Release Date:  June 22, 1999

PA NUMBER:  PA-99-117

National Institute of General Medical Sciences
National Institute of Diabetes and Digestive and Kidney Diseases
National Heart, Lung, and Blood Institute
National Center for Research Resources
National Library of Medicine

STTR Application Receipt Dates:  August 1, December 1, April 1
SBIR Application Receipt Dates:  August 1, December 1, April 1


The purpose of this SBIR/STTR program announcement (PA) is to encourage
research on the development of methodology and technology underpinning the
emerging field of structural genomics, whose goal is the understanding of
protein structural families, structural folds, and the relation of structure
and function.  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 to this PA.


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 PA, Protein Structure SBIR/STTR
Initiative (Structural Genomics), is related to one or more of the priority
areas.  Potential applicants may obtain a copy of "Healthy People 2000" at


Eligibility requirements are described in the Omnibus Solicitation.  Any small
business concern, independently owned and operated by United States citizens
or lawfully admitted permanent resident aliens, which is located in the United
States and is organized for profit, may apply.


Support for the PA is through the SBIR and STTR mechanisms.  Applications can
be submitted for support as Phase I STTR (R41) or Phase I SBIR (R43) grants;
Phase II STTR (R42) or Phase II SBIR (R44) grants; or under the SBIR/STTR
FAST-TRACK option as described in the Omnibus Solicitations.  Phase II
applications in response to this PA will only be accepted as competing
continuations of previously funded NIH Phase I SBIR/STTR awards.  The Phase II
proposal must be a logical extension of the Phase I research.

Information on the FAST-TRACK process and the Omnibus Solicitations is
available at


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

Three recent 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 and isotopic labeling for NMR).  All of these can
likely 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  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 basis 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.

These discussions have led to the development of this support program for
research on the development of methodology and technology for the constituent
tasks of structural genomics and the PSI. The scope of this PA includes all
the computational and experimental facets described above.  These applications
must directly address one or more of the constituent tasks of structural
genomics and lead to likely improvements in the efficiency of the subsequent
large scale program for structural determination in a high throughput mode.

Grantees in the PSI program will be expected to attend an annual meeting at
the NIH to discuss their progress and results.


The purpose of this SBIR/STTR program announcement is to stimulate research
projects on the development of methodology and technology related to
structural determinations in a high throughput mode and the other constituent
tasks of structural genomics.  This research is crucial for the subsequent
development of a structural genomics research program and a structural
inventory of proteins in living systems.

There are two other initiatives related to this one:

1.  A similar program for structural genomics methodology and technology
development for individual research project applications (R01) and program
project applications (P01).  This PA is available at:

2.  Projects to serve as pilots to examine the best approach to integrated PSI
(Structural Genomics) programs.  These applications should include all the
constituent parts of the overall PSI project.  These pilots will be supported
as research centers and the Request for Applications (RFA) for this program
was published on June 3, 1999.  The RFA is available at the following URL:


This PA must be read in conjunction with the Omnibus Solicitation of the
Public Health Service for Small Business Innovation Research (SBIR) Grant
Applications (PHS 99-2) and the Omnibus Solicitation of the National
Institutes of Health for Small Business Technology Transfer (STTR) Grant
Applications (PHS 99-3).  All of the instructions within the Omnibus
Solicitation apply.

Omnibus Solicitations for both the SBIR and STTR programs are available
electronically through the NIH, Office of Extramural Research "Small Business
Funding Opportunities" web site:

Hard copies, subject to availability, may be obtained from the PHS SBIR/STTR
Solicitation Office, phone (301) 206-9385; FAX (301) 206-9722; email  Helpful information in preparation of the application can be
obtained at: and

Applications in response to this PA are to be submitted on the grant
application form PHS 6246-1 (1/98) for SBIR Phase I
[], PHS 6246-3 (1/98) for STTR
Phase I [], PHS 6246-2 (1/98)
for SBIR Phase II [], and PHS
6246-4 (1/98) for STTR Phase II

The Phase I applications are also located in the back pages of the Omnibus

The title and number of this PA must be typed in line 2 on the face page of
the application.

Potential applicants are encouraged to contact program staff for guidance and
to read the advice and information on the web sites.  However, responsibility
for planning, direction, and execution of the proposed research will be solely
that of the applicant.

As stated in the MECHANISMS OF SUPPORT section, applications may be submitted
for Phase I alone (R41/43), or Phase II (R42/44) alone if there has been
previous and successful Phase I support, or through the FAST-TRACK mechanism. 
Application instructions specified in the Omnibus Solicitation for each
mechanism must be followed.

The normal level of support and period of time for a Phase I SBIR award is
$100,000 and six months; for a Phase II SBIR award, $750,000 and two years. 
The normal level of support and period of time for a Phase I STTR award is
$100,000 and one year; for a Phase II STTR award is $500,000 and two years. 
However, applicants may propose longer periods of time and greater amounts of
funds if necessary for completion of the project.  (See NIH Guide, February
12, 1998;

Phase I, FAST-TRACK applications must specify clear, measurable goals that
should be achieved prior to Phase II funding.  Failure to provide measurable
goals in sufficient detail in the Phase II application may be a reason for the
peer review committee to exclude the Phase II application from consideration.

Phase II applications submitted in response to this PA will only be accepted
as continuations of previously funded Phase I grants.  The Phase II proposal
must be a logical extension of the Phase I research but not necessarily a
Phase I supported in response to this PA.

The National Institutes of Health (NIH) is employing features of the Modular
Grant Application and Award procedures under its SBIR program.  SBIR Phase I
grant applications requesting up to $100,000 total costs (direct costs,
indirect costs, and fixed fee) will request direct costs in a budget narrative
format rather than being compiled from detailed and separate categories.

A summary of the unique features of the SBIR modular grant application and
award process can be found at  These features are
described in more detail within the SBIR Omnibus Solicitation (PHS 99-2, page
1).  Similarly, a summary of the unique features of the STTR modular grant
application and award process can be found at and are described in more
detail within the STTR Omnibus Solicitation (PHS 99-3, page 1).

For applications requesting in excess of $100,000 total costs (direct costs,
indirect costs, and fixed fee) the Modular Grant features do not apply.

The completed original application and one legible copy must be sent or
delivered to:

BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

Applications must be received by the receipt dates listed at the top of the
first page of this PA.


Upon receipt, applications will be reviewed by the Center for Scientific
Review (CSR) for completeness and by the NIH institutes for responsiveness. 
Applications not adhering to application instructions described above and
those applications that are incomplete or non-responsive will be returned to
the applicant without review.

Applications will be assigned on the basis of established NIH referral
guidelines.  Applications will be evaluated for scientific and technical merit
by an appropriate scientific review group convened in accordance with the
standard NIH peer review procedures.  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 applications under review, will be discussed, assigned a
priority score, and receive a second level review by the appropriate national
advisory council or board.

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.  Note that the application
does not need to be strong in all categories to be judged likely to have major
scientific impact and thus deserve a high priority score.  For example, an
investigator may propose to carry out important work that by its nature is not
innovative but is essential to move a field forward.

Review criteria are as described in the Omnibus Solicitation:

1.  The soundness and technical merit of the proposed approach.

2.  The qualifications of the proposed Principal Investigator, supporting
staff, and consultants.

3.  The scientific, technical, or technological innovation of the proposed

4.  The potential of the proposed research for commercial application.

5.  The appropriateness of the budget requested.

6.  The adequacy and suitability of the facilities and research environment.

7.  Where appropriate, the adequacy of assurances detailing the proposed means
for (a) safeguarding human or animal subjects and/or (b) protecting against or
minimizing any adverse effect on the environment.

The phase I application should specify clear, measurable goals (milestones)
that should be achieved prior to initiating Phase II.  Failure to provide
clear, measurable goals may be sufficient reason for the study section to
judge the application non-competitive.


Applications will compete for available funds with all other recommended SBIR
and STTR applications.  Funding decisions for Phase I or Phase II applications
will be based on quality of the proposed project as determined by peer review,
availability of funds, and program priority.  Particular attention will also
be given to whether or not the development of methods and technologies
described in the application are likely to increase high throughput structure
determination and provide the underpinning for structural genomics projects. 
In addition, the application must include plans for rapid dissemination of the
results, and, if applicable, rapid deposition and release of all protein
coordinates into the Protein Data Bank, i.e., holds on release are not

FAST-TRACK Phase II applications may be funded following submission of the
Phase I progress report and other documents necessary for continuation.  Phase
II applications will be selected for funding based on the initial priority
score, NIGMS' assessment of the Phase I progress and determination that Phase
I goals were achieved, the project's potential for commercial success, and the
availability of funds.


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

Maren R. Laughlin, Ph.D.
Director of Metabolism Program, DDEM, NIDDK
Natcher room 5AN-24J
45 Center Dr. MSC 6600
Bethesda, MD  20892-6600
Telephone: (310) 594-8802
FAX: (301) 480-3503

Carol H. Letendre, Ph.D.
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Suite 10142
Bethesda, MD  20892-7950
Telephone:  (301) 435-0080
FAX:  (301) 480-0867

Abraham Levy, Ph.D.
Biomedical Technology
National Center for Research Resources
6705 Rockledge Drive, Room 6150
Bethesda, MD  20892-7965
Telephone:  (301) 435-0755
FAX:  (301) 480-3659

Peter Clepper, Ph.D.
Program Officer
Extramural Programs
National Library of Medicine
Bethesda, MD 20894
Telephone: (301) 594-4882
FAX: (301) 402-2952

Direct inquiries regarding fiscal matters to:

Ms. Linda Roberts
Grants Management Office
National Institute of General Medical Sciences
45 Center Drive, Room 2AS.55E
Bethesda, MD  20892-6200
Telephone:  (301) 594-5141
FAX:  (301) 480-2554


This program is described in the Catalog of Federal Domestic Assistance No.
93.821 for NIGMS; No. 93.847 for NIDDK; Nos. 93.837, 93.838, and 93.839 for
NHLBI; No. 93.371 for NCRR; and 93.879 for NLM.  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 the NIH Grant Policy Statement (10/1/98) and Federal Regulations 42 CFR
52 and 45 CFR Part 74 and Part 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 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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