This Program Announcement expires on December 7, 2004, unless reissued.

PROBES FOR MICROIMAGING THE NERVOUS SYSTEM (SBIR AWARD)

Release Date:  December 5, 2001

PA NUMBER:  PA-02-029 (This PA has been reissued, see PA-05-120)

National Institute of Mental Health
 (http://www.nimh.nih.gov/)
National Institute on Deafness and Other Communication Disorders
 (http://www.nidcd.nih.gov/)
National Institute of Neurological Disorders and Stroke
 (http://www.ninds.nih.gov/)
National Institute on Aging
 (http://www.nia.nih.gov/)
National Institute of Biomedical Imaging and Bioengineering
 (http://www.nibib.nih.gov/)

PURPOSE

The National Institute of Mental Health (NIMH), National Institute on 
Deafness and Other Communication Disorders (NIDCD), National Institute on 
Neurological Disorders and Stroke (NINDS), National Institute on Aging (NIA), 
and National Institute of Biomedical Imaging and Bioengineering (NIBIB) 
invite grant applications for Small Business Innovation Research (SBIR) 
projects on research and development of probes useful in imaging the 
structure and function of the brain and other parts of the nervous system, 
with award duration and amounts greater than those routinely allowed under 
the SBIR program. Encouraged are applications from teams of investigators 
from commercial, academic and other sectors of the research community.  Non-
commercial partners, including those at colleges and universities, may play 
important roles in SBIR-supported research, and may receive substantial 
support for their efforts.

Specifically, this PA solicits SBIR grant applications that propose research 
and development of probes that generate signals detectable by one or more 
imaging modality.  Such probes should indicate the structure or function of 
molecules or subcellular elements of neurons or other cells of the nervous 
system.  Of special interest are applications that propose research and 
development of novel probes, although significant enhancements of already 
existing probes are also solicited.  Grant applications may propose projects 
that will result in probes solely intended for use in research or probes that 
might have clinical utility.

It is expected that this initiative will require expertise from a variety of 
disciplines, including neuroscience, biology, chemistry, physics, 
engineering, biotechnology, and bioengineering.  Moreover, it is anticipated 
that these types of expertise will be brought together in various 
combinations in individual proposed projects.

This PA must be read in conjunction with the Omnibus Solicitation of the NIH, 
CDC and FDA SBIR and STTR Grant Applications found at 
http://grants.nih.gov/grants/funding/sbir.htm, the instructions for Phase II 
Grant Applications found at http://grants.nih.gov/grants/funding/sbir2/index.htm 
and the PHS 398 Instructions 
(http://grants.nih.gov/grants/funding/phs398/phs398.html).  Except as noted 
below, all instructions and information in these documents also apply to 
applications submitted in response to this PA.

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 PA, Probes For 
Microimaging The Nervous System (SBIR Award) is related to one or more of the 
priority areas.  Potential applicants may obtain a copy of "Healthy People 
2010" at http://www.health.gov/healthypeople/.

ELIGIBILITY REQUIREMENTS

Eligibility requirements for Phase I and Phase II grants are found at 
http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf and 
http://grants.nih.gov/grants/funding/sbir2/index.htm, respectively. 

MECHANISM OF SUPPORT-PHASE I

Phase I applications in response to this PA will be funded as Phase I 
SBIR Grants (R43) with modifications as described below. Responsibility 
for the planning, direction, and execution of the proposed research will be 
solely that of the applicant.  Applications for Phase I grants should be 
prepared following the instructions at 
http://grants.nih.gov/grants/funding/phs398/phs398.html.

o  Project Period and Amount of Award.

Because the length of time and cost of research and development of 
microimaging probes often exceed those routinely awarded for SBIR grants, a 
project period up to two years and a budget not to exceed a total cost of 
$250,000 per year (direct costs, indirect costs and fixed fee) will be 
considered under this PA if the time period and amount are well justified.  
See section, BUDGET REQUESTS GREATER THAN $100,000 TOTAL COSTS, in 
http://grants.nih.gov/grants/funding/phs398/phs398.html for instructions on 
submitting a budget greater than $100,000.

o  Consultant and contractual costs.

The total amount of all consultant costs and contractual costs normally 
may not exceed 33% of the total costs requested for Phase I SBIR 
applications.  However, Phase I grant applications submitted under this PA 
may exceed this limit when well justified and when those costs are necessary 
to support clinical studies or trials.

MECHANISM OF SUPPORT - PHASE II

Phase II applications in response to this PA will be awarded as Phase II SBIR 
grants (R44) with modifications as described below.  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 previously funded Phase 
I award need not have been submitted in response to this PA, but the Phase II 
proposal must be a logical extension of the Phase I research.

Phase II applications should be prepared using instructions at 
http://grants.nih.gov/grants/funding/phs398/phs398.html.

o  Project Period and Amount of Award.

Because the length of time and cost of research and development of 
microimaging probes often exceed those routinely awarded for SBIR grants, a 
project period up to three years and a budget not to exceed total costs of 
$450,000 per year (direct costs, indirect costs and fixed fee) will be 
considered under this PA if the time period and amount are well justified.

o  Consultant and contractual costs.

The total amount of all consultant costs and contractual costs normally 
may not exceed 50% of the total costs requested for Phase II SBIR 
applications.  However, Phase II grant applications submitted under this PA 
may exceed this limit when well justified and when those costs are necessary 
to support clinical studies or trials.

MECHANISM OF SUPPORT-FAST TRACK

Applications for Fast Track SBIR grants should be prepared following the 
instructions for Phase I and Phase II applications at 
http://grants.nih.gov/grants/funding/phs398/phs398.html.  And the additional 
instructions at http://grants.nih.gov/grants/funding/sbirsttr1/sbirsttrft-rs.pdf.

The total duration of Phase I and Phase II cannot exceed 5 years for fast 
track applications, and the budget levels described above for Phase I and 
Phase II applications apply.

RESEARCH OBJECTIVES 

Background 

An emerging area of scientific opportunity is the design and use of probes to 
study structure and function at the molecular and subcellular level in living 
cells.  Approaches and tools such as labels that attach to specific peptide 
or nucleotide moieties, Fluorescent Resonance Energy Transfer, Green 
Fluorescent Protein (and mutant color variants), and genetically-engineered 
voltage or ion-sensitive fluorophores are making it possible to begin to 
visualize not only the distribution of molecular species in cells, but the 
manner in which they interact.

Research and development of these, and other such technologies, hold the 
promise of providing scientists the capabilities to track the ebb and flow of 
signal transduction cascades, protein-protein interactions, protein-
nucleotide interactions, movement of subcellular elements within cells, and 
other dynamic events.  And, it appears that as such tools are elaborated and 
further studied, they will permit such observations to be quantitative and 
made in real time.  Finally, bioengineering individual probes that are 
detectable by multiple modalities, (e.g., electron microscopy, fluorescent 
microscopy and fluorescent spectroscopy, magnetic resonance imaging) would 
add great value by allowing independent lines of scientific inquiry to 
converge on the same cellular process and/or structure as indicated by the 
multimodal probe.

This area of science and technology is poised for major advances, and these 
advances would bring new levels of understanding of the molecular physiology 
of nervous system cells, as well as the manner in which this physiology is 
affected by disease, pharmacologic agents, development, etc. 

Research Topics

Examples of general research topics that would be considered responsive to 
this PA are listed below.  This is not meant to be an exhaustive, exclusive 
or delimiting set of topics.  Rather these represent illustrations of 
projects that would be considered relevant to this PA.

o  Bioengineering of small-molecule, sterically benign probes that can be 
genetically linked to proteins that play important roles in cell function

o  Research, development and engineering of probes that can report 
quantitative information regarding particular molecular or subcellular events 
or structures

o  Research and development of probes that attach to specific sites on 
proteins which are observable through multiple modalities.

o  Research and development of caged molecules that provide temporally and 
spatially controlled release of molecular probes 

Finally, although the mission of the National Institute of Biomedical Imaging 
and Bioengineering (NIBIB) does not focus on probes used primarily to study a 
single organ system, such as the brain, NIBIB is very interested in 
supporting more fundamental work on design and use of probes to study 
structure and function at the molecular and subcellular level in living cells
used across multiple modalities and multiple organ systems.

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 clinical research 
projects unless a clear and compelling justification is 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 clinical research should read the AMENDMENT "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research - Amended, October, 2001," published in the NIH Guide for Grants and 
Contracts on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html), 
a complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.  
The amended policy incorporates: the use of an NIH definition of 
clinical research, updated racial and ethnic categories in compliance with 
the new OMB standards, clarification of language governing NIH-defined Phase 
III clinical trials consistent with the new PHS Form 398, and updated roles 
and responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must 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 b) investigators must report annual accrual and progress in conducting 
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.

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS

NIH policy requires education on the protection of human subject participants 
for all investigators submitting NIH proposals for research involving human 
subjects.  This policy announcement is found in the NIH Guide for Grants and 
Contracts Announcement dated June 5, 2000, at the following website: 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

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.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT

The Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) 
cited publicly and officially by a Federal agency in support of an action 
that has the force and effect of law (i.e., a regulation) may be accessed 
through FOIA.  It is important for applicants to understand the basic scope 
of this amendment.  NIH has provided guidance at  
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application.  In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

APPLICATION PROCEDURES

Applicants should follow the instructions for SBIR Phase I, Phase II or 
fast-track submissions with the modifications as noted in this PA.

The original application and five single-sided copies must be mailed to 
the NIH Center for Scientific Review.  For purposes of identification 
and processing, the title and number of this PA must be shown in the 
appropriate place on the face page of the SBIR Phase I or Phase II 
applications.  Follow the mailing instructions in the Omnibus Solicitation 
for Phase I applications.  Follow the mailing instructions in the Phase II 
application package for Phase II applications.

Applicants are encouraged to contact the program staff listed under INQUIRIES 
with any questions regarding their proposed project and the goals of this PA.

REVIEW CONSIDERATIONS

Applications will be assigned on the basis of established PHS 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

Review criteria are described in Phase I and Phase II SBIR websites listed 
above.  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.

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o  scientific merit (as determined by peer review)
o  availability of funds
o  programmatic priorities

INQUIRIES

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

Direct inquiries regarding programmatic issues to:

Margaret Grabb, Ph.D.
Division of Basic and Clinical Neuroscience Research
National Institute of Mental Health
6001 Executive Boulevard, Room 7201, MSC 9645
Bethesda, MD  20892-9645
Rockville, MD  20852 (for express or courier service)
Telephone:  (301) 443-3563  
FAX:  (301) 443-1731
Email:  mgrabb@mail.nih.gov

Lynn Luethke, Ph.D.
Division of Extramural Research
National Institute on Deafness and Other Communication Disorders
6120 Executive Boulevard, Room 400-C, MSC 7180
Bethesda, MD  20892-7180
Telephone:  (301) 402-3458
FAX:  (301) 402-6251
Email:  lynn_luethke@nih.gov

Thomas Miller, Ph.D.
Technology Development
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard, Room 2139
Bethesda, MD  20892
Telephone:  (301) 496-1779
FAX:  (301) 402-1501
Email:  tm208y@nih.gov

Bradley C. Wise, Ph.D.
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging
7201 Wisconsin Avenue, Suite 3C07, MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-9350
FAX:  (301) 496-1494
Email:  wiseb@nia.nih.gov

Richard E. Swaja, Ph.D.
Division of Biomedical Imaging
National Institute of Biomedical Imaging and Bioengineering
31 Center Drive, Room 1B37
Bethesda, MD  20892-2077
Telephone:  (301) 451-6771
FAX:  (301) 480-4515
Email:  swajar@nibib.nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Kathy Hancock
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17M
Bethesda, MD  20892-7510
Telephone:  (301) 496-5482
FAX:  (301) 402-0915
Email:  hancockk@mail.nih.gov

Ms. Sara Stone
Grants Management Branch
National Institute on Deafness and Other Communication Disorders
6120 Executive Boulevard, Room 400B, MSC-7180
Bethesda, MD  20892 
Telephone:  (301) 402-0909
FAX:  (301) 402-1758
Email:  stones@nidcd.nih.gov

Ms. Rebecca Claycamp, CRA
Deputy Grants Management Officer
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard, Room 3258
Bethesda, MD  20892
Telephone:  (301) 496-9231
FAX:  (301) 402-0219
Email:  rc253d@nih.gov

Ms. Linda Whipp
Grants and Contracts Management Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2N212, MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-1472
FAX:  (301) 496-3672
Email:  WhippL@nia.nih.gov

Annette Hanopole, CRA
Grants Management Branch
National Institute of Biomedical Imaging and Bioengineering
31 Center Drive, Room 1B37
Bethesda, MD  20892-2077
Telephone:  (301)451-6768
FAX:  (301) 480-4515
Email:  Hanopola@mail.nih.gov

AUTHORITY AND REGULATIONS 

This program is described in the Catalog of Federal Domestic Assistance No. 
93.242 (NIMH), 93.847 (NIDCD), 93.853 (NINDS), 93.866 (NIA), and 93.286 
(NIBIB).  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 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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