Full Text HG-96-001
 
LARGE SCALE FUNCTIONAL ANALYSIS OF THE YEAST GENOME
 
NIH GUIDE, Volume 25, Number 12, April 19, 1996
 
RFA:  HG-96-001
 
P.T. 34

Keywords: 
  Molecular Genetics 
  Nucleic Acid Sequencing 

 
National Center for Human Genome Research
National Cancer Institute
 
Letter of Intent Receipt Date:  August 9, 1996
Application Receipt Date:  September 6, 1996
 
THIS RFA USES THE "JUST-IN-TIME" CONCEPT.  THE FULL RFA INCLUDES
DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS AND MUST
BE USED WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS RFA.
 
PURPOSE
 
The DNA sequence of the Saccharomyces cerevisiae genome will be
completed in the very near future.  The availability of the entire
yeast DNA sequence will provide experimental and computational
biologists with an incomparable resource for systematic and
comprehensive analyses of the genetic basis of biological function
including, for example, analyses of gene function, the regulation of
gene expression, the interactions between functional and structural
elements, and the biological consequences of genomic organization.
This Request For Applications (RFA) calls for research projects that
will enrich the yeast sequence with biological information in rapid
and comprehensive, and efficient ways and/or take advantage of the
complete DNA sequence of S. cerevisiae in new, global approaches to
the study of biological phenomena important for human health and
disease, including cancer.  These studies should be based on
technologies that are efficient, cost-effective and scalable to the
entire yeast genome, and that use and/or add value to the complete
DNA sequence.  Applications to develop new technologies that could be
applied to the yeast genome in a timely manner will also be
considered. It is anticipated that these studies will provide
functional information, resources and infrastructure that will serve
as a platform for more in- depth, specific studies in the future.
 
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 RFA,
Large-Scale Functional Analysis of the Yeast Genome, is related to
several priority areas, including cancer, heart disease and stroke,
diabetes and chronic disability conditions, maternal and infant
health, 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 202-512-1800).
 
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.  Applications from
social/ethnic minority individuals, women, and persons with
disabilities are encouraged.  Applications from foreign institutions
will not be accepted.  However, subcontracts to foreign institutions
are allowable, with sufficient justification.
 
MECHANISM OF SUPPORT
 
This RFA will use the National Institutes of Health (NIH) individual
research project grant (R01), program project grant (P01) and pilot
project/feasibility study (R21) mechanisms.  The R21 mechanism is
used to support highly creative approaches for which substantial
preliminary data are not yet available. Specific information about
the R21 grant mechanism can be found in the NCHGR Program
Announcement PAR-94-046, "Pilot Projects or Feasibility Studies for
Genomic Analysis."  The total project period for an application
submitted in response to the present RFA may not exceed three years
and the direct cost per year for R01 or P01 grants must not exceed
$500,000.  R21 grants will be limited to $100,000 direct costs per
year for a maximum of two years.  The R21 grants are not renewable,
but future project continuation is possible through other grant
mechanisms such as the R01 or P01.  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.  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 April 1, 1997.
 
FUNDS AVAILABLE
 
It is anticipated that approximately $ 2.5 million (total costs) will
be available for this initiative in fiscal year 1997.  Awards
pursuant to this RFA are contingent upon the availability of funds
for this purpose.  The amount of funding for these projects may be
increased if a large number of highly meritorious applications are
received and if funds are available.  Only applications found to be
of high scientific merit will be considered for funding and all of
the funds will not be spent if there are not enough highly
meritorious applications.  Funding in future years will be subject to
the availability of funds. Because the scope of the research proposed
in response to this RFA encompasses the interest of several NIH
Institutes and Centers, applications might receive dual assignments
based on the established PHS referral guidelines.
 
SPECIAL REQUIREMENTS
 
Streamlining Efforts
 
This RFA will use the "Just-In-Time" streamlined approach recently
introduced at the NIH.  The "Just-In-Time" concept allows applicants
to submit certain information only when there is a possibility for an
award.  It is anticipated that these changes will reduce the
administrative burden for applicants, reviewers, and NIH staff.
Instructions for completing the "Biographical Sketch" have been
modified.  In addition, "Other Support" information and the
application "Checklist" page are not required as part of the initial
application.  If there is a possibility for an award, this
information will be requested by NIH staff following the initial
review.  The APPLICATION PROCEDURES section of this RFA provides
specific details of modifications to standard PHS 398 application kit
instructions.
 
Post-award Management
 
During the course of the grant period, technologies will improve and
the rate of progress and focus of work supported by the grant(s) may
change.  It is expected that the principal investigator(s) will make
any necessary adjustments in scientific direction to accommodate the
changing environment.  During the course of the award period, the
principal investigator(s) may be invited to meet with NIH program
staff in Bethesda, MD to review scientific progress. Other scientists
external to and knowledgeable about these studies may also be invited
to participate.
 
RESEARCH OBJECTIVES
 
Background
 
A major milestone in genomic and genetic analysis is the imminent
completion of the sequence of the yeast Saccharomyces cerevisiae;
this will be the first eukaryotic genome to be sequenced in its
entirety.  This accomplishment will represent the efforts of an
international consortium of laboratories in Europe, Canada, Japan and
the United States.
 
S. cerevisiae is an important model organism for the genetic analysis
of biological processes because the wide variety of genetic
manipulations to which it is amenable readily allow determination of
the function of genes and regulatory elements.  The relevance of
studies in yeast to human biology has been re-emphasized in recent
years.  There is an increasing number of examples in which homology
between yeast and human genes, combined with an understanding of the
function of the yeast genes, has allowed significant insight into the
function of the human genes. For example, the phenotype of yeast
carrying a mutant MSH2 gene was found to be similar to the phenotype
of certain human tumor cells; this led to the cloning of the human
homolog hMSH2, a gene implicated in one form of hereditary
non-polyposis colon cancer (Strand et al., (1993) Nature 365:274-6;
Fishel et al., (1993) Cell 75: 1027-38.)  Similarly, the study of
yeast MEC1 and TEL1 genes has provided insight into the function of
the human ATM gene, mutations in which cause ataxia telangiectasia
(Weinert et al., (1994) Genes Dev 8: 652-65; Morrow et al., (1995)
Cell 82: 831-840).  In addition to information about homology
relationships, a number of human genes have been shown to function in
yeast, allowing new approaches to their study.
 
The availability of the entire yeast DNA sequence will provide
experimental and computational biologists with an incomparable
resource for systematic and comprehensive analyses of the genetic
basis of biological function.  The ability to do these analyses on a
genomic level offers the tremendous advantage of economy of scale and
will significantly increase the rate at which biological information
is acquired.  As the DNA sequence of S. cerevisiae is annotated by
such information, the increasingly comprehensive understanding of the
yeast genome will provide a wealth of information that can be applied
to the study of human biology, including genetic diseases and other
traits.
 
Objectives and Scope
 
To take advantage of the opportunities presented by the new resource
that the complete DNA sequence of S. cerevisiae represents, this RFA
calls for research projects that will enrich the yeast sequence with
biological information in rapid, comprehensive and efficient ways
and/or will use the complete DNA sequence in new, global approaches
to the study of biological phenomena important for human health and
disease, including cancer.  These studies should be based on
technologies that are efficient, cost-effective and scalable to the
entire yeast genome, and that use and/or add value to the complete
DNA sequence.  Applications to develop new technologies that could be
applied to the yeast genome in a timely manner will also be
considered.  Studies to determine the function of the product of a
particular gene or family of genes, or that focus on computational
approaches to the analysis of the yeast genome will not be considered
under this RFA.  Further, this solicitation is limited to studies on
S. cerevisiae.
 
Areas of research encouraged include, but are not limited to:
 
o  Comprehensive studies to determine whether coding sequences
identified computationally are transcribed in vivo;
 
o  Comprehensive studies that will provide insight into the
biological role that gene products play in the cell;
 
o  Comprehensive studies to elucidate the role of non-coding
functional genomic elements;
 
o  Comprehensive studies to elucidate the interactions amongst
functional elements of the genome;
 
o  Comprehensive studies to analyze genome organization and its
effect on cellular functions;
 
o  Development of new technologies, or refinement of existing
technologies that are robust, and provide significant improvements
over current technologies, and that can be applied to genomic
analyses in a timely manner; and
 
o  Development of unique resources to carry out these types of
studies.
 
Applicants should address the following issues:
 
o  How the proposed research approach will use and/or add value to
the complete yeast genomic sequence;
 
o  Advantages of the proposed approach over existing approaches;
 
o  Value of the forthcoming data and technology in furthering the
understanding of eukaryotic biology;
 
o  Value and exportability of the forthcoming resources;
 
o  How this research will complement related studies; and
 
o  Plans for making data and resources broadly accessible.
 
The sharing of materials and data in a timely manner has been an
essential element in the rapid progress made in genome research.
Public Health Service (PHS) policy requires that investigators make
the results and accomplishment of funded activities publicly
available.  The advisors to the NIH and the DOE genome programs have
developed a set of guidelines for making data and material resources
available to the scientific community in a timely manner. The
guidelines call for material and information from genome research to
be made available within six months of the time the data or materials
are generated; more rapid sharing is encouraged and has become the
norm in the genome community.  Applications submitted in response to
this RFA should include detailed plans for sharing data and materials
generated through the grant.  Where appropriate, grantees may work
with the private sector in making unique resources available to the
larger biomedical research community at a reasonable cost.  The plans
proposed for sharing and data release will be reviewed for adequacy
by NIH staff prior to award of the grant and the proposed sharing
plan will be made a condition of the award. Investigators may request
funds to defray the costs of sharing materials or submitting data in
their application. Such requests must be adequately justified.
 
LETTER OF INTENT
 
Because of the specialized interest of this RFA, prospective
applicants are strongly encouraged to discuss their research
objectives and the appropriate grant mechanism with NIH staff.
Prospective applicants are asked to submit, by August 9, 1996, 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 subsequent applications, the information
that it contains allows NIH 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:
 
Elise Feingold, Ph.D.
Mapping Technology Branch
National Center for Human Genome Research
Building 38A, Room 614
38 Library Drive  MSC 6050
Bethesda, MD  20892-6050
Telephone:  (301) 496-7531
FAX:  (301) 480-2770
Email:  elise_feingold@nih.gov
 
APPLICATION PROCEDURES
 
The research grant application form PHS 398 (rev. 5/95) is to be used
in applying for these grants.  Applications kits are available at
most institutional offices of sponsored research and may be obtained
from the Grants Information Office, Office of Extramural Outreach and
Information Resources, National Institutes of Health, 6701 Rockledge
Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714,
email:  ASKNIH@odrockm1.od.nih.gov; and from the program director
listed under INQUIRIES.
 
To implement the "Just-In-Time" concept, the following modifications
are made to the standard PHS 398 application instructions:
 
o  BIOGRAPHICAL SKETCH - In addition to the standard information
requested on Form Page 6, the applicant has the option of providing
the title and source of any sponsored support relevant to the
proposed research.
 
o  OTHER SUPPORT - No other support information is required on "Other
Support" pages (Form Page 7).  Selected other support information
relevant to the proposed research may be included in the Biographical
Sketch as indicated above. Complete "Other Support" information will
be requested by NIH staff at a later date if there is a possibility
of an award.
 
o  CHECKLIST - No "Checklist" page is required as part of the initial
application.  A completed Checklist will be requested by NIH staff if
there is a possibility of an award.
 
o  The applicant should provide the name, phone number and E- mail
address of the individual to contact concerning fiscal and
administrative issues if additional information is necessary
following the initial review.
 
The RFA label available in the PHS 398 (rev. 5/95) 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 and three
signed, photocopies, in one package to:
 
DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040
BETHESDA, MD  20892
BETHESDA, MD  20817 (for express/courier service)
 
At the time of submission, two additional copies of the application
must also be sent to:
 
Ms. Linda Engel
Office of Scientific Review
National Center for Human Genome Research
Building 38A, Room 604, MSC 6050
38 Library Drive
Bethesda, MD  20892-6050
 
Applications must be received by September 6, 1996.  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.  The
applicants should also ensure that their revised applications respond
to the review criteria by which the applications in response to this
RFA will be evaluated.
 
REVIEW CONSIDERATIONS
 
Upon receipt, applications will be reviewed for completeness by DRG
and for responsiveness to the RFA by NIH program staff.  Incomplete
applications will be returned to the applicant without further
consideration.  If the application is not responsive to the RFA, NIH
staff will contact the applicant to determine whether to return the
application to the applicant or submit it for review in competition
with unsolicited applications at the next review cycle.
 
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.  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 and assigned a priority score.  All applications will
receive a second level of review by the National Advisory Council for
Human Genome Research.
 
Review criteria will include:
 
o  scientific and technical merit of the proposed research;
 
o  extent to which the experimental approach makes use of and/or adds
value to the complete yeast genomic sequence;
 
o  feasibility of the experimental approach to carry out the proposed
research;
 
o  value of the forthcoming data and/or technology in furthering the
understanding of eukaryotic biology;
 
o  value and exportability of the forthcoming resources;
 
o  likelihood that the project will be able to scale to a genomic
level efficiently and in a timely manner;
 
o  qualifications and research experience of the principal
investigator and staff in the area of the proposed research;
 
o  availability of the resources necessary to perform the research;
 
o  appropriateness of the proposed budget and duration in relation to
the proposed research.
 
o  complementarity to related studies; and
 
o  adequacy of plans to place data and/or material resources in the
public domain in a timely manner.
 
For R21 applications, preliminary data are not required. However, the
applicant does have the responsibility for developing a sound
research plan and for presenting any other information that can be
considered as evidence of feasibility.
 
AWARD CRITERIA
 
The earliest anticipated date of award is April 1, 1997. Factors that
will be used to make award decisions are:
 
o  Quality of the proposed project as determined by peer review;
 
o  Responsiveness of the proposed project to the goals of this RFA;
 
o  Balance among the projects in addressing different experimental
approaches and their complementarity to other ongoing efforts;
 
o  Adequacy of data/material release plan; and
 
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 the following NIH
staff.
 
For general, genomic research projects:
 
Elise Feingold, Ph.D.
Mapping Technology Branch
National Center for Human Genome Research
Building 38A, Room 614
38 Library Drive  MSC 6050
Bethesda, MD  20892-6050
Telephone:  (301) 496-7531
FAX:  (301) 480-2770
Email:  elise_feingold@nih.gov
 
For cancer-related research projects:
 
Cheryl Marks, Ph.D.
Division of Cancer Biology
National Cancer Institute
Executive Plaza North, Room 505
Bethesda, MD  20892-7385
Telephone:  (301) 496-7028
FAX:  (301) 402-1037
Email:  cheryl_marks@nih.gov
 
Direct inquiries regarding fiscal matters to:
 
Ms. Jean Cahill
Grants Management Office
National Center for Human Genome Research
38 Library Drive
Building 38A, Room 613, 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 Part 74.  This program is not subject to the intergovernmental
review requirements of Executive Order 12372 or Health Systems Agency
review.
 
The PHS strongly encourages all grant and contract recipients to
provide a smoke-free workplace and promote the non-use of all tobacco
products.  In addition, Public Law 103-227, the Pro-Children Act of
1994, prohibits smoking in certain facilities (or in some cases, any
portion of a facility) in which regular or routine education,
library, day care, health care or early childhood development
services are provided to children.  This is consistent with the PHS
mission to protect and advance the physical and mental health of the
American people.
 
.

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