PILOT PROJECTS FOR THE PROTEIN STRUCTURE INITIATIVE (STRUCTURAL GENOMICS)
Release Date: July 24, 2000
RFA: GM-00-006
National Institute of General Medical Sciences (NIGMS)
(http://www.nigms.nih.gov/)
Letter of Intent Receipt Date: November 3, 2000
Application Receipt Date: February 12, 2001
PURPOSE
The National Institute of General Medical Sciences encourages applications
for research centers that will serve as pilots to examine the best approach
for developing subsequent integrated, large-scale research networks in
structural genomics. This is part of the Institute's Protein Structure
Initiative (PSI), whose goal is the understanding of protein structural
families, structural folds, and the relationship of structure and function.
These research centers should include all the constituent tasks of structural
genomics and should test strategies for large-scale high throughput structure
determination by X-ray crystallography and/or NMR. This RFA is a reissuance
of RFA GM-99-009
(http://grants.nih.gov/grants/guide/rfa-files/RFA-GM-99-009.html).
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
Applications (RFA), Pilot Projects for the Protein Structure Initiative
(Structural Genomics), 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/.
ELIGIBILITY REQUIREMENTS
Applications may be submitted by domestic 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.
Foreign institutions are not eligible for research center grants. However,
subcontracts to foreign institutions are allowable, with sufficient
justification.
MECHANISM OF SUPPORT
This RFA will use the National Institutes of Health (NIH) P50 research center
award mechanism. Responsibility for the planning, direction, and execution
of the proposed project will be solely that of the applicant. The total
project period for an application submitted in response to this RFA may not
exceed five years. This RFA is a one-time solicitation. Future unsolicited
competing continuation applications will compete with all investigator-
initiated applications and be reviewed according to the customary peer review
procedures. The anticipated award date is September 2001.
FUNDS AVAILABLE
The NIGMS expects to consider funding up to three research centers, each
ranging in cost no greater than $3 million direct costs for the first year.
Only applications found to be responsive to this announcement and of high
scientific merit will be considered for funding. Because the nature and
scope of the research proposed may vary, it is anticipated that the size of
each award will also vary. Although the financial plans of the NIGMS provide
support for this program, awards pursuant to this RFA are contingent upon the
availability of funds and the receipt of a sufficient number of meritorious
applications. At this time, it is not known if this RFA will be reissued.
RESEARCH OBJECTIVES
Background
Following the completion of the sequence of the human genome, a crucial step
in understanding living systems is the determination of the structure and
function of the entire set of gene products. Data from the genome project
have led to comparative protein sequence analyses and numerous efforts to
develop methodologies for the identification of protein families.
Utilization of these computational analyses with structural determinations by
X-ray crystallography and NMR techniques to study protein structural families
constitutes the new field of structural genomics and is the goal of the NIGMS
Protein Structure Initiative (PSI). These studies should lead to an
understanding of structure/function relationships and the ability to obtain
structural models of all proteins identified by genomics. This project will
require the determination of a large number (perhaps 10,000) of protein
structures in a high throughput mode. Recent and anticipated technological
developments in protein structural determinations make this formidable task
feasible. The availability of comparative sequence analyses and
methodological improvements now make such a large-scale structural project
appropriate.
Three workshops sponsored by NIGMS have focussed on the practicality,
constituent tasks, goals, and planning of this project. There was general
agreement on technical feasibility due to advances in the development of high
throughput expression systems, protein purification, and sample preparation
(crystallization for X-ray crystallography and isotopic labeling for NMR).
All of these likely can be organized on the large scale required. Methods
for the structure determination of proteins have also improved significantly
in recent years. The identification of protein families and target selection
proved to be the most controversial topic and was the focus of the third
workshop. A summary of these meetings can be found on the NIGMS web site at:
http://www.nih.gov/nigms/funding/psi.html. Following the workshops and
discussions by the National Advisory General Medical Sciences Council, it was
concluded that the necessary tasks for the PSI project are feasible and that
the goal of this initiative is an important scientific endeavor. The
resulting basic set of protein structures and structure folds will be crucial
in understanding protein structure and evolution, will contribute to the
solution of the protein folding problem, and will provide insights into the
relationship of structure and function.
Objectives and Scope
The purpose of this RFA is to announce support for research centers in the
new and emerging field of structural genomics. These research centers are
intended to serve as pilots that will lead to subsequent large-scale research
networks in structural genomics and high throughput structural determination
of proteins by X-ray crystallography and NMR methods. They should contain
all of the constituent tasks of structural genomics and should demonstrate
the ability to accomplish the computational and experimental facets as an
integrated and high throughput operation. Effective plans for management and
administration of the research centers are crucial. Attention should be paid
to costs and efficiency, as well as technology development. Rapid release of
data into the public databases will be required, as described below.
Applicants should include the following components:
1) Family Classification and Target Selection: There are several schemes of
comparative protein sequence analysis for parsing genomes into protein
families and for choosing protein targets for structural genomics projects.
These have been discussed in the scientific literature and at several recent
scientific meetings and workshops (for example, see the NIGMS Structural
Genomics Targets Workshop, referenced above). Examples for targeting schemes
to choose or prioritize proteins for structural determination include: many
of the proteins of single organisms with a completed genome; putative
proteins of unknown function; protein families of known functions or medical
relevance; and clusters of orthologous groups (COGs) spanning the three
domains of life and perhaps corresponding to "ancient conserved regions."
Since no single scheme has emerged as a consensus choice, this decision is
left to applicants. Their experience and results in choosing an approach
that can ultimately be generalized are expected to be one of the outcomes of
these pilot projects. The targeting scheme should be designed to test
strategies for coverage of all proteins found in nature. Applicants are
expected to determine their own target selection schemes and to present
detailed plans and preliminary results for this stage of their structural
genomics project.
2) Generation of Protein for Biophysical Analyses: There is now considerable
experience in the generation of expression systems to produce large
quantities of most proteins in a form suitable for biophysical studies.
Applicants for the research centers should present evidence of their
capability to generate protein expression systems, to overexpress proteins,
and to purify protein samples. Emphasis should be on high throughput,
efficiency, and cost savings.
3) Sample Preparation for Structural Studies: This crucial experimental task
has seen significant progress recently. There has been greater understanding
of the basic mechanisms of crystallizations by various physical approaches.
These advances have significantly improved the ability of structural
biologists to crystallize proteins, especially for soluble globular proteins.
NMR studies will require isotopic labeling of protein samples. The
applicant's experience and plans for the preparation of samples for structure
determinations in a high throughput mode should also be presented.
Crystallization of membrane proteins and a number of other classes of
proteins are still very difficult and not yet amenable to high throughput
operations, but innovative projects in this area as part of a larger effort
are encouraged.
4) Structure Determination: With many major technical advances in recent
years, X-ray crystallography for high-resolution structure determination has
become straightforward for many protein samples. The major breakthrough has
been the almost universal use of synchrotron beamlines, which produce high
fluxes and variable wavelengths. In addition, major improvements have come
from new detectors, cryocrystallographic techniques, multiple-wavelength
anomalous diffraction techniques, and advanced computational systems for
rapid data collection, processing, and model building. New NMR methods and
higher field instruments have increased the size of proteins that can be
solved by this technique. The structure determination component should be
the nucleus of a structural genomics research center and applicants should
have considerable expertise and resources in either or both of these
techniques. The research centers should have plans for structural
determinations in a high throughput mode, with emphasis on efficiency, cost
reductions, and extensions to large-scale operation. The research centers
are expected to demonstrate their access to state-of-the-art synchrotron
and/or NMR facilities. The NIGMS is currently planning the development of
additional beamlines at several synchrotron facilities, and will likely be
able to make additional beamtime available to general users and research
centers funded by this RFA within the next few years. However, the
structural genomics research centers are expected to demonstrate their own
plans for data collection and structure determinations.
5) Analyses and Dissemination of Results: With several disparate components
that are interdependent, management and administration are crucial. In
addition to the usual administrative details, the leadership of the research
centers must have plans for directing the research, e.g., making decisions
about which proteins to study first, determining when to pursue a structure
and when to discontinue, coordination between different groups, etc. Since
the goal of this initiative is to add to the body of knowledge of protein
structure and to enable the NIGMS and scientific community to plan and
prepare for large-scale operations in structural genomics, release and
dissemination of results are crucial. In addition to the structure factors
and coordinates, this includes information on strategies for target
selections, status of research on these proteins, technological and
methodology findings, high throughput approaches, efficiency, and cost
analyses. The pilot research centers will be required to have plans for
timely deposition of coordinates and related data into the public database
and for handling intellectual property issues. They should also address
their plans for analyses of results relative to understanding protein
structure and the field of structural genomics. The NIGMS plans to hold
annual meetings at the NIH for grantees in structural genomics to discuss
their progress and results.
Summary
The purpose of this RFA is to call for applications supporting research
centers in structural genomics. These research centers are intended to
provide information to the NIH and the scientific community that will lead to
subsequent development of large-scale research networks in structural
genomics. Both computational and experimental aspects are essential, as well
as a comprehensive and integrated research plan. Emphasis should be placed
on protein structural determinations in a high throughput mode.
There are two related program announcements:
1) PA-99-116. A program for R01 and P01 grants to support research on the
development of methodology and technology underpinning the emerging field of
structural genomics. Projects related to high throughput structure
determination by X-ray crystallography and NMR, as well as those addressing
other constituent tasks of structural genomics, are relevant.
2) PA-99-117. A similar program to the above for structural genomics
methodology and technology development for Small Business Innovation
Research/Small Business Technology Transfer (SBIR/STTR) applications.
POST-AWARD MANAGEMENT
During the course of the grant period, both computational and experimental
technologies will improve, and the rate of progress and focus of work
supported by the grant may change. It is expected that the Principal
Investigator will make any necessary adjustment in scientific direction to
accommodate the expected scale-up and changing environment, keeping the NIGMS
staff informed if significant changes are made. In order to ensure that the
project remains focused on appropriate goals, incorporates new technological
advances and makes sufficient progress, scientific and programmatic visits to
the grantee will be conducted at a frequency to be negotiated with the
awardee. In addition, benchmarks for progress may be changed annually.
The NIGMS may include outside consultants in the annual progress review and
reduce or withhold funds for failure to meet milestones agreed upon by
grantees and NIH staff. A report by the NIGMS program director on each
research center's progress and any recommendations to modify funding will be
made annually to the National Advisory General Medical Sciences Council.
SPECIAL REQUIREMENTS
The NIGMS has adopted several polices that are applicable to these structural
genomics research centers. Applicants must present plans to adhere to the
policies, where appropriate.
Research Training. In most cases, the research projects envisioned at this
stage of the PSI will involve extensive data collection with limited
hypothesis-driven aspects. Therefore they may not be appropriate as research
training projects. Applicants planning to employ graduate students and/or
postdoctoral research assistants on their project should address this issue.
Intellectual property. The results of the structural genomics projects
should be freely available for use by the entire research community and,
therefore, must be released into the public domain. Applicants should
present plans related to intellectual property rights. The NIGMS will
monitor its grantees' activities with respect to patenting the structural
results and technology developments.
Data Release and Sharing of Results and Materials. Structural results,
including protein coordinates and structure factors should be deposited
promptly into the Protein Data Bank (PDB). Guidelines developed by NIH do
not permit holds on deposited coordinates
(http://grants.nih.gov/grants/guide/notice-files/not99-010.html). In
addition, dissemination of results of the structural genomics research
centers is crucial and applicants should plan on sharing findings and the
experiences at the annual meetings for structural genomics grantees and in
other appropriate forums. This includes information on strategies for target
selections, status of research on these proteins, technological and
methodology findings, high throughput approaches, efficiency, and cost
analyses. Grantees will be required to develop and maintain a public website
showing the information listed above, as well as providing it in their annual
progress report. The NIGMS is supporting the development of a database
(contact Dr. Norvell at NIGMS for updated information) to facilitate this
sharing of information and the coordination of the research projects
undertaken by the research centers. In some cases, the proteins and samples
generated by these research centers will need to be pursued by detailed
functional studies by scientists both within and outside the research centers
and beyond the scope of these awards. Thus, the research centers should have
plans both for timely deposition of coordinates and related data and for
sharing results and materials.
Management Plan. The management of a structural genomics research center
requires a significant commitment by the Principal Investigator.
Accordingly, he or she is expected to devote a substantial effort to the
project. The applicant must propose a management plan that takes into
account the changes that will occur over the 5-year term of the award.
External Scientific Advisory Committee. Each research center should have an
external advisory committee of research scientists not involved in the
consortium to provide independent assessment and advice to the Principal
Investigator and staff. This committee should be appointed by the Principal
Investigator and meet at least twice each year. In order to maximize the
pool of possible reviewers, the potential members of the advisory committee
should not be contacted or selected until after an award has been made.
Annual Meeting. Grantees in the PSI program will be expected to attend an
annual meeting at the NIH to discuss their progress and results.
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 subpopulations 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 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
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical
Research," which was published in the Federal Register of March 28, 1994 (FR
59 14508-14513) and in the NIH Guide for Grants and Contracts, Vol. 23, No.
11, March 18, 1994, and is available on the web at:
http://grants.nih.gov/grants/guide/notice-files/not94-100.html.
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS
It is the policy of NIH that children (i.e., individuals under the age of 21)
must be included in all human subjects research, conducted or supported by
the NIH, unless there are scientific and ethical reasons not to include them.
This policy applies to all initial (Type 1) applications submitted for
receipt dates after October 1, 1998.
All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines" on the Inclusion of Children as Participants in
Research Involving Human Subjects that was published in the NIH Guide for
Grants and Contracts, March 6, 1998, and is available at the following URL
address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html.
Investigators also may obtain copies of these policies from the program staff
listed under INQUIRIES. Program staff may also provide additional relevant
information concerning the policy.
URLS IN NIH GRANT APPLICATIONS OR APPENDICES
All applications and proposals for NIH funding must be self-contained within
specified page limitations. Unless otherwise specified in an NIH
solicitation, internet addresses (URLs) should not be used to provide
information necessary to the review because reviewers are under no obligation
to view the Internet sites. Reviewers are cautioned that their anonymity may
be compromised when they directly access an Internet site.
LETTER OF INTENT
Prospective applicants are asked to submit, by November 3, 2000, a letter of
intent that includes a descriptive title of the proposed research, the name,
address, and telephone number of the Principal Investigator; abstract; the
identities of other key personnel and participating institutions; and the
number and title of the RFA in response to which the application will be
submitted. 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 Institute staff to estimate the potential review
workload and to avoid conflict of interest in the review.
The letter of intent is to be sent to:
John C. Norvell, Ph.D.
Division of Cell Biology and Biophysics
National Institute of General Medical Sciences
45 Center Drive, Room 2AS.13B
Bethesda, MD 20892-6200
Telephone: (301) 594-0533
FAX: (301) 480-2004
Email: norvellj@nigms.nih.gov
APPLICATION PROCEDURES
Applications are to be submitted on the grant application form PHS 398 (rev.
4/98) and will be accepted only at the deadline of February 12, 2001.
Application kits are available at most institutional offices of sponsored
research, on the Internet at:
http://grants.nih.gov/grants/funding/phs398/phs398.html, and may be obtained
from the Division of Extramural Outreach and Information Resources, National
Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-
7910, telephone 301-435-0714, email: grantsinfo@nih.gov.
The RFA label available in the PHS 398 (rev. 4/98) application form must be
affixed to the bottom of the face page of the application. 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, ("Protein Structure Initiative," GM-00-006) must be typed
on the RFA label and on line 2 of the face page of the application form and
the YES box must be marked.
The sample RFA label available at:
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to
allow for this change. Please note this is in pdf format.
Potential applicants are strongly urged to contact the program staff listed
under INQUIRIES for guidance in the preparation of the application.
Responsibility for the planning, direction, and execution of the proposed
project will be solely that of the applicant. The total project period for
an application submitted in response to this RFA may not exceed five years.
Special application requirements
The research center should be an integrated, coordinated project, with
various interdependent subprojects that comprise structural genomics as
described above. The subprojects should be organized to be consistent with
the five components of structural genomics that were listed above in the
section "Research Objectives." They must be fully described and justified.
Collaborations and consortia are encouraged. In such collaborations, the
respective contributions should be well integrated into the design of the
application. The application should have a face page; abstract; project
summary; plans for administrative management; plans for project management
with annual milestones and evaluations; subproject descriptions; consolidated
budget; subproject budgets; key personnel listing; biographical sketches;
investigators' other support; institutional support, resources and
facilities; letters of collaboration; plans for sharing results and
materials; plans for handling intellectual property issues; etc. An overview
section should be prepared that includes an overall description which defines
the scope and objectives. The budget should be no greater than $3 million
direct costs (facilities and administrative (F&A) costs on subprojects are
not included in this cap) for the first year, with annual cost-of-living
increases in subsequent years. It should be fully justified and should
include funds for attending the annual meeting. The page limit for the
research plan (including specific aims, background and significance,
preliminary studies, and research design and methods) is increased to 60
pages total.
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 and any
appendix material must be sent to:
Helen R. Sunshine, Ph.D., Chief
Office of Scientific Review
National Institute of General Medical Sciences
Building 45, Room Number 1As.13
National Institutes of Health
Bethesda, MD 20892
Applications must be received by February 12, 2001. 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 already reviewed, but such applications
must include an introduction addressing the previous critique.
REVIEW CONSIDERATIONS
Upon receipt, applications will be reviewed for completeness by CSR and for
responsiveness to the RFA by the NIGMS program staff. Incomplete and/or
nonresponsive applications will be returned to the applicant without further
consideration. Those applications that are complete and responsive will be
evaluated in accordance with the criteria stated below for
scientific/technical merit by an appropriate peer review group convened by
the NIGMS. Site visits or applicant interviews may or may not be performed
as part of the initial review. Applicants should not assume they will occur
and therefore must present a complete and well-justified written proposal.
As part of the initial merit review, all applications will receive a written
critique and may undergo a process in which only those applications deemed to
have the highest scientific merit will be discussed, assigned a priority
score, and receive a second level review by the National Advisory General
Medical Sciences Council.
Review Criteria
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health. In
the written comments reviewers will be asked to discuss the following aspects
of the application in order to judge the likelihood that the proposed
research will have a substantial impact on the pursuit of these goals. Each
of these criteria will be addressed and considered in assigning the overall
score, weighting them as appropriate for each application.
1. Significance: Will this research project make an important contribution
to the field of structural genomics? If the aims of the application are
achieved, how will scientific knowledge be advanced? What will be the effect
of these studies on the concepts or methods that drive this field? What is
the likelihood that the research center will be able to evolve into a
successful large-scale high throughput structure determination research
network?
2. Approach: Are the conceptual framework, design, methods, and analyses
adequately developed, well integrated, and appropriate to the aims of the
project? Does the applicant acknowledge potential problem areas and consider
alternative tactics? Is the management and administrative framework
adequate? Are the milestones and plans for evaluations appropriate?
3. Innovation: Does the project employ novel concepts, approaches or
methods? Are the aims original and innovative? Does the project challenge
existing paradigms or develop new methodologies or technologies? How
exportable are these strategies and technologies? Is there a plan for
incorporating new technologies at reasonable costs?
4. Investigator: Is the investigator appropriately trained and well suited
to carry out this work? Is the work proposed appropriate to the experience
level of the Principal Investigator and other researchers? Does the
Principal Investigator have the appropriate management and administrative
skills?
5. Environment: Does the scientific environment in which the work will be
done contribute to the probability of success? Do the proposed research
centers take advantage of unique features of the scientific environment or
employ useful collaborative arrangements? Is there adequate institutional
support?
In addition to the above criteria, in accordance with NIH policy, all
applications will also be reviewed with respect to the following:
o Plans for protein family classification and target selection, including
plans for testing this strategy and its applicability to subsequent large-
scale research networks.
o Plans and previously demonstrated success in increasing throughput and
decreasing costs.
o Plans for handling intellectual property issues, for sharing results and
materials generated by this research, and for prompt placement of data in the
public domain, including deposition of coordinates in the Protein Data Bank.
o The reasonableness of the proposed budget in relation to the proposed
research, and
o The adequacy of the proposed protection for humans, animals or the
environment, to the extent they may be adversely affected by the project
proposed in the application.
Schedule
Letter of Intent Receipt Date: November 3, 2000
Application Receipt Date: February 12, 2001
Peer Review Date: June 2001
Council Review: September/October 2001
Earliest Anticipated Start Date: September 2001
AWARD CRITERIA
Applications will compete for available funds with all other approved
applications assigned to the NIGMS. Awards will be made in September 2001.
The following will be considered in making funding decisions:
o quality of the proposed project as determined by peer review;
o program priority of research in this area and other areas of
Institute interest;
o plans for rapid dissemination of the results and information on
technological developments, including rapid deposition and release of all
protein coordinates and structure factors into the PDB, i.e., holds on
release are not permitted;
o overall contribution of the project to knowledge and experience required
to meet the long range goals of the structural genomics project; and
o availability of funds.
INQUIRIES
Inquiries are encouraged. The opportunity to clarify any issues or questions
from potential applicants is welcome.
Direct inquiries regarding programmatic issues to:
John C. Norvell, Ph.D.
Division of Cell Biology and Biophysics
National Institute of General Medical Sciences
45 Center Drive, Room 2AS.13B
Bethesda, MD 20892-6200
Telephone: (301) 594-0533
FAX: (301) 480-2004
Email: norvellj@nigms.nih.gov
Direct inquiries regarding fiscal matters to:
Ms. Grace Tuanmu
Grants Management Office
National Institute of General Medical Sciences
45 Center Drive, Room 2AS.55J
Bethesda, MD 20892-6200
Telephone: (301) 594-5520
FAX: (301) 480-2554
Email: tuanmug@nigms.nih.gov
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic Assistance No.
93.821. 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 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.
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