement (U01), an "assistance" mechanism (rather than an 
"acquisition" mechanism) in which substantial NIH scientific and/or 
programmatic involvement with the awardee is anticipated during 
performance of the activity. Under the cooperative agreement, the NIH 
purpose is to support and/or stimulate the recipient"s activity by 
involvement in and otherwise working jointly with the award recipient in a 
partner role, but it is not to assume direction, prime responsibility, or 
a dominant role in the activity.  Consistent with this concept, the 
dominant role and prime responsibility for the activity resides with the 
awardees for the project as a whole, although specific tasks and 
activities in carrying out the studies will be shared among the awardees 
and the NIDDK Program Scientists.

Awardee Rights and Responsibilities

The awardee(s) will have lead responsibilities to define objectives and 
approaches and to plan, conduct, analyze, and publish results, 
interpretations, and conclusions of studies conducted under the terms and 
conditions of the cooperative agreement award.

The PI of each grant will assume responsibility and accountability to the 
applicant organization officials and to the NIDDK for the performance and 
proper conduct of the research supported by the project in accordance with 
the terms and conditions of the award.

The PIs will serve as voting member[s] of the Steering Committee, will 
attend the Planning Meeting and a Steering Committee meeting in the first 
year, and two Steering Committee meetings a year in subsequent years.

The PIs will be responsible for accepting and implementing the goals, 
priorities, procedures, protocols, and policies agreed upon by the 
Steering Committee and subcommittees.

The PIs will be responsible for close coordination and cooperation with 
the other GAPs and with NIH staff.

The PI of each grant will establish an Internal Advisory Committee to 
provide scientific and administrative oversight.  The Internal Advisory 
Committee will be composed of the lead GAP personnel, and other technical 
or research personnel.  These individuals need not be limited to GAP 
participants.  The committee is expected to meet at least monthly, and 
minutes of these meetings will be made available to NIH staff upon 
request.  The Internal Advisory Committee is charged with both 
prioritizing projects and periodically reviewing GAP activities to ensure 
that the objectives outlined in the application are being met.

Awardees will retain custody of and have primary rights to the data 
developed under these awards, subject to Government rights of access 
consistent with current HHS and NIH policies.  However, all awardees must 
adhere to PHS policy for the distribution of unique research resources 
produced with PHS funding as described under Special Requirements.  The 
NIDDK Project Scientist(s), on behalf of the NIDDK, will have the same 
access, privileges and responsibilities regarding the collaborative data 
as the other members of the Steering Committee.

NIH reserves the right to require the transfer of appropriate cell lines, 
reagents, tools and pertinent data that are generated as the result of 
participation in research supported under these awards to an eligible 
third party, in order to preserve these materials and data about them 
and/or to continue the research. Third parties supported under these 
awards must be informed of this right.

Within the first three months of the award period, the PI will be 
responsible for establishing written milestones for the GAP, in 
consultation with NIDDK Program Staff.

Awardees are encouraged to publish and to publicly release and disseminate 
results, data and other products of the study, concordant with the study 
protocol and governance and the approved plan for making data and 
materials available to the scientific community and the NIDDK.  However, 
during or within three years beyond the end date of the project period of 
NIDDK support, unpublished data, unpublished results, data sets not 
previously released, or other study materials or products are to be made 
available to any third party only with the approval of the Steering 
Committee.

Support or other involvement of industry or any other third party in any 
study performed by the GAPs-- e.g., participation by the third party, 
involvement of project resources or citing the name of the project or the 
NIDDK support, or special access to project results, data, findings or 
resources -- may be advantageous and appropriate.  However, except for 
licensing of patents or copyrights, support or involvement of any third 
party will occur only following notification to and concurrence by the 
NIDDK.

Upon completion of the project, the GAPs are expected to put all study 
design materials and procedure manuals into the public domain and/or make 
them available to other investigators, according to the approved plan for 
making data and materials available to the scientific community and the 
NIDDK, for the conduct of research at no charge other than the costs of 
reproduction and distribution.

NIH Staff Responsibilities

NIDDK Project Scientists will have substantial scientific-programmatic 
involvement during conduct of this activity, through technical assistance, 
advice and coordination above and beyond normal program stewardship for 
grants, as described below.  The dominant role and prime responsibility 
for the project as a whole resides with the awardees, although specific 
tasks and activities in carrying out the studies will be shared by 
awardees and the NIDDK.

NIDDK will designate a Project Officer and a Grants Management Specialist 
to provide administrative oversight of the cooperative agreement.

The NIDDK will name a Project Scientist from within the Division of 
Kidney, Urologic and Hematopoietic Diseases, whose function will be to 
assist the Steering Committee in carrying out the study.  The Project 
Scientist will have one vote for all key study group subcommittees.  The 
Project Scientist will have substantial scientific-programmatic 
involvement in quality control, interim data analysis, safety monitoring, 
and final data analysis and interpretation, preparation of publications, 
and coordination and performance monitoring.  The dominant role and prime 
responsibility for these activities resides with the awardees for the 
project as a whole, although specific tasks and activities in carrying out 
the studies will be shared among the awardees and the NIDDK Project 
Scientist.

The NIDDK reserves the right to terminate or curtail the study (or an 
individual award) in the event of (a) failure to develop or implement a 
mutually agreeable collaborative protocol, (b) substantial shortfall in 
participant recruitment, follow-up, data reporting, quality control, or 
other major breach of the protocol, (c) substantive changes in the agreed-
upon protocol with which NIDDK cannot concur, (d) reaching a major study 
endpoint substantially before schedule with persuasive statistical 
significance, or (e) human subject ethical issues that may dictate a 
premature termination.

NIDDK will form an External Advisory Committee, comprised of NIDDK Program 
Staff and other NIH extramural staff with relevant scientific expertise or 
who manage research grant programs that relate scientifically to the goals 
of the GAPs, and outside advisors picked by the NIDDK. The External 
Advisory Committee will meet regularly to review the progress of the GAPs 
and to advise NIDDK Program Staff of scientific developments and 
opportunities that may enhance the achievement of the GAP goals.

NIDDK Project Scientists will be members of the Steering Committee and, as 
determined by that committee, its subcommittees.

NIDDK Project Scientists will coordinate and facilitate the GAPs, attend 
and participate as voting members in all meetings of the Steering 
Committee, and provide liaison between the Steering Committee and the 
External Advisory Committee.

NIDDK Project Scientists will help the Steering Committee develop and 
draft operating policies and policies addressing recurring situations that 
require coordinated action.

NIDDK Project Scientists will review the scientific progress of the 
individual GAPs, review GAPs for compliance with operating policies 
developed by the Steering Committee, and may recommend to the NIDDK to 
withhold support, suspend, or terminate an award for lack of scientific 
progress or failure to adhere to policies established by the Steering 
Committee.

Collaborative Responsibilities

Steering Committee - The NIH Project Scientists and PIs of the GAPs funded 
under this RFA and RFA-DK-02-027 will be responsible for forming a 
Steering Committee as defined below. An arbitration system, as detailed 
below, will be available to resolve disagreements among members of the 
Steering Committee. The Steering Committee will be the main governing 
board of the GAPs.  It will develop collaborative protocols, identify 
technological impediments to success and strategies to overcome them, 
develop shared software tools for disseminating information about the 
GAPs, and identify opportunities for sharing techniques and tools 
developed within each individual GAP.

The Steering Committee will be composed of the PI from each GAP funded 
through this RFA and RFA-DK-02-027, and NIDDK Project Scientists.  The PI 
from each GAP will have one vote.  The NIDDK Program Scientists will share 
one vote.  The Steering Committee will select a chairperson who will be 
someone other than an NIDDK staff member.

The Steering Committee may, as it deems necessary, invite additional, non-
voting scientific advisors to meetings at which research priorities and 
opportunities are discussed. The NIDDK reserves the right to augment the 
scientific or consumer expertise of the Steering Committee when necessary.

There will be two Steering Committee meetings annually, both in the 
Bethesda, MD area at times agreed upon by the Steering Committee and the 
NIDDK.

The first meeting of the PIs from GAPs funded under this RFA and RFA-DK-
02-027 will be a Planning Meeting in the Bethesda, MD area soon after 
grants are awarded. At the Planning Meeting, the Steering Committee will 
be formed and select a chairperson from among the members who represent 
the awardees. At the Planning Meeting, the Steering Committee may: (a) 
draft a charter to detail policies and procedures, a process for 
monitoring compliance with the policies and procedures, and a process for 
recommending that the NIH Program Administrators act on evidence of non-
compliance of any Consortium component with Steering Committee policies, 
(b) agree upon the terms of the charter, (c) discuss the approaches that 
were proposed in the project applications and any relevant new 
information, and set initial priorities for the projects to be pursued and 
for new technologies to be developed, (d) develop a bioinformatics 
subcommittee whose membership will include the key research scientist from 
each GAP responsible for bioinformatics, NIDDK Program Staff, and outside 
advisors as needed.

At their first meeting each year, the Steering Committee will formulate 
plans for any workshops or symposia to be held.

At the second and subsequent meetings, the Steering Committee will refine 
the GAPs’ scientific objectives and implementation as necessary, 
consistent with progress in the individual GAPs and other laboratories, 
and will share information on the status of GAP projects.

The Steering Committee will plan workshops to which non-GAP participants 
will also be invited to (a) enable the GAPs to explore scientific or 
technologic innovation that occurs during the course of the project, (b) 
inform the larger research community of the progress made toward 
development of gene expression profiles and progenitor cell lines, and (c) 
inform the larger research community of any technological advances related 
to implementation of a GAP.  The NIDDK Program Scientists, the External 
Advisory Committee, and other NIH staff will provide the Steering 
Committee with advice on participants for the workshops and symposia. 

The Steering Committee may establish other subcommittees, in addition to 
the bioinformatics subcommittee, as it deems appropriate, NIH Program 
Scientists and other NIH staff who are Steering Committee members will 
serve on subcommittees as they deem appropriate.
 
Arbitration
 
Any disagreement that may arise on scientific and programmatic matters 
within the scope of the cooperative agreement and between award recipients 
and NIDDK may be brought to arbitration.  An arbitration panel will be 
composed of three members: one selected by the GAP Principal Investigator, 
a second member selected by NIDDK, and the third member selected by the 
two prior selected members.  This special arbitration procedure in no way 
affects the awardee"s right to appeal an adverse action that is appealable 
in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS 
regulation at 45 CFR Part 16.

These special Terms of Award are in addition to and not in lieu of 
otherwise applicable OMB administrative guidelines, HHS Grant 
Administration Regulations at 45 CFR Parts 74 and 92, and other HHS and 
NIH Grant Administration policy statements.  

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and 
their sub-populations must be included in all NIH-supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification are provided indicating that 
inclusion is inappropriate with respect to the health of the subjects or 
the purpose of the research. This policy results from the NIH 
Revitalization Act of 1993 (Section 492B of Public Law 103-43).

All investigators proposing research involving human subjects should read 
the UPDATED "NIH Guidelines for Inclusion of Women and Minorities as 
Subjects in Clinical Research," published in the NIH Guide for Grants and 
Contracts on August 2, 2000 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html), 
a complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm: 
The revisions relate to NIH defined Phase III clinical trials and require: 
a) all applications or proposals and/or protocols to provide a description 
of plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable, 
and b) all investigators to report accrual, and to conduct and report 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

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.

NIH POLICY AND GUIDELINES FOR THE USE OF HUMAN FETAL TISSUE 

Applicants must adhere to the current NIH policy and state and federal 
laws governing the use of human fetal tissue in preparing an application 
in response to this RFA.  Information about the use of human fetal tissue 
is available at http://grants.nih.gov/grants/guide/notice-files/not93-235.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 RFA 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.

LETTER OF INTENT 

Prospective applicants are asked to submit, by February 15, 2002 a letter 
of intent that includes a descriptive title of the proposed research, the 
name, address, and telephone number of the Principal Investigator, the 
identities of other key personnel and participating institutions, and the 
number and title of the RFA in response to which the application may be 
submitted.

Although a letter of intent is not required, is not binding, and does not 
enter into the review of a subsequent application, the information that it 
contains allows NIDDK staff to estimate the potential review workload and 
plan the review.

The letter of intent is to be sent to:

Chief, Review Branch 
Division of Extramural Activities, NIDDK
6707 Democracy Boulevard, Rm.715, MSC 5452
Bethesda, MD  20892-5452
(for express/courier service: Bethesda, MD  20817)
Telephone:  (301) 594-8885
FAX:  (301) 480-3505
Email:  CalvoF@extra.niddk.nih.gov

PREAPPLICATION MEETING

The NIDDK strongly encourages all potential applicants to attend a pre-
application Technical Assistance Workshop, to be held in the Washington, 
DC area, time and place to be announced.  Since the concept of these GAPS 
is a relatively new concept for the applicant population, this workshop 
will provide NIDDK staff the opportunity to clarify any perceived 
ambiguities in the RFA and, thereby, enable applicants to present their 
strongest case for support.  NIDDK encourages potential applicants to 
check its web site for future information: 
http://www.niddk.nih.gov/fund/fund.htm#4.  Issues to be discussed include 
application and review procedures, program goals and objectives, the 
technical requirements of GAPs, and funding decision process.  This 
meeting is open to the public and all interested parties are encouraged to 
attend.  A summary of written questions and responses from the 
preapplication meeting, together with responses to questions received in 
writing will be furnished to all prospective applicants who have requested 
the RFA and/or submitted a LETTER OF INTENT, and will be placed on the 
NIDDK web site.

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. This version of the PHS 398 is 
available in an interactive, searchable PDF format. 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.

Application Requirements

Applicants must describe plans to accommodate the stated program 
requirements, criteria, and staff involvement.  Applicants must address 
points discussed in the SPECIAL REQUIREMENTS section of this RFA.

SPECIAL INSTRUCTIONS TO APPLICANTS

General Application Format Instructions

The form PHS 398 should be modified as follows. Biosketches and "Other 
Support" pages should be included for all personnel. The number of pages 
allowed for the "Research Plan" is increased from 25 to 40 pages.  Budget 
pages, budget justifications, material transfer agreements, and letters 
from collaborators and consultants and their biosketches are not included 
in this limit.

As described in detail above in RESEARCH OBJECTIVES (Objectives and 
Scope), applicants should divide the "Research Plan" into six sections: 
Characterization and Definition of Cell Populations, mRNA Expression 
Profile, Histology and Functional Genomics, Database, Research Tool 
Distribution, and Outreach.  In all sections, the roles and expertise of 
all key personnel, collaborators, and consultants who are associated with 
this part of the application should be well documented.

Applicants must provide methods to maintain GAP records, establish, 
standardize, document, and distribute protocols, and provide for quality 
control and budgetary oversight.  Applicants must also provide methods to 
establish priorities among the proposed projects and to oversee the daily 
operation of Units.

The proposal should include the description of the internal advisory board 
consisting of the Principal and co-Investigators and other important 
personnel that will oversee the daily operation of the Unit.  Applicants 
should describe how the GAP will fit into, augment, and be supported by 
the parent institution and plan for designating an alternate or 
replacement Principal Investigator should it become necessary.

In this part of the "Research Plan," applicants must include specific 
plans for responding to the "SPECIAL REQUIREMENTS" section.  Applicants 
should state their willingness to collaborate and share data freely with 
the other GAPs and the larger research community. Applicants must include 
a data sharing plan and copies of all Material Transfer Agreements used by 
all institutions involved in the application. Applicants are encouraged to 
use the NIH Simple Letter of Agreement to transfer materials, available at 
http://www.ott.nih.gov/policy/rt_guide_final.html#guide. 

Applicants should discuss their willingness to serve on the Steering 
Committee and other Consortium committees and should state their 
willingness to follow the common protocols that will be developed by the 
Steering Committee.  Applicants must state their willingness to plan and 
attend workshops and symposia.  Applicants should also describe how they 
will comply with the involvement of NIH Program Scientists and fulfill the 
responsibilities of Consortium components to work together cooperatively. 
Applicants should describe their experience with, and capability for, 
Internet-based communication and ideas for facilitating electronic 
communication and other interactions among the GAPs, NIH, and the larger 
research community.

Budget Instructions 

Applicants should complete the budget information as directed in the PHS 
398 application form.

Applicants who have additional funds to support (‘leverage’) the 
application should indicate the source of funds (institutional, R01, P01, 
P30, etc.) that permit them to accomplish the project goals. Subcontract 
budgets should be a separate page, and the subcontract indirect costs 
should be calculated and listed in the usual place as part of the direct 
costs of the budget. However, only direct costs associated with each 
subcontract will count toward the direct costs cap of $750,000 on the 
budget for the first year.

Applicants must budget for travel and per diem expenses for participation 
in the Steering Committee, subcommittees, workshops, and symposia. 
Applicants should budget for seven individual trips to the Bethesda, MD 
area each year.

SUBMISSION INSTRUCTIONS

The RFA label available in the PHS 398 (rev. 5/2001) application form must 
be affixed to the bottom of the face page of the application.  Type the 
RFA number (DK-02-018) on the label.  Failure to use this label could 
result in delayed processing of the application such that it may not reach 
the review committee in time for review.  In addition, the RFA title and 
number must be typed on line 2 of the face page of the application form 
and the YES box must be marked. The RFA label is also available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
 
Submit a signed, typewritten original of the application, including the 
Checklist, and three 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)

At time of submission, two additional copies of the application must be 
sent to:

Francisco O. Calvo, Ph.D.
Chief, Review Branch
Division of Extramural Activities, NIDDK
6707 Democracy Blvd.
Room 752, MSC 5452
Bethesda, MD  20892-5452 (Courier use ZIP 20817)
Telephone:  (301) 594-8885
FAX:  (301) 480-3505
Email:  CalvoF@extra.niddk.nih.gov

Applications must be received by March 15, 2002.  If an application is 
received after that date, it will be returned to the applicant without 
review.  

The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application.  
The CSR will not accept any application that is essentially the same as 
one already reviewed.  This does not preclude the submission of 
substantial revisions of applications previously reviewed, but such 
applications must include an Introduction addressing the previous 
critique.

REVIEW CONSIDERATIONS

General Considerations

Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by the NIDDK.  Incomplete and/or non-responsive 
applications will be returned to the applicant without further 
consideration.

Applications that are complete and responsive to the RFA will be evaluated 
for scientific and technical merit by an appropriate peer review group 
convened by the NIDDK in accordance with the review criteria stated below.  
As part of the initial merit review, a process will be used by the initial 
review group in which only those applications deemed to have the highest 
scientific merit, generally the top half of the applications under review, 
will be discussed, assigned a priority score, and receive a second level 
review by the National Diabetes and Digestive and Kidney Diseases Advisory 
Council. However, all applications will receive a written critique.

All applications will be judged on the basis of the scientific merit of 
the proposed project and the documented ability of the investigators to 
meet the RESEARCH OBJECTIVES of the RFA. Although the technical merit of 
the proposed protocol is important, it will not be the sole criterion for 
evaluation of a study. Other factors considered to be important for review 
include demonstrated expertise in HSC and progenitor cell biology, a 
multi-disciplinary team of collaborators, substantial interactions among 
collaborating researchers, demonstration of appropriate facilities and 
resources, and willingness to share data and reagents freely.

Review Criteria

Applicants are encouraged to submit and describe their own ideas about how 
best to meet the goals of the cooperative study and their specific 
protocols, and they are expected to address issues identified under 
“SPECIAL REQUIREMENTS,” ”TERMS AND CONDITIONS OF AWARD” and ”SPECIAL 
INSTRUCTIONS” sections of the RFA. The peer review group will assess the 
scientific merit of the applications and related factors using the 
following criteria:

Significance. The application should address the problem outlined in the 
RFA.  The application should demonstrate how the study would advance 
scientific and/or medical knowledge. Do the cell types chosen for 
expression profiling address important needs of the larger research 
community? What is the immediacy of the research opportunity?

Innovation. Does the project employ novel concepts, approaches or method? 
Is the project original and innovative? Does the project challenge 
existing paradigms or develop new methodologies or technologies? Will the 
approaches advance the field of hematopoietic cell development?

Approach. Are the conceptual framework, design, methods, and analyses 
adequately developed and appropriate to the aims of the project? Does the 
applicant acknowledge potential problem areas and consider alternative 
tactics? 

Investigators. Are the principal investigator and his/her collaborators 
appropriately trained and well suited to carry out this work? To what 
extent do these investigators have the necessary complementary skills? 
Have collaborations been established or consultants identified to provide 
the appropriate depth and breadth of scientific expertise required for the 
project? Will this team of investigators contribute unique skills to the 
overall Consortium? There should be evidence of prior experience in 
working collaboratively to carry out a standard protocol as well as 
evidence of willingness to work cooperatively on the Steering Committee to 
develop and follow a unified protocol.

Environment. Are the facilities for gene expression profiling, functional 
genomics, and bioinformatics appropriate to support the endeavor? 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 and incorporate the best use 
of collaborative arrangements? Is there evidence of institutional support?

Additional Considerations

Adequacy of plans for effective interaction and coordination among GAP 
components and the NIDDK: Are the proposed plans to share data and tools 
adequate? Do the investigators state their willingness to collaborate 
extensively and share information fully? Are the Material Transfer 
Agreements straightforward? Do the investigators state their willingness 
to abide by the priorities and policies agreed upon by the Steering 
Committee? Have the applicants proposed sound strategies for communication 
among themselves, with the other GAPs and with the NIH?

Reasonableness of the proposed budget and duration appropriate in relation 
to the proposed research:  Does it indicate that the applicants understand 
the requirements of managing this sort of high-throughput genomics 
enterprise? 

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, protection and retention of human subjects also 
will be evaluated, as will the safety of the research environment.  

Schedule

Letter of Intent Receipt Date:    February 15,2002
Application Receipt Date:         March 15, 2002
Peer Review Date:                 July 2002
Council Review:                   September 2002
Earliest Anticipated Start Date:  September 30, 2002

AWARD CRITERIA

Applications recommended by the NIDDK Advisory Council will be considered 
for award based upon (a) scientific and technical merit, (b) the 
importance of the proposed research in HSC lineage genomics, (c) the 
degree of originality and innovation in project design, (d) the creativity 
of the approaches and technologies for the development of reagents, 
assays, animal models and other research tools, (e) the likelihood for 
substantial contribution by the applicants to a successful collaborative 
GAP program, (f) demonstrated expertise to manage, design and coordinate 
multicenter research studies, and evidence for willingness to work 
cooperatively, (g) the quality and availability of research infrastructure 
and resources, (h) program balance, including in this instance, sufficient 
compatibility of features to make a successful collaborative program a 
reasonable likelihood, and (i) the availability of funds.

INQUIRIES

Inquiries concerning this RFA are encouraged.  The opportunity to clarify 
any issues or answer questions from potential applicants is welcomed.

Direct inquiries regarding programmatic issues to:

David G. Badman, Ph.D.
Hematology Program Director
National Institute of Diabetes and Digestive and Kidney Diseases
2 Democracy Plaza, Room 621 MSC 5458
6707 Democracy Blvd.
Bethesda, MD  20892-5458
Telephone:  (301) 594-7717
FAX:  (301) 480-3510
Email:  db70f@nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Aretina Perry-Jones
Grants Management Branch
National Institute of Diabetes and Digestive and Kidney Diseases
2 Democracy Plaza, Room 716 MSC 5456
6707 Democracy Blvd.
Bethesda, MD  20892-5456
Telephone:  (301) 594-8862
FAX:  (301) 480-3504
Email:  perrya@extra.niddk.nih.gov 

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 Request for 
Application (RFA), Adult Hematopoietic Stem Cell Genome Anatomy Projects, 
is related to the priority areas of cancer, kidney disease, and other 
chronic diseases in children and adults. 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. 93.847.  Awards are 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 NIH grants policies and Federal 
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.  
This program is not subject to the intergovernmental review requirements 
of Executive Order 12372 or Health Systems Agency review.

The PHS strongly encourages all grant and contract recipients to provide a 
smoke-free workplace and promote the non-use of all tobacco products.  In 
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits 
smoking in certain facilities (or in some cases, any 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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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