BAC LIBRARY PRODUCTION

Release Date:  April 18, 2001

RFA:  RFA-HG-01-002 (Request for competing renewal applications, see NOT-HG-05-003)

National Human Genome Research Institute
 (http://www.nhgri.nih.gov)
National Center for Research Resources
 (http://www.ncrr.nih.gov)

Letter of Intent Receipt Date:  June 1, 2001
Application Receipt Date:       June 27, 2001

PURPOSE

The National Human Genome Research Institute (NHGRI) and the National Center 
for Research Resources (NCRR) invite applications for support of efforts to 
produce BAC libraries from the DNA of a number of different eukaryotic 
organisms that are important in biomedical and biological research.  Under 
this initiative, NHGRI and NCRR expect to support the production of 10 new 
libraries in the first 12-18 months of funding, and to develop the capacity to 
double this rate subsequently if there is a continuing demand for new BAC 
libraries, with the possibility of constructing as many as 50 BAC libraries in 
three years.

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), 
Title of RFA, is related to several priority areas including cancer, heart 
disease and stroke, diabetes and chronic disability conditions, and maternal 
and infant health. Potential applicants may obtain a copy of "Healthy People 
2010" at http://www.health.gov/healthypeople/.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign, for-profit and non-
profit organizations, public and private, such as universities, colleges, 
private companies, hospitals, laboratories, units of State and local 
governments, and eligible agencies of the Federal government.  Applications 
from foreign institutions will be accepted.  Racial/ethnic minority 
individuals, women, and persons with disabilities are encouraged to apply as 
Principal Investigators.

MECHANISM OF SUPPORT

The administrative and funding mechanism to be used to support this program 
will be the Cooperative Agreement (U01), an "assistance" mechanism, which is 
distinguished from a regular research grant in that substantial scientific 
and/or programmatic involvement by NHGRI and NCRR staff with the awardee is 
anticipated. The cooperative agreement is used when participation by NIH staff 
is warranted to support and/or stimulate the recipient"s activity by 
involvement in and otherwise working jointly with the award recipient in a 
partner role, NIH staff will not assume direction, prime responsibility, or a 
dominant role in the activity.  Details of the responsibilities, 
relationships, and governance of the studies funded under cooperative 
agreement(s) are discussed later in this document under the section "Terms and 
Conditions of Award".  

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 December 1, 2001.

FUNDS AVAILABLE

The NHGRI and NCRR together intend to commit a total of approximately $2.5 
million in FY 2002 to fund two to four new and/or competitive continuation 
grants in response to this RFA.  Applicants may request a project period of up 
to three years. Because the nature and scope of the research proposed by 
different investigators may vary, it is anticipated that the size of each 
award would also vary. Although the financial plans of the NHGRI and NCRR 
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. 

RESEARCH OBJECTIVES

Background

Over the past several years, the bacterial artificial chromosome (BAC) has 
emerged as the vector system of choice for the construction of the large-
insert chromosomal DNA libraries that are needed in genomic studies.  The BAC 
cloning system allows the isolation of genomic DNA fragments that are large 
enough (80 to >200 kilobases [kb]) to be useful for both genomic sequence 
determination and for a variety of functional studies.  BAC clones are less 
prone to artifacts than either of the other available vector systems for 
large-fragment cloning, cosmids (cosmid libraries generally contain 
considerably more unstable clones than BAC libraries) and yeast artificial 
chromosomes (YACs, BAC libraries contain significantly fewer chimeric clones).  

To date, the complete sequencing of all large eukaryotic genomes (including C. 
elegans, D. melanogaster, A. thaliana and H. sapiens) has involved BAC clones.  
Recent experience in sequencing the human genome shows that determination of 
the sequence of a large, repeat-rich genome requires the availability of a 
clone map for localizing sequence contigs and for assembling regions 
containing repeated sequences.  While whole genome shotgun sequence data will 
likely be part of any strategy adopted to sequence such genomes, it does not 
obviate the need for well-mapped BAC clones and therefore for BAC libraries.  

Because BAC clones are relatively large and appear to represent an organism"s 
genome well, the BAC system will also be the vehicle of choice for the 
isolation of targeted regions of genomic DNA from additional human 
individuals, other mouse strains, or other organisms for specific biological 
studies.  

BAC libraries representing the genomes of a small number of organisms have 
been constructed and are publicly available 
http://www.chori.org/bacpac/home.htm.  It is of concern to the NHGRI and NCRR 
that the current national capacity for making BAC libraries may be too low to 
meet future demand, and that BAC library construction could become a 
bottleneck in the advancement of the application of genomic approaches to 
biomedical and biological research.  

Research Objectives

NHGRI currently funds only a limited amount of BAC library construction, 
sufficient to produce about two 10-fold deep mammalian libraries per year.  
With the increasing interest in genomic approaches to biological research, 
there is concern that this level will not be sufficient to produce the number 
of libraries that will be needed and that the consequent lack of availability 
of more libraries could become a bottleneck to research.  To increase the 
number of available BAC libraries, NHGRI and NCRR wish to encourage the 
establishment of additional BAC library-making capacity.  

The primary purpose of this solicitation is to ensure an adequate capacity for 
BAC library making and to generate a large number of BAC libraries that will 
be generally useful to the biological and biomedical research communities.  
There are several factors that affect the difficulty of and time required to 
make a BAC library, and therefore that affect the cost of a library.  
Prominent among these are the size of the genome being cloned, the method used 
to generate the sub-genomic fragments being cloned, the number of clones in 
the library, and the average size of the cloned genomic DNA fragments 
(inserts).

Typically, the most useful BAC libraries contain at least a 10-fold (10X) 
representation of the organism"s genome (an average region of the genome is 
present ten times in the library, the product of the number of clones and the 
average insert size divided by the size of the genome determines the "depth," 
or "fold coverage" of the library). However, the cloning efficiency is not 
usually uniform for all of the fragments.  Therefore, to ensure that a library 
contains as much of the genome as possible, libraries with as much as 20X 
representation have been produced.

Similarly, typical BAC libraries contain inserts that average about 150 kb in 
size.  However, for some purposes, such as generating a fingerprint map of the 
genome, larger inserts are preferable.  Libraries containing fragments of 200 
kb average size have been made, but are usually considerably more difficult 
and more expensive to construct than those containing smaller inserts.

There are basically two methods used to generate DNA fragments for library 
construction.  The most commonly used method is partial digestion of genomic 
DNA with a restriction enzyme.  This is a proven technique that is relatively 
easy to control.  However, the sites at which the DNA is cut are fixed by the 
location of the restriction enzyme recognition sites, so the inserts in these 
libraries are not random. Furthermore, if the restriction sites are located in 
repeated DNA sequences, there will be problems in making use of the end 
sequence data.  Random DNA fragments can be generated by shearing the DNA.  
However, the techniques for producing and cloning sheared DNA fragments in the 
100 to 200 kb range are not routine, and the methods for construction of 
randomly-sheared BAC libraries are still under development.  Applicants should 
take into account the need to improve the process of library production, as 
well as the need for a reliable level of BAC library construction capacity.

As a guideline, the NHGRI and NCRR are planning to support a national capacity 
to make at least ten 10X libraries of human-sized genomes (three gigabases) 
per year.  Applicants may propose any level of capacity that they feel is 
appropriate to their capabilities, NHGRI and NCRR are willing to fund as many 
as four different laboratories under this RFA.  Applicants should also address 
the issues of library quality and cost of library production.

The quality of a BAC library is extremely important in determining the actual 
utility of the library.  Applicants must propose a plan for assessing the 
quality of the libraries produced including, but not limited to, parameters 
such as the fraction of clones containing inserts, the distribution of insert 
sizes, the fraction of chimeric clones, and the fraction of unstable clones.

At present, the relatively high cost of making a BAC library limits the number 
of libraries that can be constructed each year with NHGRI and NCRR support.  
To the degree that library production costs can be reduced, the number of 
libraries produced each year could be increased without an increase in overall 
spending on this component of the NHGRI and NCRR research programs.  
Applicants should, therefore, discuss plans for improving methods for BAC 
library construction, particularly those that would lead to a reduction in the 
cost of library production over the term of the award (three years).   In 
addition to approaches based on increasing the efficiency of current library 
production methods, applicants may include a technology development component 
in their proposals.  

Applicants need not attempt to enumerate all of the organisms for which they 
plan to prepare BAC libraries.  At present, neither the NIH nor the applicants 
can predict the actual needs that the research enterprise will have for 
particular BAC libraries over the next few years.  The NHGRI is currently 
developing a process that will allow the establishment and dissemination, on 
an on-going basis, of a set of priorities for NHGRI-supported genomic 
research, including the on-going need for new BAC libraries.   By the time 
applications submitted in response to this RFA are funded, the NHGRI will have 
implemented that process and, through the cooperative agreement mechanism, 
NHGRI staff and awardees will be able to decide which BAC libraries to produce 
and on what schedule to produce them.

Other institutes and centers at the NIH may also identify, or may have already 
identified, specific organisms for which they will want BAC libraries 
constructed.  For example, the NCRR has a particular interest in BAC libraries 
from non-human primate species. These priorities will be integrated into those 
identified by the NHGRI for BAC library making at the time of award.

Applicants should describe their plans for the release and dissemination of 
data about the libraries they produce.  While funds for distribution of the 
libraries should not be requested in applications responding to this RFA, 
applicants should discuss any plans they have ,for library distribution (for 
example, distribution by a company to which the library is given or through a 
distribution service set up by the awardee which recovers its cost through 
charges to the requestors).  The adequacy of the plans for dissemination of 
the libraries and data about the libraries is included as a review criterion 
for this RFA.  Once a dissemination plan is worked out that is satisfactory to 
the grantee, NHGRI and NCRR it will be made a condition of the award.  
Applicants should also be familiar with the NIH statements regarding 
intellectual property of resources developed with Federal funds 
(http://www.ott.nih.gov/policy/rt_guide_final.html)

In summary, applicants for awards under this RFA:

o  should provide information about their prior experience in making BAC 
libraries, 

o  should discuss all issues currently associated with the construction, 
evaluation and distribution of BAC libraries, 

o  should address the approaches they propose to take toward library 
construction,

o  should address the issue of library production costs and ways to reduce 
costs,

o  should discuss approaches to disseminating of the libraries and information 
about the libraries,

o  may include proposals to improve library-making technology, and

o  do not have to propose a set of specific organisms for which libraries will 
be made.

SPECIAL REQUIREMENTS FOR COOPERATIVE AGREEMENTS

Definitions 

ARBITRATION PANEL: A panel that is formed to review scientific or programmatic 
disagreement (within the scope of the award) that may arise between an award 
recipient and NHGRI.  It will be composed of three members: (1) a designee of 
the awardee, (2) an NHGRI designee, and (3) a third designee with relevant 
expertise who is chosen by the other two. The Arbitration Panel will help 
resolve both scientific and programmatic issues that develop during the course 
of work and that restrict progress. 

AWARDEE: The institution to which the cooperative agreement is awarded. 

COOPERATIVE AGREEMENT: An assistance mechanism in which there is anticipated 
to be substantial involvement by NHGRI program staff with the recipient 
organization during the performance of the planned activity. 

NHGRI PROGRAM DIRECTOR: A scientist of the NHGRI extramural staff who provide 
normal stewardship for the awards and who, in addition, has substantial 
scientific/programming involvement during conduct of this activity, as defined 
in the terms and conditions of award. The nature of this involvement is 
described below.

PRINCIPAL INVESTIGATOR (P.I.): The person who assembles the project, is 
responsible for submitting the application in response to this RFA, and is 
responsible for the performance of the project. The Principal Investigator 
will coordinate project activities scientifically and administratively. 

SCIENTIFIC ADVISORY PANEL (SAP): A panel that evaluates the progress of the 
NHGRI large-scale sequencing program and provides recommendations to the 
Director, NHGRI, about continued support of all components of the program. The 
Advisory Panel is composed of four to six senior scientists with relevant 
expertise who are not P.I.s of a cooperative agreement involved in large-scale 
genomic sequencing or BAC library production. 

Terms and Conditions of Award 

The following terms and conditions will be incorporated into the award 
statement of each cooperative agreement awarded under RFA HG-01-002 and will 
be provided to the Principal Investigator, as well as the appropriate 
institutional official, at the time of award.  The following special terms of 
award are in addition to, and not in lieu of, otherwise applicable OMB 
administrative guidelines, DHHS grant administration regulations at 45 CFR 
Parts 74 and 92 [Part 92 are applicable when State and local Governments are 
eligible to apply], as are other DHHS, NIH, and NIH grant administration 
policies: 

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

(2) P.I. Rights and Responsibilities: 

The P.I. will have the primary responsibility for defining the details for the 
BAC library production project within the guidelines of RFA HG-01-002 and for 
performing the scientific activities. The P.I. will agree to accept close 
coordination, cooperation, and participation of NHGRI staff in those aspects 
of scientific and technical management of the project as described under 
"NHGRI Program Staff Responsibilities." 

The P.I. of a BAC library production center will: 

o  Determine experimental approaches, design protocols, set project milestones 
and conduct experiments,

o  Ensure that the BAC libraries produced meet the quality standards and cost 
agreed upon at the time of award, 

o  Ensure that the BAC clone resources developed as part of this project are 
made publicly available and that results are published, 

o  Ensure that the decisions about the BAC libraries produced under NHGRI and 
NCRR funding meet the needs of the Institute/Center"s programs, as determined 
at the time of initiation of each library-making effort,

o  Coordinate and collaborate with other U.S. and international groups 
producing BAC libraries,

o  Be required to accept and implement any common guidelines and procedures 
developed for the BAC library production program. 

(3) NHGRI Program Staff Responsibilities: 

The NHGRI Program Director will have substantial scientific/programmatic 
involvement during the conduct of this activity through technical assistance, 
advice and coordination.  However, the role of NHGRI staff will be to 
facilitate and not to direct the activities. It is anticipated that decisions 
in all activities will be reached by consensus between the Principal 
Investigator(s) and NHGRI staff.  The Program Director will: 

o  Participate in discussing research priorities, including choice of 
organisms from which to make BAC libraries, deciding optimal research 
approaches and protocol designs (including quality assessment), and 
contributing to any necessary adjustment of research protocols or approaches.  

o  Serve as liaison, helping to coordinate activities among and for the 
awardees, including acting as a liaison to the NHGRI and the other Institutes 
and Centers of the NIH, and as an information resource about extramural genome 
research activities.

o  Coordinate the efforts of the BAC library makers with the NHGRI sequence 
production program, with other U.S. large-scale sequencing efforts and with 
the international sequencing community.

o  Assist awardees in the development, if needed, of policies for dealing with 
situations that require coordinated action. 

o  Periodically report on the progress of the BAC library construction program 
to the NHGRI Director, the Sequencing Advisory Panel and other interested NIH 
Institutes and Centers. 

o  Assist in promoting the availability of the BAC libraries and related 
resources developed in the course of this project to the scientific community 
at large. 

o  Retain the option to recommend, with the advice of the Scientific Advisory 
Panel, the withholding or reduction of support from any cooperative agreement 
that substantially fails to achieve its goals at the quality and cost agreed 
to at the time of award, fails to remain state of the art in its library-
making capabilities, or fails to comply with the Terms and Conditions of the 
award. 

(4) Collaborative Responsibilities
 
The awardees and Program Director will be responsible for:

o  Discussing progress in meeting the research community’s need for BAC 
libraries.

o  Advising NHGRI as to how the requisite number of BAC libraries can be met 
within the stated goals of time and accuracy, and within budget. 

o  Helping to develop uniform procedures for library quality assessment.  

o  Awardees and Program Directors will be required to accept and implement the 
common guidelines and procedures mutually agreed upon. 

(5) Scientific Advisory Panel (SAP)

The Scientific Advisory Panel will be responsible for reviewing and evaluating 
the progress of the BAC library-making activity, and its coordination with 
large-scale genomic sequencing and other uses of BAC clones in genomic 
research. The membership of the SAP is described in the Definitions section, 
above. The membership of the SAP may be enlarged permanently, or on an ad hoc 
basis, as needed.  

At least once a year, there will be an opportunity, either in a meeting or by 
conference call, for the SAP members to interact directly with the P.I.s of 
the BAC library-making awards.  Annually, the SAP will make recommendations 
regarding progress of the BAC library-making effort and present advice about 
changes, if any, which may be necessary in the BAC library program to the 
Director, NHGRI. 

(6) Arbitration Process 

Any disagreement that may arise on scientific/programmatic matters (within the 
scope of the award), between award recipients and the NHGRI may be brought to 
arbitration.  An Arbitration Panel, whose composition is described in the 
Definitions (above) will be convened.  This special arbitration procedure in 
no way affects the awardee"s right to appeal an adverse action that is 
otherwise appealable in accordance with NIH regulations 42 CFR Part 50, 
Subpart D and HHS regulation at 45 CFR Part 16. 
 
(7) Yearly Milestones 

All awardees participating in the BAC library-making program will be asked to 
define yearly milestones at the time of the award and to update these 
milestones annually at the anniversary date. These will be made a condition of 
the award.  In accord with the procedures described above, NHGRI may withhold 
or reduce funds for any project that substantially fails to meet its 
milestones or to maintain the state of the art. 

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

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

All investigators proposing research involving human subjects should read the 
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research," published in the NIH Guide for Grants and Contracts on 
August 2, 2000 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html), 
a complete copy of the updated Guidelines is available at  
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm.  The 
revisions relate to NIH defined Phase III clinical trials and require: 

o  all applications or proposals and/or protocols to provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable, and

o  all investigators to report accrual, and to conduct and report analyses, as 
appropriate, by sex/gender and/or racial/ethnic group differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age of 21) 
must be included in all human subjects research, conducted or supported by the 
NIH, unless there are scientific and ethical reasons not to include them.  
This policy applies to all initial (Type 1) applications submitted for receipt 
dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the Inclusion of Children as Participants in 
Research Involving Human Subjects that was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and is available at the following URL 
address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html.

Investigators also may obtain copies of these policies from the program staff 
listed under INQUIRIES.  Program staff may also provide additional relevant 
information concerning the policy.

URLS IN NIH GRANT APPLICATIONS OR APPENDICES

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

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, and telephone 
number of the Principal Investigator, the identities of other key personnel 
and participating institutions, and the number and title of the RFA in 
response to which the application may be submitted.  Although a letter of 
intent is not required, is not binding, and does not enter into the review of 
a subsequent application, the information that it contains allows IC staff to 
estimate the potential review workload and plan the review.

The letter of intent should be sent by June 1, 2001 to:

Dr. Jane L. Peterson
Program Director, Large Scale Sequencing
National Human Genome Research Institute 
National Institutes of Health 
Building 31, Room B2B07, MSC2033
Bethesda, MD 20892-2033

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be used in 
applying for these grants.  These forms are available at most institutional 
offices of sponsored research and 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.  Type the RFA 
number on the label.  Failure to use this label could result in delayed 
processing of the application such that it may not reach the review committee 
in time for review.  In addition, the RFA title and number must be typed on 
line 2 of the face page of the application form and the YES box must be 
marked.

The 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.

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 must be 
sent to:

Dr. Rudy Pozzatti
Scientific Review Administrator 
Office of Scientific Review 
Building 31, Room B2B37, MSC 2032
National Human Genome Research Institute 
National Institutes of Health 
Bethesda, MD 20982-2032
Telephone: (301) 402-0838 

Applications must be received by June 27, 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 the CSR and 
responsiveness by the NHGRI.  Incomplete and/or non-responsive applications 
will be returned to the applicant without further consideration.  Applications 
that are complete and responsive to RFA HG-01-002 will be evaluated for 
scientific and technical merit by an appropriate peer review group convened by 
the NHGRI in accordance with the review criteria stated below.  As part of the 
initial merit review, all applications will receive a written critique and 
undergo a process in which only those applications deemed to have the highest 
scientific merit, generally the top half of the applications under review, 
will be discussed, assigned a priority score, and receive a second level 
review by the National Advisory Council for Human Genome Research and the 
National Advisory Research Resources Council.

Review Criteria

The application must be directed toward attaining the programmatic goals as 
stated under RESEARCH OBJECTIVES AND SCOPE. The following criteria will be 
used by peer review groups to evaluate these applications: 

o  Significance:  Does the proposal address the problem outlined in this RFA? 

o  Approach:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well integrated, and appropriate to the aims of the 
project and as outlined in this RFA?  Does the applicant identify potential 
problem areas and consider reasonable solutions? Is the proposed effort likely 
to produce an adequate number of high quality, quality controlled BAC 
libraries during the term of an award?  Are the plans for data and library 
dissemination appropriate?

o  Innovation:  Does the project employ novel concepts, approaches or method 
to improve the scientific utility of BAC libraries?  to reduce the costs, or 
increase the efficiency of constructing BAC libraries? 

o  Data release and library dissemination:  Are the plans for data release and 
library dissemination appropriate?  

o  Investigator:  Is the investigator appropriately trained and well suited to 
carry out this work?  Is the work proposed appropriate to the experience level 
of the principal investigator and other researchers (if any)?

o  Environment:  Does the scientific environment in which the work will be 
done contribute to the probability of success?  Do the proposed experiments 
take advantage of unique features of the scientific environment or employ 
useful collaborative arrangements?  Is there evidence of institutional 
support?

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

o  The adequacy of plans to include both genders, minorities and their 
subgroups, and children as appropriate for the scientific goals of the 
research.  Plans for the recruitment and retention of subjects will also be 
evaluated.

o  The reasonableness of the proposed budget and duration in relation to the 
proposed research.

o  The adequacy of the proposed protection for humans, animals or the 
environment, to the extent they may be adversely affected by the project  
proposed in the application.

Schedule

Letter of Intent Receipt Date:    June 1, 2001
Application Receipt Date:         June 27, 2001
Peer Review Date:                 early August, 2001
Council Review:                   September 10-11 , 2001
Earliest Anticipated Start Date:  December 1, 2001

AWARD CRITERIA

Awards will be made on the basis of scientific and technical merit as 
determined by peer review, programmatic needs and balance, availability of 
funds and:

o  Likelihood that the proposed program will make a significant contribution 
toward meeting the research community"s need for BAC libraries.

o  Cost effectiveness of the proposed BAC library production effort.

o  Likelihood that any proposed technology development effort will lead to 
significant improvement in the scientific quality of BAC libraries and/or to a 
reduction in the cost of generating BAC libraries.

INQUIRIES

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

Direct inquiries regarding programmatic issues to:

Dr. Jane L. Peterson 
Division of Extramural Research 
National Human Genome Research Institute 
National Institutes of Health 
Building 31, Room B2B07 MSC 2033
Bethesda, MD 20892-2033
Telephone: (301) 496-7531 
FAX: (301) 480-2770 
E-mail:  Jane_Peterson@nih.gov

John D. Harding, Ph.D.
Division of Comparative Medicine
National Center for Research Resources
6705 Rockledge Drive, Suite 6050, MSC 7965
Bethesda, MD 20892-7965
Telephone:  (301) 435-0776
FAX:  (301) 480-3819
E-mail:  hardingj@ncrr.nih.gov

Direct inquiries regarding review issues to:

Dr. Rudy Pozzatti
Scientific Review Administrator 
Office of Scientific Review 
National Human Genome Research Institute 
National Institutes of Health 
Building 31, Room B2B37, MSC 2032
Bethesda, MD 20982-2032
Telephone: (301) 402-0838
FAX:  (301) 435-1580  
E-mail:  Rudy_Pozzatti@nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Jean Cahill 
Grants Administration Branch 
National Human Genome Research Institute 
Building 31, Room B2B34, MSC 2031
Bethesda, MD 20892-2031
Telephone: (301) 402-0733 
FAX: (301) 402-1951 
E-mail:  Jean_Cahill@nih.gov
 
AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.172, (use appropriate program number).  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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

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