This Program Announcement expires on June 2, 2004, unless reissued.

CENTERS OF EXCELLENCE IN GENOMIC SCIENCE (Modified and reissued, see PAR-05-163)
                                         (supercedes PAR-00-101)

Release Date:  November 27, 2001

PA NUMBER:  PAR-02-021

National Human Genome Research Institute
 (http://www.nhgri.nih.gov/)
National Institute of Mental Health
 (http://www.nimh.nih.gov/)

Letter of Intent Receipt Dates:
	For Exploratory Grants (P20):  January 1, May 1, September 1
For Specialized Center (P50):  April 1
Application Receipt Dates:
	For Exploratory Grants (P20):  February 1, June 1, October 1
	For Specialized Center (P50):  June 1

PURPOSE

The National Human Genome Research Institute (NHGRI) and National Institute 
of Mental Health (NIMH) are issuing this revised Program Announcement to 
modify and clarify a number of issues related to this Centers of Excellence 
in Genomic Science (CEGS) program.  The CEGS program establishes new academic 
Centers for advanced genome research, using the P50 Specialized Center 
mechanism.  Each CEGS grant supports a multi-investigator, interdisciplinary 
team to develop innovative genomic approaches to address a particular 
biological problem.  A CEGS project will address a critical issue in genomic 
science, proposing a solution that would be a very substantial advance.  
Thus, the research conducted at these Centers will entail substantial risk, 
balanced by outstanding scientific and management plans and very high 
potential payoff.  A CEGS will focus on the development of novel 
technological or computational methods for the production or analysis of 
comprehensive data sets, or on a particular genome-scale biological problem, 
or on other ways to develop and use genomic approaches for understanding 
biological systems.  Exploiting its outstanding scientific plan and team, 
each CEGS will nurture genomic science at its institution by facilitating the 
interaction of investigators from different disciplines and by providing 
training of new investigators, expanding the pool of professional genomics 
scientists and engineers.

The formation of new groups of investigators to conduct genomic research is 
particularly encouraged.  As some newly formed groups may require substantial 
time and support for development and planning before being in a position to 
submit a high quality Center grant application, a CEGS Planning Grant (P20) 
is offered to facilitate this planning.

RESEARCH OBJECTIVES

Background

The NIH, along with several other federal, private, and international 
organizations, is currently engaged in a multi-year research program called 
the Human Genome Project (HGP).  Most of the initial goals of the HGP, 
including genetic and physical maps of the mouse and human, and the DNA 
sequences of E. coli, S. cerevisiae, C. elegans, and D. melanogaster have 
been realized.  Others will be met imminently, including the complete human 
sequence.  As of November 2001, a "working draft" of the human sequence had 
been published and more than one-half of the human sequence has been finished 
and deposited in the public sequence databases.  The complete, high quality 
finished human sequence will be available no later than 2003.  The sequencing 
of the mouse genome has reached 95% coverage.  By December 2001, 5-6X 
coverage of the genome (C57BL/6 strain) will be in the public domain and an 
assembly will be generated shortly thereafter.  The finished, high quality 
sequence will be completed no later than 2005.  As for the sequencing of the 
rat genome, coverage of greater than 1X was available as of October 2001, and 
3-4X coverage is expected by 2002.

The HGP has been characterized by a focus on efficient data production, the 
development of new technologies, and large, comprehensive genomic data sets 
such as genomic maps and complete DNA sequences.  Once the DNA sequence of an 
organism becomes available, many new avenues to studying its biology are 
opened.  However, new and improved research tools, approaches, and 
capabilities are needed to discover and exploit the vast amount of biological 
information in complete genomic DNA sequences.  In 1998, a set of new goals 
was adopted for the U.S. Human Genome Project (see Goals at 
http://www.nhgri.nih.gov/98plan/).  In addition to completing the human and 
mouse maps and sequences, the aim of the HGP was extended to developing some 
of the new data sets and technological approaches that will be necessary to 
understand and use genomic DNA sequence.  

The purpose of this solicitation is to stimulate the development of such new 
approaches, which are likely to involve computational, instrumental, 
biochemical, genetic, and analytical technologies.  These approaches are 
likely to require the expertise of teams of investigators from different 
fields as well as substantial infrastructure.

The CEGS program is designed to augment NHGRI's and NIMH's grants programs.  
For example, previous NHGRI solicitations have supported the development of 
large data sets, such as genetic maps, physical maps, or DNA sequences, to 
meet the quantitative, resource generation goals of the HGP.  While such 
programs continue, this new program is intended to provide support for novel 
basic genomics research projects.  These new Centers will explore ways to 
conduct biological research at a genomic scale, or will develop new methods, 
approaches, tools, or technologies to make possible novel analyses of 
biological questions from a genomic perspective.  Some projects may result in 
new analyses of existing data sets.  Other projects may result in 
technologies and methods that provide the ability to collect, analyze, and 
present effectively new types of genomic data sets.

NHGRI and NIMH are committed to continuing to support basic genomic research 
through investigator-initiated, single-laboratory project grants, using the 
R01, R21, and other appropriate grant mechanisms, under existing and future 
programs.  However, the resources needed to conduct the multi-faceted, multi-
disciplinary projects that may be required to achieve significant advances in 
these complex problems are sometimes beyond the scope of the typical R01 
grant.  Therefore, the CEGS program presents an opportunity for applicants to 
assemble the teams of investigators from diverse disciplines that will be 
required to approach biological problems using genomics tools in ways that 
are not possible today.  High priority will be given to projects that 
integrate multi-investigator, multi-disciplinary approaches to a focused 
scientific problem, especially those that can meld computational and 
experimental approaches.

Scope of Research

A CEGS will develop new approaches that will ultimately foster the 
integration of genomics with biomedical research.  It must investigate new 
approaches to studying a biological problem, using genomic-scale 
(comprehensive) methods, or develop new concepts, methods, technologies, or 
ways to analyze data, to advance the state of the art in applying genomic 
approaches to biological studies.  It must be tightly focused on a single 
biological problem or on an approach to solving biological problems.

The research plan for a CEGS must propose a very high level of innovation.  
The product of CEGS research is expected to dramatically enhance the 
biomedical research community's capabilities for conducting comprehensive, 
cost-effective, high throughput biomedical studies related to the DNA 
sequence and sequence products of organisms, with particular focus on human 
biology and disease.  Proposing to change the way genomic science is done in 
the future entails a substantial level of risk, because the research will by 
definition not be incremental.  To balance this risk, the application will 
present a well developed scientific and management plan to achieve a high 
pay-off result.  Collaborations to develop genomic approaches require 
proficiency in several disciplines; each CEGS will engage the expertise of a 
multi-disciplinary team, drawing from specialists in a wide range of fields 
such as biology, genetics, clinical medicine, physical sciences, mathematics, 
computer science, and engineering, as appropriate for the project.  
Applications that employ state-of-the-art science that fill in knowledge but 
do not break new ground are unresponsive to this program.

The U.S. HGP goals for 1998-2003 (Science, Vol. 282, pp. 682-689, 23 Oct. 
1998, see http://www.nhgri.nih.gov/98plan/) articulated several areas of 
genomics for which substantial research opportunities exist.  The more recent 
publication of the Biomedical Information Science and Technology Initiative 
(BISTI) (http://www.nih.gov/welcome/director/060399.htm) lays out additional 
challenges, many of which are complementary to those of the HGP.  The 
following excerpts from these reports exemplify the challenges and 
opportunities that lie ahead:

o  Sequencing Technology: "In the future, de novo sequencing of additional 
genomes, comparative sequencing of closely related genomes, and sequencing to 
assess variation within genomes will become increasingly indispensable tools 
for biological and medical research....[R]esearch must be supported on new 
technologies that will make even higher throughput DNA sequencing efficient, 
accurate, and cost-effective, thus providing the foundation for other 
advanced genomic analysis tools." (HGP goals)

o  Human Genome Sequence Variation: "Natural sequence variation is a 
fundamental property of all genomes....Basic information about the types, 
frequencies, and distribution of polymorphisms in the human genome and in 
human populations is critical for progress in human genetics. Better high-
throughput methods for using such information in the study of human disease 
are also needed." (HGP goals)

o  Technology for Functional Genomics: "The availability of entire genome 
sequences is enabling a new approach to biology often called functional 
genomics - the interpretation of the function of DNA sequence on a genomic 
scale....Many genes and other functional elements of the genome are 
discovered only when the full DNA sequence is known....However, knowing the 
structure of a gene or other element is only part of the answer. The next 
step is to elucidate function, which results from the interaction of genomes 
with their environment....Large-scale characterization of the gene 
transcripts and their protein products underpins functional 
analysis....Improved technologies are [also] needed for global approaches to 
the study of non-protein-coding sequences...." (HGP goals)

o  Comparative Genomics: "Because all organisms are related through a common 
evolutionary tree, the study of one organism can provide valuable information 
about others. Much of the power of molecular genetics arises from the ability 
to isolate and understand genes from one species based on knowledge about 
related genes in another species. Comparisons between genomes...provide 
insight into the universality of biologic mechanisms and....into the details 
of gene structure and function." (HGP goals)

o  Bioinformatics and Computational Biology: "Bioinformatics support is 
essential to the implementation of genome projects and for public access to 
their output....Collection, analysis, annotation, and storage of the ever 
increasing amounts of mapping, sequencing, and expression data in publicly 
accessible, user-friendly databases is critical to the project's success. In 
addition, the community needs computational methods that will allow 
scientists to extract, view, annotate, and analyze genomic information 
efficiently." (HGP goals)

"To make optimal use of information technology, biomedical researchers need, 
first of all, the expertise to marry information technology to biology in a 
productive way. New hardware and software will be needed, together with 
deepened support and collaboration from experts in allied fields. Inevitably, 
those needs will grow as biology moves increasingly from a bench-based to a 
computer-based science, as models replace some experiments and complement 
others, as lone researchers are supplemented by interdisciplinary teams. The 
overarching need is for an intellectual fusion of biomedicine and information 
technology." (BISTI goals)

"The information that biomedical researchers are amassing in profuse 
quantities today...creates enormous digital repositories of information. The 
scale of those databases swamps all the information collected before....In 
order to be useful, the data must be indexed and stored, and the challenges 
for data analysis and abstraction are formidable." (BISTI goals)

The passages quoted above from the U.S. HGP five-year plan and the BISTI 
report are intended to convey the kinds of subjects that may be appropriate 
under this Centers program.  This PA does not provide a list of examples of 
possible Center themes because of the desire not to limit applicants' 
imaginations and to solicit truly new ideas for genomic approaches to 
biological problems, as they pertain to the goals discussed above.  
Investigators who wish to propose developing such novel approaches are 
strongly encouraged to discuss their ideas with program staff prior to 
submitting an application, to ensure that applications will be responsive to 
the CEGS program.

Biomedical research has entered an era in which the solutions to many 
important problems requires the collection and analysis of large data sets, 
such as an entire genome, an entire set of expressed RNAs or proteins, an 
entire gene family from a large number of species, the variation among 
individuals for a genomic region of substantial size, or a class of gene 
regulatory or chromatin organizational elements.  Therefore, the unifying 
theme for this program will be that the Centers will address important 
biological problems on a "genomic scale."  In this context, the term 
"genomics" is not limited to studies directly related to DNA sequence, but 
instead encompasses global, comprehensive, high-throughput, cost-effective 
approaches to studying biological systems, including for example DNA, RNA, 
proteins, metabolites, and regulatory and biochemical pathways and networks.  
The genomic approaches and technologies that are proposed to be developed 
under CEGS support should be applicable to a wide variety of cell types or 
organisms, and usable in a global, high-throughput, cost-effective manner.  
Methods and concepts that are applicable only to a particular genetic locus,  
disease, or organ system will not be supported under this program.  Model 
systems, such as a limited number of gene families, regulatory networks, or 
pathways, may be used to develop the genomic approach, as long as the 
approach is scalable and broadly applicable.  The grant application must 
clearly justify how the model study will be expandable beyond the particular 
model(s) used in the developmental research, to ultimately support global 
analyses.  For example, if a particular pathway is being modeled, the 
application must explain how the modeling algorithms will be extended to 
other pathways.  To the extent that cost-effective, global approaches can be 
developed and also applied within the context of the CEGS budget, such 
application of the new approach is acceptable.  However, the budget limits 
under this PA may preclude both developing and globally applying the genomic 
approach that is the subject of the research.  

NIMH is especially interested in novel genomic approaches that have high 
potential for accelerating our understanding of the genetic basis of the 
nervous system and mental disorders.  Thus, these systems may provide 
appropriate models for developing the genomic approach, as described above, 
and similarly, CEGS project outcomes are generally expected to advance these 
goals because of their broad applicability.
   
Cost and data quality are central issues in the development and application 
of genomic approaches.  Therefore each CEGS must address these factors as it 
develops its grant application and implements those plans under CEGS support.  
These cost and quality concerns must be addressed both in terms of any 
utilization of conventional technologies for the collection of trial data 
sets within the CEGS research plan (if such data collection is required), and 
of the manner in which novel technologies and concepts generated by the CEGS 
would be applied in the future.  The cost of collecting global data sets is 
often very high; therefore, a CEGS application to very significantly reduce 
the cost of collecting a data set that, today, can be collected only at great 
expense, could be substantially enabling to the genomics community, and is 
therefore considered responsive to this PA.

It is anticipated that a CEGS may employ large amounts of data to accomplish 
its goals.  However, the application of genomic technologies for data 
production per se is not the purpose of a CEGS, and the CEGS program is not 
intended primarily to build infrastructure for the application of current 
genomics technologies.  Applicants may use data sets collected under other 
funding, if the CEGS project purpose is to develop novel, integrated analyses 
that extend the interpretation and utility of those data.  Decisions by NIH 
to embark on the large-scale implementation of any new tools developed by a 
CEGS to generate large data sets will require careful consideration, with 
advice from the scientific community.

Leveraging of genomic resources:  Preference will be given to the development 
of genomic methods for eukaryotes where genome sequence is available.  
Methods development or pilot studies using other systems (e.g., eukaryotes 
whose genomes have not been sequenced, or prokaryotes for which the genomic 
sequence is known) will be considered with adequate justification; direct 
applicability of methods and concepts developed in such a project to the 
analysis of eukaryotic genomes must be evident.  Where appropriate, 
integration with other NIH genomics initiatives (e.g., NHLBI genomics program 
[http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-99-024.html], full-
length cDNA [http://mgc.nci.nih.gov/], and SNPs 
[http://www.nhgri.nih.gov/About_NHGRI/Der/SNPawardees.htm]) will be 
considered advantageous. 

Training Objective 

Each CEGS application is required to have a training component that leverages 
the strengths of the Center and its investigators to train the next 
generation of interdisciplinary scientists who will bring creative approaches 
to studying biological problems through a genomic approach.  There is a 
widely recognized shortage of investigators who have the interdisciplinary 
skills needed to conduct most effectively the types of genome-scale research 
described in this PA.

"The HGP has created the need for new kinds of scientific specialists who can 
be creative at the interface of biology and other disciplines, such as 
computer science, engineering, mathematics, physics, chemistry, and the 
social sciences. As the popularity of genomic research increases, the demand 
for these specialists greatly exceeds the supply. In the past, the genome 
project has benefited immensely from the talents of non-biological 
scientists, and their participation in the future is likely to be even more 
crucial. There is an urgent need to train more scientists in 
interdisciplinary areas that can contribute to genomics. Programs must be 
developed that will encourage training of both biological and non-biological 
scientists for careers in genomics....[A] stable academic environment for 
genomic science must be created so that innovative research can be nurtured 
and training of new individuals can be assured." (HGP goals) 

"Strong action by the NIH is required because the existing biomedical 
research and teaching structures of the universities and research 
institutions of this country inadequately value interdisciplinary efforts 
generally, and computation in particular. Few grant programs and fewer 
academic departments foster the kind of interdisciplinary work required to 
meet biomedical challenges, let alone educate students about them. National 
Programs specifically would include formal and informal instruction from the 
undergraduate through post-graduate levels, and incorporate a range of 
opportunities for scholars and researchers to participate." (BISTI goals)

One reason for the lack of adequately qualified personnel is that there are 
too few appropriate environments available to support this kind of training. 
The CEGS program is intended to help to alleviate this shortage by supporting 
the development of Centers that can serve as academic foci for genomics, and 
thereby to increase the cadre of investigators qualified to participate in 
the development of new genomics approaches to biomedical research.  

To maximize the impact of these new Centers, they should integrate the 
training of new investigators and broaden the training of established 
investigators.  This might include plans to recruit into genomics 
investigators already trained and accomplished in other fields of research 
and engineering.  Graduate students and postdoctoral fellows, at a minimum, 
should participate in the research; however, such participation alone will be 
considered insufficient to meet the training goals of the CEGS program.  
NHGRI and NIMH expect applicants to develop creative approaches, using a 
combination of the standard training vehicles used by academic institutions 
(e.g., training grants, fellowships, seminar programs, course work) and more 
novel avenues.  This training program should take advantage of unique aspects 
of the research program, the combination of investigators' talents, and other 
unique institutional resources that underpin the CEGS, to offer innovative, 
substantive training opportunities for pre-doctoral students, post-doctoral 
fellows, and other investigators.  The CEGS will therefore become an 
additional opportunity, beyond those previously developed by NHGRI and NIMH 
(see http://www.nhgri.nih.gov/Grant_info/Funding/Training/), for expanding 
the cadre of investigators working in the field of genomics.  

NHGRI and NIMH are committed to increasing the number of individuals from 
underrepresented minority groups who have the training to pursue careers in 
genome and ELSI research.  NHGRI has conducted workshops to develop goals, 
plans and resources, to aid in the development of such training programs.  
The action plan which was developed by the staff and approved by the National 
Advisory Council for Human Genome Research in May 2001 strongly encourages 
the NHGRI staff and its grantees to work cooperatively in increasing the 
number of underrepresented minorities involved in genomics research.  This 
information is available from 
http://www.nhgri.nih.gov/Policy_and_public_affairs/Minority_Activities/minority_planning.htm

l   Genome research offers tremendous challenges and opportunities for 
improving human health and ELSI research offers the chance to explore some of 
the most profound ethical, legal and social issues of our time.  There are 
extraordinary career opportunities in genome and ELSI research that all 
should share in.  

The scope and importance of research conducted in CEGS is anticipated to 
provide an outstanding opportunity for the training of underrepresented 
minority scientists.  Moreover, the research infrastructure of CEGS 
institutions provides ideal training environments for short- and long-term 
training opportunities.  NHGRI and NIMH actively encourage all CEGS programs 
to include training of underrepresented minorities at all career levels in 
their research.  Therefore, in the context of the overall training plan, 
applicants should describe their specific plans for training of 
underrepresented minorities.  

ELSI Objective

For CEGS research projects that raise substantial ethical, legal, or social 
concerns (e.g., the study of sequence variation in specific populations), a 
component of the Center focusing on analysis of such concerns as they relate 
to the particular research proposed is strongly encouraged.  To be considered 
for funding as part of the CEGS grant, the ELSI research must be effectively 
integrated with and highly relevant to the research plan.  Current 
information on the NHGRI ELSI program is available at 
http://www.nhgri.nih.gov:80/About_NHGRI/Der/Elsi/   Please note that CEGS 
applications are not required to have an ELSI component.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic 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.  
Applications from foreign institutions and for-profit organizations will not 
be accepted; however, subcontracts to foreign institutions and for-profit 
organizations will be considered.

MECHANISM OF SUPPORT

This PA will use the National Institutes of Health (NIH) P50 Specialized 
Center and P20 Exploratory Grant mechanisms.  Responsibility for the 
planning, direction, and execution of the proposed project will be solely 
that of the applicant.

For administrative reasons all applications received in response to this 
solicitation will be initially assigned to NHGRI.  After discussions between 
the two participating NIH Institutes and after review and prior to award, the 
most programmatically relevant applications may be reassigned to NIMH.  All 
funded applications, regardless of their eventual assignment, will be managed 
administratively in accordance with the goals and objectives established by 
NHGRI for the CEGS program.

P50 Specialized Center Grants

A P50 Center grant application may request up to five years of support.  The 
length of award will be determined through the peer review and Council 
advisory processes.  Genomics is a rapidly changing field, and it is 
anticipated that most projects that can be initiated now are likely to have a 
limited lifetime during which support as a CEGS will be appropriate, either 
because the project goals will have been accomplished or the Center will have 
developed to the point that support from another source will be more 
appropriate.  Therefore, the total length of support for any P50 Center under 
this program will not exceed ten years.

In general, each CEGS will receive an administrative site visit during the 
third year of each competing cycle. The fifth year of funding will depend on 
the outcome of that administrative review, and the Principal Investigator 
(P.I.) will receive advice about the NHGRI's and NIHM's interest in accepting 
a competing renewal application to extend the initial award.  

The requested budget for a CEGS may be up to $2 million direct costs for the 
first year for continuing operations (e.g., personnel, standard laboratory 
equipment, supplies, travel and other expenses).  Future year budgets may 
exceed $2M for inflationary adjustments.  Under this cap, it is anticipated 
that the size of the awards will vary because the nature and scope of 
research programs will vary.  To accommodate collaborations that extend 
beyond single institutions, Facilities & Administrative (F&A) charges on the 
subcontracts, which are formally direct costs to the parent institution, will 
be excluded in considering the $2M operating costs limit.  Because of the 
unusual nature of these Centers, they may need to acquire specialized 
equipment.  Funds for such specialized equipment may be requested in excess 
of the $2 million operating costs limit if very well justified.  Specialized 
equipment in excess of $500,000 over the life of the grant will generally not 
be permitted.  NHGRI and NIMH anticipate establishing ten or more CEGS over 
the next few years, and therefore expect that two to four P50 awards will be 
made per year.  The actual number of awards and level of support will depend 
on receipt of a sufficient number of applications of high scientific merit 
and availability of funds.

P20 Planning Grants

A high priority under this program is the establishment of new academic 
Centers in which state-of-the-art genomics research can be conducted.  At 
some institutions, the nucleus of a well-functioning collaborative research 
group that could conduct the research described in this PA may already exist, 
and such groups will be able to submit suitable P50 applications for this 
program directly.  However, some groups of investigators may require an 
opportunity to collect preliminary data, enhance their collaborative network 
by strengthening and establishing new multi-investigator or interdisciplinary 
relationships, demonstrate effective collaborations, explore organizational 
concepts, develop courses or curricula, or refine and fully develop the 
vision of the proposed P50 CEGS project.  The Exploratory Grant (P20) 
mechanism should be used when the applicant wishes to request a period of 
planning and preliminary investigation prior to preparing a P50 Center 
application.  The planning grant application must explicitly demonstrate how 
the planning grant activities will lead to the P50 application, and describe 
in substantial detail a vision of the research to be conducted under the 
subsequent P50 grant.  The planning grant budget may request funds for 
partial salary of key investigators, travel, and some supplies and equipment. 
Planning grants will be awarded for up to three years and up to $150,000 
direct cost per year.  A planning grant is not required as a precursor to a 
P50 Center application.  Funding of a planning grant does not obligate NHGRI 
to fund a subsequent P50 Center grant.

GUIDANCE FOR APPLICANTS FOR P50 CENTER GRANTS

Innovative Genomic Approach

The applicant should identify clearly in the abstract and more fully in the 
research plan the new capabilities that are proposed to be developed, and the 
specific biological context in which those capabilities will be developed and 
studied, as a result of the establishment of the Center.  The synergies 
achieved through the establishment of multi-disciplinary teams and 
collaborations should be fully described, as these are central requirements 
for the establishment of a CEGS. 

Each of the items listed below must be addressed in clearly labeled sections 
of the application:  Management and Organization, Training Plan, ELSI 
Research Plan (if included), Data and Materials Dissemination Plan, Human 
Subjects, and Vertebrate Animals.  These sections are in addition to the 40 
page Research Plan (sections a-d; see APPLICATION PROCEDURES, below).

Management and Organization

A successful P50 grant application will include a well-integrated project 
plan.  The grant application should describe the specific administrative and 
organizational structure that will be used to support the research, and the 
synergies enabled by this structure.  CEGS projects will be multi-
disciplinary and will draw on a variety of resources.  Thus, a well thought-
out and carefully described organization will be required.  If core 
facilities or shared resources are required, these should be described, as 
should their management and service to the research projects. 

The application should explain how different components of the organization, 
including key personnel, will interact, why they are essential to 
accomplishing the overall goal of the research, and how the combined 
resources create capabilities that are more than the sum of the parts.  Very 
clear evidence that the key investigators will collaborate effectively must 
be presented in the application.  If such evidence cannot be provided, a P20 
planning grant is recommended for launching the project.  "Centers-without-
walls" are welcome under this solicitation.  However, if any component of a 
proposed Center is physically separated from the others (i.e., in a different 
department or institution), the application must address how the effects of 
that separation will be managed.  The NHGRI is not specifying a particular 
organizational structure for a CEGS, as each applicant should develop the 
structure that would best promote the proposed research.  However, note that 
the effectiveness of the proposed structure will be a criterion of the 
evaluation prior to an award and its implementation will be monitored after 
an award is made. 

The P.I. is responsible for ensuring that scientific goals are met and for 
developing and managing a decision-making structure and process that will 
allow resources to be allocated (and reallocated, as necessary) to meet those 
goals.  To be successful, projects of the complexity, both scientific and 
managerial, that participating institutes anticipate will characterize a CEGS 
require a substantial amount of the P.I.'s effort.  Therefore, the P.I. will 
be required to devote at least 30% effort to the leadership and 
implementation of the Center.

A timeline for the project should be presented.  This timeline should outline 
how the project's goals can be met within the time frame of a CEGS grant.  
The timeline will also assist the investigators, NHGRI and NIMH, and their 
advisors in evaluating progress toward the project's goals.  For those 
projects for which the investigator deems it appropriate to do so, applicants 
are encouraged to present explicit, quantitative milestones.

Training Plan

Referring to the training goals described above, this section of the 
application will describe the training plan, and how the proposed CEGS 
training component would broaden the "expert" base of genomics research 
scientists.  Training of underrepresented minority individuals, women, and 
persons with disabilities is a high priority and must be described in detail.

Data and Materials Dissemination Plan

The sharing of materials, data, methods, and software in a timely manner has 
been an essential element in the rapid progress that has been made in genome 
research.  Early in the project, the advisors to the NIH and the Department 
of Energy (DOE) genome programs encouraged more rapid sharing than had been 
practiced in most biological research  
(http://www.nhgri.nih.gov/Grant_info/Funding/Statements/data_release.html). 
This has become the standard for genome research.  In fact, attention to the 
importance of rapid and wide dissemination of research tools has expanded 
beyond the genome community.  The NIH, as a whole, is interested in ensuring 
that the information about new methods, technologies, computer software, and 
as many data developed through federally-sponsored research as possible 
becomes readily available to the research community for further research and 
development.  With the expectation that this will stimulate additional 
research and thus lead more rapidly to information and products that improve 
the health of the public, the NIH has recently issued a set of Principles and 
Guidance that address the issue of data release 
(http://www.ott.nih.gov/policy/rt_guide_final.html). 

This guidance is an integral part of the philosophy of rapid data release in 
the CEGS program for any large-scale data collection.  To the extent that 
established public databases (e.g., GenBank and dbSNP) have the capability 
for collecting and disseminating the data that would be collected under a 
CEGS grant, a plan for the rapid deposition of data into such public 
databases should be presented in the application.  If the established public 
databases cannot be used for this purpose, applicants should develop and 
propose specific plans for sharing the data generated through the grant.  
Similarly, applicants should propose specific plans to share materials, 
methods, technologies, and software generated through the grant.

The technology transfer practices and policies of the applicant institution, 
as they relate to resources anticipated to be developed through NIH support 
of the proposed project, should be described in the CEGS application.  If the 
collaborations supported under the grant will involve commercial entities, 
the effect this will have on widespread and rapid dissemination of data and 
materials produced under federal support should also be described.  It is to 
the advantage of applicants and their collaborators to have reached agreement 
as early as possible on issues related to technology transfer and data and 
materials dissemination, and to describe these plans in the application.  
Under NIH grants policy, the grantee institution cannot provide funds to 
collaborating entities until subcontracts have been negotiated.  
Additionally, peer reviewers, NHGRI and NIMH staff, and advisors will 
evaluate the adequacy of dissemination plans prior to award (see below).  
Please note that institutional sign-off on the grant application signifies 
that all relevant components of the institution, including the technology 
transfer office, have reviewed and approved the document.

The initial review group will comment on the appropriateness of the proposed 
plan for data and materials dissemination.  NHGRI and NIMH advisors and staff 
will also consider the adequacy of the dissemination plan as one of the 
criteria for award.  The proposed sharing plan, after negotiation with the 
applicant when necessary, will be made a condition of the award.  Evaluation 
of competing renewal application and annual non-competing progress reports 
will include assessment of the responsiveness to NIH guidelines of data, 
materials, methods, and software dissemination practice by the grantee.   

Human Subjects

The PHS 398 form describes the information that must be included in the 
application, section e, concerning the protection and inclusion of human 
subjects in research.  Note that a recent change in NIH policy no longer 
requires the applicant to obtain Institutional Review Board (IRB) approval 
prior to submission or review of the application.  Instead, IRB approval is 
required before an award is made.

Vertebrate Animals

The PHS 398 form describes the information that must be included in the 
application, section f, concerning the use of vertebrate animals.  Note that 
IACUC approval must be obtained before the application can be reviewed.

LETTER OF INTENT 

Prospective applicants are asked to submit a letter of intent that includes a 
descriptive title of the proposed research, the name, address, telephone 
number, and e-mail address of the principal investigator, names of other key 
personnel and, if applicable, participating institutions, and the number and 
title of this PA.  Although a letter of intent is not required, is not 
binding, and does not enter into the review of subsequent applications, the 
information that it contains allows NHGRI staff to estimate the potential 
review workload and plan the review.  Applicants planning to request $500,000 
or more in direct costs for any year must receive authorization from NHGRI 
program staff at least six weeks before submitting the application (see 
ADDITIONAL APPLICATION PROCEDURES FOR P50 CENTER GRANTS, below).

The letter of intent is to be sent by e-mail to: 

Jeffery A. Schloss, Ph.D.
Division of Extramural Research
National Human Genome Research Institute, NIH 
TEL:  (301) 496-7531
FAX:  (301) 480-2770 
Email:  jeff_schloss@nih.gov 

APPLICATION PROCEDURES (P50 AND P20)

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 application deadlines 
indicated on the first page of this PA. This version of the PHS 398 is 
available in an interactive searchable format. Beginning January 10, 2002, 
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.

The P20 grant applications will have the standard 25 page limit for Research 
Plan sections a-d.

The title and number of the PA 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 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 the time of submission, two additional copies of the application, 
including all appendices, must be sent to: 

SCIENTIFIC REVIEW BRANCH
NATIONAL HUMAN GENOME RESEARCH INSTITUTE, NIH
BLDG. 31, ROOM B2-B37 
BETHESDA, MD  20892-2032 
TEL:  (301) 402-0838 
FAX:  (301) 435-1580 

ADDITIONAL APPLICATION PROCEDURES FOR P50 CENTER GRANTS

The page limit for applications using the PHS 398 form will be expanded to 40 
pages for Items a-d of the Research Plan, for CEGS P50 applications.  In 
addition to the 40 page Research Plan, the following separate sections are to 
be included in the application, observing the stated page limits:  The 
Management and Organization Plan, Training Plan, and Data and Materials 
Dissemination Plan, combined, may not exceed 12 pages.  The ELSI plan, if 
included, may not exceed 5 pages.  

In accordance with NIH policy (NIH Guide for Grants and Contracts, October 
16, 2001, available at http://grants.nih.gov/grants/guide/notice-files/NOT-
OD-02-004.html), an applicant planning to submit a 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 MUST contact NHGRI program staff before submitting 
the application, as plans for the study are being developed, to obtain 
agreement that NHGRI will accept the application for consideration of an 
award.  Permission to submit the application must be granted at least six 
weeks before the grant application deadline.  The applicant must identify, in 
a cover letter sent with the application, the NHGRI staff member who agreed 
to accept assignment of the application. The NHGRI is not obligated to accept 
applications requesting more than $500,000 in the absence of timely staff 
agreement.

This policy requires an applicant to obtain agreement for acceptance of both 
any such application and any such subsequent amendment.  Refer to the NIH 
Guide for Grants and Contracts, October 16, 2001, available at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html
 
ADDITIONAL APPLICATION PROCEDURES FOR P20 PLANNING GRANTS

The PHS 398 form will be used with the usual page limits.  The planning 
activities to be carried out, and the justification for their necessity, 
should be described in the context of the anticipated P50 Center grant 
application.  Describe the research plan for collection of preliminary data, 
and the scientific planning that will ensue to develop the full P50 grant 
application.  Describe the activities to strengthen the interdisciplinary 
team of researchers, to develop the management structure for the P50 Center, 
and to develop the courses, curriculum, and other options that will be 
included in the training plan. 

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by CSR and for 
responsiveness by the NHGRI. Incomplete and/or unresponsive applications will 
be returned to the applicant without further consideration. Applications that 
are complete and responsive to the PA will be evaluated for scientific and 
technical merit by an appropriate peer review group, convened by the NHGRI in 
accordance with the standard NIH peer review procedures. The applications 
will receive a second-level review by the National Advisory Council for Human 
Genome Research and the National Advisory Mental Health Council, as 
appropriate. 

Review Criteria 

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health. To 
ensure that applications for this CEGS program are evaluated appropriately, 
the standard NIH review criteria have been adapted to be more appropriate for 
applications of the scope described in this PA. 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 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, however, for this program, a high level of 
innovation will be required of all applications.

Review Criteria for P50 Centers 

(1) Significance:  Importance of the proposed research areas and topics being 
explored, and their relevance to investigation of biomedical problems that 
can be studied using genomic approaches.  Utility to other researchers of any 
technology, research tools, software, scientific approaches, methods of 
analysis, etc. that are proposed to be developed.  Likely effect of the 
proposed research on the field, and likely usefulness to the larger 
biological community.

(2) Approach:  Quality of the scientific research plan.  Likelihood that the 
proposed research plan will achieve the aims of the proposed research and 
will substantially improve the methodological or conceptual approach to the 
problem.  Appropriateness of the proposed experimental approach, conceptual 
framework, design, methods, analyses, techniques, and technologies to the 
proposed research.  Acknowledgement of potential problems and consideration 
of alternative approaches.  For proposed multi-component Centers, the 
scientific gain from combining the research components in a Center, i.e., the 
degree of interrelatedness and synergy among the components. If any 
individual component were removed, would the ability of the CEGS to 
accomplish its overall aims be impaired?  Plans for monitoring and ensuring 
data quality and cost reduction.  Appropriateness of timeline and milestones.

(3) Management: Appropriateness and quality of the management plan, including 
the effectiveness of the management structure. Quality of the plan for 
deployment of fiscal resources, equipment and human resources to attain the 
research aims and overall CEGS goals. Organization and coordination of the 
personnel. Quality of the plans for making critical decisions or choices 
about overall research direction during the project. Where appropriate, the 
cost-effectiveness of approaches used or under development to implement the 
research plan.

(4) Innovation: Novelty or originality of approach, method, technology, 
experimental design (including presentation, organization, analysis or 
application of data), conceptual framework, or the insight provided into a 
genomic approach to a biological problem.

(5) Investigators: Appropriateness of the scientific training, background, 
and expertise of the Principal Investigator and key personnel to achieving 
the specific aims and overall goals of the proposed research. Contribution 
that the individual and combined scientific expertise of the key personnel 
will make to the achievement of the overall goals of the proposed research. 
Adequacy of the P.I.'s ability to lead and coordinate the activities, and 
develop and implement the management plan, as required for the project's 
success. Adequacy of the level of effort of key personnel.  Evidence of 
effective collaboration among key personnel.  Formulation of a multi- or 
inter-disciplinary team that brings novel capabilities to the research 
program. 

(6) Environment: Adequacy of the scientific environment and resources 
available, including space, equipment, services, infrastructure, and 
facilities. Degree to which the proposed research plan, experiments, or 
organization take advantage of unique features of the scientific environment. 
Degree of institutional commitment, including any needed expansion of 
facilities, improvement of infrastructure, and relief from other academic 
duties where necessary. Environment for training or educational activities.

(7) Data release and distribution of research tools: Adequacy of plans for 
dissemination to the scientific community of research tools or research 
resources (e.g., data sets, computer software, mutant stocks, DNA libraries), 
methods, and technologies that are proposed to be developed. 

(8) Training: Quality of the proposed training plan and its likely 
effectiveness in producing well-trained researchers who can develop new 
genomics approaches and apply them to biological problems. Plans to develop 
new training opportunities and to integrate them with other on-going or 
planned training. Plans to achieve effective training of underrepresented 
minorities will receive particular attention.

(9) ELSI:  If plans include an ELSI project, quality of the research plans 
for the proposed ELSI project, its ability to leverage the scientific 
resources of the project, and its effective integration into the research 
activities of the CEGS.

Review Criteria for P20 Planning Grants

(1) Significance: Importance of the proposed research areas and topics being 
explored, and their relevance to elucidating a biological problem, 
particularly one that is amenable to genomic approaches. Effect of the 
proposed areas of research on the field, and the likely impact on the larger 
biological community. 

(2) Approach: Quality of the scientific research plan. Likelihood that the 
proposed planning grant will culminate in the ability to submit a high 
quality CEGS P50 grant application, through, for example, the development of 
on-going collaborations and generation of relevant preliminary data, and 
crystallization of research approaches.

(3) Management: Quality of the plan for acquisition, organization, and 
deployment of equipment and human resources to attain the goals of the 
exploratory research. Potential success of the proposed exploratory 
components.  Adequacy of the level of effort of key personnel. 

(4) Innovation: Novelty or originality of the research area being 
investigated or the methods to be developed.

(5) Investigators: Appropriateness of the training, background, and expertise 
of the P.I. and key personnel to achieving the specific aims and overall 
goals of the proposed research. 

(6) Environment: Adequacy of the scientific environment and resources 
available, including space, equipment, services, infrastructure, and 
facilities. Degree to which the proposed research plan, experiments, or 
organization take advantage of unique features of the scientific environment. 
Degree of institutional commitment, including any needed expansion of 
facilities, improvement of infrastructure, and relief from other academic 
duties where necessary. The environment for training and educational 
activities. 

(7) Data release and distribution of research tools: Adequacy of plan to 
develop a responsive data and tools distribution plan, taking into account 
all of the issues raised in the relevant section of this announcement.

(8) Training: Adequacy of plan to develop an effective training component. 

(9) ELSI:  If plans include an ELSI project, quality of the plans to develop 
an ELSI project that leverages the scientific resources of the project, and 
its effective integration into the research activities of the CEGS.

Additional Review Criteria for P50 and P20 Applications

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:

o  If the application proposes to involve human subjects or study human 
tissue samples, exempt or not, then the adequacy of plans to include both 
genders, minorities and their subgroups, and children as appropriate for the 
scientific goals of the research will be evaluated. 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 human subjects, animals, or 
the environment, to the extent they may be adversely affected by the project 
proposed in the application. 

AWARD CRITERIA 

Applications will compete for available funds with all other recommended 
applications received through this and other NHGRI and NIMH programs. The 
following will be considered in making funding decisions: Quality of the 
proposed project as determined by peer review; appropriateness of plans for 
sharing data, materials, methods, and technology; availability of funds; and 
programmatic balance and priority.

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 PA, Centers of 
Excellence in Genomic Science, is related to one or more of the priority 
areas. Potential applicants may obtain a copy of "Healthy People 2010" at: 
http://www.health.gov/healthypeople/.

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.

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 for NIH funding must be self-contained within specified page 
limitations. Unless otherwise specified in an NIH solicitation, internet 
addresses (URLs) should not be used to provide information necessary to the 
review because reviewers are under no obligation to view the Internet sites. 
Reviewers are cautioned that their anonymity may be compromised when they 
directly access an Internet site.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT

The Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) 
cited publicly and officially by a Federal agency in support of an action 
that has the force and effect of law (i.e., a regulation) may be accessed  
through FOIA.  It is important for applicants to understand the basic scope 
of this amendment.  NIH has provided guidance at:

http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm

Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application. In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.
 
INQUIRIES 

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

Direct inquiries regarding programmatic issues to: 

Jeffery A. Schloss, Ph.D.
Division of Extramural Research 
National Human Genome Research Institute, NIH
TEL:  (301) 496-7531 
FAX:  (301) 480-2770 
Email:  jeff_schloss@nih.gov

Direct inquiries regarding scientific issues on the application of genomic 
approaches to the nervous system and mental disorders to:

Steven O. Moldin, Ph.D.
Division of Neuroscience & Basic Behavioral Science
National Institute of Mental Health, NIH
TEL:  (301) 443-2037 
FAX:  (301) 443-9890 
E-mail:  smoldin@mail.nih.gov

Direct inquiries regarding review issues to: 

Scientific Review Branch 
National Human Genome Research Institute, NIH
TEL:  (301) 402-0838
FAX:  (301) 435-1580 
E-mail:  rp7s@nih.gov

Direct inquiries regarding fiscal matters to:

Jean Cahill 
Grants Administration Branch 
National Human Genome Research Institute, NIH
TEL:  (301) 402-0733 
FAX:  (301) 402-1951
E-mail:  jc166o@nih.gov 

Direct inquiries regarding fiscal matters for projects on the application of 
genomic approaches to the nervous system and mental disorders to:


Carol J. Robinson
Grants Management Branch
National Institute of Mental Health, NIH
TEL:  (301) 443-3858
FAX:  (301) 443-6885
E-mail:  crobinso@mail.nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance Nos. 
93.172 (NHGRI) and 93.242 (NIMH). 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 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. 


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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