Full Text HG-95-003

SEQUENCE OF THE E. COLI GENOME

NIH GUIDE, Volume 24, Number 7, February 24, 1995

RFA:  HG-95-003

P.T. 34

Keywords: 
  Human Genome 
  Nucleic Acid Sequencing 


National Center for Human Genome Research

Letter of Intent Receipt Date:  March 24, 1995
Application Receipt Date:  April 28, 1995

PURPOSE

The National Center for Human Genome Research (NCHGR) invites
applications for research projects to complete the genomic DNA
sequence of the bacterium Escherichia coli (E. coli).

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This Request
for Applications (RFA), Sequence of the E. coli Genome, is related to
several priority areas, including immunization and infectious
diseases, molecular medicine, and others.  Potential applicants may
obtain a copy of "Healthy People 2000" (Full Report:  Stock No.
017-001-00474-0 or Summary Report:  Stock No. 017-001-00473-1)
through the Superintendent of Documents, Government Printing Office,
Washington, DC 20402-9325 (telephone 202-783-3238).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign, for-profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal Government.
Collaborations between scientists in academia and industry are
encouraged, as are applications from minority individuals, persons
with disabilities, and women.

MECHANISM OF SUPPORT

Support for this program will be through the National Institutes of
Health (NIH) individual research project grant (R01).  Responsibility
for the planning, direction, and execution of the proposed project
will be solely that of the applicant.  Awards will be administered
under PHS grants policy as stated in the Public Health Service Grants
Policy Statement.

This RFA is a one-time solicitation.  The total project period for
each application submitted in response to the present RFA may not
exceed two years.  The anticipated award date is September 30, 1995.

FUNDS AVAILABLE

It is anticipated that a total of $2,000,000 (direct and indirect
costs) for the entire project period (not more than two years) will
be available beginning in fiscal year 1995.  It is anticipated that
one or more awards will be made.  The number of awards made will be
contingent upon the quality of applications received and the
availability of funds.  No funds will be available for alteration or
renovation of facilities.

RESEARCH OBJECTIVES

Background

The NCHGR sponsors basic and applied research concerned with the
development and application of new technologies for the
characterization and analysis of the human genome and the genomes of
selected model organisms.  The activities encompassed by the NCHGR
program include genetic and physical mapping, DNA sequencing,
informatics related to mapping and sequencing, gene identification,
technology development that will facilitate all of these efforts, and
studies of the ethical, legal and social implications of genetics
research.

The NCHGR, in conjunction with the Department of Energy, recently
formulated a new five-year plan (Science Vol. 262, pp. 43-46, 1993)
that states one goal to be determining the complete DNA sequence of
the E. coli genome by 1998.  Based on the contributions of a large
community of researchers, approximately 60 percent of the 4.7
megabase E. coli genomic DNA sequence is now available in public
databases, and the largest contiguous E. coli genomic DNA sequence is
approximately 1.6 megabases.  Therefore, determination of
approximately two megabases of new genomic sequence, and linkage of
that sequence with previously determined sequence, is required for
completion of the E. coli sequence.

Objectives and Scope

The purpose of this RFA is to encourage applications from individuals
and groups interested in completing the genomic DNA sequence of the
bacterium E. coli and making it available to the community through
public databases as rapidly as possible.  Given the state-of-the-art
for genomic sequencing, it is reasonable to expect that, with
sufficient resources, a skilled research team would be able to
complete the remainder of the sequence of this 4.7 megabase genome
within two years.  Applicants are expected to apply highly
cost-effective strategies and technologies to sequencing the
remainder of the genome.  It can be anticipated that different
strategies, such as those based mainly on shotgun or directed
approaches could be employed toward this end, but the overall plan
must assure completion of the entire genomic sequence.  If the chosen
strategy were to include the resequencing of some genomic regions
that are already in databases, the applicant must convincingly
demonstrate the cost-effectiveness of such an approach.  Applicants
should include time-lines for completion of the project and
milestones for components of the research plan.  Plans for data
dissemination and goals for sequence accuracy should also be
discussed, particularly in terms of addressing the needs of the
scientific community.  Applicants should also identify and address
issues with respect to management of the project.  This RFA does not
specifically include funds for annotation of the E. coli sequence.
Applicants may propose to include this element in the research
project, but only in context of facilitating completion of the
genomic sequence rapidly and cost-effectively, and within the scope
of the funds available.

LETTER OF INTENT

Because of the specialized interest of this NCHGR program it is
strongly recommended that potential applicants contact NCHGR staff to
discuss research objectives.  Prospective applicants are asked to
submit, by March 24, 1995, 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 this RFA.

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 will allow NCHGR 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 Dr. Robert L. Strausberg at the
address listed under INQUIRIES.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants.  These forms are available at most
institutional offices of sponsored research; from the Office of
Grants Information, Division of Research Grants, National Institutes
of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892,
telephone 301/710-0267; and from the NIH program administrator listed
under INQUIRIES.

The RFA label available in the PHS 398 (rev. 9/91) 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 must be typed on
line 2a 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:

Division of Research Grants
National Institutes of Health
6701 Rockledge Drive, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express mail)

To expedite the review process, at the time of submission, please
send two additional copies of the application to:

Office of Scientific Review
National Center for Human Genome Research
Building 38A, Room 604
38 Library Drive MSC 6050
Bethesda, MD  20892-6050

Applications must be received by April 28, 1995.  If an application
is received after that date, it will be returned to the applicant
without review.  The Division of Research Grants (DRG) 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 DRG 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 DRG
and for responsiveness to the RFA by NCHGR program staff.  Incomplete
and/or non-responsive 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 NCHGR.
Since there is no plan to include site visits in the review process,
it is essential that all applications provide complete details with
respect to all aspects of the proposed research project.  As part of
the initial merit review, a process (triage) may be used by the
initial review group in which applications will be determined to be
competitive or non-competitive based on their scientific merit
relative to other applications received in response to the RFA.
Applications judged to be competitive will be discussed and be
assigned a priority score.  All applicants will receive a summary
statement consisting of the reviewer's written comments essentially
unedited.  Summary statements for competitive applications will also
contain a summary of the review committee's discussion.  The second
level of review will be provided by the National Advisory Council for
Human Genome Research.

Review Criteria

o  scientific and technical significance and originality of proposed
research;

o  appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;

o  qualifications and research experience of the Principal
Investigator and staff to conduct a large-scale DNA sequencing
project;

o  availability of the resources necessary to perform the research;

o  appropriateness of the proposed budget and duration in relation to
the proposed research;

Additional scientific/technical merit criteria specific to this RFA
are:

o  degree to which the project assures that the sequence of the E.
coli genome  will be completed and deposited in a public database by
the end of the two year period.

o  degree to which the applicant clearly defines sequencing goals
with respect to throughput of finished sequence during the time frame
of the project.

o  degree to which the applicant addresses the issues of sequence
accuracy and  finishing.

o  track record of the applicant in generating and disseminating
large contiguous segments (at least several hundred kilobases) of
genomic DNA sequence.

o  track record of the applicant in successfully managing a
large-scale genomic DNA sequencing project.

AWARD CRITERIA

The anticipated date of award is September 30, 1995.  The following
criteria will be considered in making funding decisions.

o  quality of the proposed project as determined by peer review;

o  responsiveness of the proposed project to the goals of this RFA;

o  availability of funds.

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged.
The opportunity to clarify any issues or questions from potential
applicants is welcome.

Direct inquiries regarding programmatic issues to:

Robert L. Strausberg, Ph.D.
Sequencing Technology Branch
National Center for Human Genome Research
Building 38A, Room 610
38 Library Drive MSC 6050
Bethesda, MD  20892-6050
Telephone:  (301) 496-7531
FAX:  (301) 480-2770
Email:  Robert_Strausberg@nih.gov

Direct inquiries regarding fiscal matters to:

Jean M. Cahill
Grants and Contracts Management Section
National Center for Human Genome Research
Building 38A, Room 613
38 Library Drive MSC 6050
Bethesda, MD  20892-6050
Telephone:  (301) 402-0733
FAX:  (301) 402-1951
Email:  Jean_Cahill@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance No. 93.172.  Awards are made under authorization of the
Public Health Service Act, Title IV, Part A (Public Law 78-410, as
amended by Public Law 99-158, 42 USC 241 and 285) and administered
under PHS grants policies and Federal Regulations 42 CFR 52 and 45
CFR 74.  This program is not subject to the intergovernmental review
requirements of Executive Order 12372 or Health Systems Agency
review.

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