SUPPLEMENTS FOR THE STUDY OF COMPLEX BIOLOGICAL SYSTEMS

Release Date:  January 16, 1998

PA NUMBER:  PA-98-024

P.T.

National Institute of General Medical Sciences

PURPOSE

The purpose of this initiative is to support new quantitative
approaches to the study of complex, fundamental biological
processes by encouraging non-traditional collaborations across
disciplinary lines.  The National Institute of General Medical
Sciences (NIGMS) will provide supplements to existing NIGMS grants
to support the salary and expenses of collaborating investigators
such as physicists, engineers, mathematicians, and other experts
with quantitative skills relevant to the analysis of complex
systems.  It is expected that the collaboration will result in new
directions for the parent project, or new research projects that
will compete for independent funding.

ELIGIBILITY REQUIREMENTS

The principal investigator must have an active investigator-
initiated research grant funded by NIGMS (R01, R37, or P01).  In
all cases, the parent grant must have at least one year of support
remaining at the time of the supplemental award.  An investigator
will be allowed one supplemental award at a time under this
program.  Because the supplements are intended to develop cross-
disciplinary research collaborations, the prospective collaboration
must propose new approaches to the subject area of the parent
grant.  Therefore, the expertise of the prospective collaborator
should not substantively overlap that of the principal
investigator.  The collaborator need not have prior experience with
biological problems, but must have established credentials in the
area of his/her expertise.  The proposed research project also must
be distinct from the collaboratorþs ongoing research.  Prospective
collaborators with NIH support are not eligible for this program
unless a compelling case is made that the existing NIH grant
neither overlaps, nor is an alternative source of funds for, the
proposed collaboration.  Investigators are encouraged to contact
the program director of the parent grant or NIGMS staff listed
under INQUIRIES, to discuss eligibility requirements.

Applications may be submitted by foreign, domestic, for-profit and
non-profit organizations, both public and private, such as
universities, colleges, hospitals, laboratories, units of state and
local governments, and eligible agencies of the Federal government. 
Principal Investigators are encouraged to consider collaborators
who are in the racial/ethnic minority, women, and persons with
disabilities.

MECHANISM OF SUPPORT

The intent of this initiative is to provide for an expansion of the
scope of the parent grant.  Therefore, awards will be made through
the peer-reviewed competitive supplement mechanism.  Salary, fringe
benefits and travel expenses (if needed to establish the
collaboration) will be provided for the collaborating investigator. 
Additional funds may be requested for supplies and well-justified
items of equipment.  The term of award can extend to the end of the
funded period.

RESEARCH OBJECTIVES

Research in the basic biomedical sciences has provided dramatic
advances in our knowledge of the fundamental mechanisms underlying
life processes.  These advances owe their success in large part to
a paradigm that focuses attention on a limited number of model
systems and develops and uses analytic methods of exquisite
sensitivity and specificity, such as genetics and the tools of
molecular biology.  The strategy has been to identify individual
cellular components, elucidate their structure, function and
regulation, and confirm their role at the cellular, subcellular and
molecular levels of organization.  Recent technological advances in
the genomic sciences, moreover, promise to extend our information
base to all the gene products of the cell, with an ever-increasing
rate of data accumulation and need for analysis.

NIGMS anticipates that biomedical research will become increasingly
focused on the understanding of biological functions at a higher
order of complexity.  If the goal is to predict the behavior of the
cell, tissue or organism, especially when perturbed by disease
states, it will be necessary to discover and represent the
contributing factors and the dynamics and system rules that govern
the collective behavior of these factors.  Mathematical models and
simulations, with reliance on computers to handle large quantities
of data, are among the tools that are being developed to analyze
and represent complex processes.  Promising research areas include,
but are not limited to: 1) the analyses of patterns of gene
expression and signal transduction in embryogenesis; 2) the
description of forces modulating the interaction of molecules in
dynamic, complex assemblies such as the mitotic apparatus; 3) the
analysis of the control circuitry regulating the flow of
metabolites at both gene and enzymatic levels; 4) the analysis of
tissue and organ-level homeostatic mechanisms; and 5) the
development of methods to identify genes and environmental
influences that contribute to complex traits.  Different levels of
organization most likely will require different treatments;
understanding the dynamics of cell motility may require entirely
different approaches from analyzing complex gene-environment
interactions that underlie drug action, or understanding systemic
host responses to trauma, burn, or other injury. Generically, these
types of problems reflect the traditional interests of the
quantitative disciplines such as mathematics, chemistry, physics,
engineering, and computer science. Although individuals with skills
in these disciplines have a history of contributing to the
understanding of biological phenomena, such as the solution of
macromolecular structure, there are relatively few who have applied
this expertise to the study of biological problems at more complex
levels of organization.  NIGMS recognizes that biomedical
scientists have begun to express interest in understanding
experimental systems at a higher level of complexity.  Because
often there are formidable obstacles to the development of cross-
disciplinary collaborations, NIGMS offers this initiative to
encourage and facilitate the process.

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 is 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 have been
published in the Federal Register of March 28, 1994 (FR 59 14508-
14513) and in the NIH Guide for Grants and Contracts, Volume 23,
Number 11,
March 18, 1994.

APPLICATION PROCEDURES

Applications are to be submitted on the grant application form PHS
398 (rev. 5/95) and will be accepted at the standard application
deadlines as indicated in the application kit.  Applications kits
are available at most institutional offices of sponsored research
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: ASKNIH@od.nih.gov.

The title and number of this program announcement must be typed in
Section 2 on the face page of the application.

Information regarding active or pending sources of project-specific
support available to the principal investigator and collaborator is
an important part of the review and award process and must be
included in the Other Support section page of the PHS 398.

The application must provide the curriculum vitae of the proposed
collaborating investigator, including a detailed list of
publications.

The application must include a specific research project based on
the aims of the parent grant, but which expands the scope to
incorporate new conceptual and/or technical quantitative approaches
that are the basis for the collaboration.  The research project may
become the basis for the collaborator to seek independent funding
or to cooperate in a continuing effort with the sponsoring NIGMS
grantee.  The research proposal must make clear the unique
opportunity afforded by the collaborating investigatorþs expertise
to the quantitative analysis of complex biological problems. A
letter of commitment from the collaborator must be submitted as a
supporting document with the application. The letter should be
countersigned by an institutional official if the collaborator is
at a different institution than the one submitting the parent grant
application.

The completed original application and five legible copies must be
sent or delivered 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)

REVIEW CONSIDERATIONS

Applications will be reviewed for scientific and technical merit by
an appropriate initial review group of the Center for Scientific
Review. Following the initial scientific-technical review, the
applications will 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 review, comments on
the following aspects of the application will be made 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 the assignment of the
overall score.

1.  Significance.  Does the proposed collaboration add substantial
value to the problem under study in the parent grant? 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?

2.  Approach.  Are the conceptual framework, design, methods, and
analyses adequately developed, well integrated, and appropriate to
the aims of the parent project?  Does the applicant acknowledge
potential problem areas and consider alternative tactics?

3.  Innovation.  Does the collaborative project employ novel
concepts, approaches or method?  Are the aims original and
innovative? Does the project challenge existing paradigms or
develop new methodologies or technologies?

4.  Investigator and Collaborator.  Are the investigator and
collaborator appropriately trained and well suited for the
collaborative project?  Is the work proposed appropriate to the
experience level of the principal investigator, the collaborator,
and other researchers on the project (if any)?

5.  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 in order to establish a useful
collaboration?
Is there evidence of institutional support?

AWARD CRITERIA

Applications will compete for available funds with all other
approved applications assigned to NIGMS.  The following will be
considered in making funding decisions:

The quality of the proposed collaborative project as determined by
peer review; the availability of funds; the extent to which the
proposed collaborative project will recruit investigators of
appropriate expertise, who might otherwise not have the
opportunity, to contribute to the quantitative study of complex
biomedical problems.

INQUIRIES

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

Direct inquiries regarding programmatic issues to either the
program director listed on your award statement, or:

Dr. James C. Cassatt
Division of Cell Biology and Biophysics
National Institute of General Medical Sciences
45 Center Drive, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-0828
FAX:  (301) 480-2004
Email:  czj@cu.nih.gov

Dr. Judith H. Greenberg
Division of Genetics and Developmental Biology
National Institute of General Medical Sciences
45 Center Drive, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-0943
FAX:  (301) 480-2228
Email:  greenbej@nigms.nih.gov

Dr. Michael E. Rogers
Division of Pharmacology, Physiology and Biological Chemistry
National Institute of General Medical Sciences
45 Center Drive, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-3827
FAX:  (301) 480-2802
Email:  rogersm@nigms.nih.gov

Direct inquiries regarding fiscal matters to either the grants
management specialist listed on your award statement, or:

Ms. Carol Tippery
Grants Management Office
National Institute of General Medical Sciences
45 Center Drive, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-5135
FAX:  (301) 480-1969
Email:  tipperyc@nigms.nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance Numbers 93.821, 93.859, and 93.862.  Awards are made
under authorization of the Public Health Service Act, as amended
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, and portion of a facility) in which regular or
routine education, library, day care, health care or early
childhood development services are provided to children.  This is
consistent with the PHS mission to protect and advance the physical
and mental health of the American people.

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