[Federal Register Volume 65, Number 53 (Friday, March 17, 2000)]
[Notices]
[Pages 14549-14551]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-6654]


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DEPARTMENT OF ENERGY


Office of Science Financial Assistance Program Notice 00-13; 
Medical Applications Program

AGENCY: Department of Energy (DOE).

ACTION: Notice inviting grant applications.

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SUMMARY: The Office of Biological and Environmental Research (OBER) of 
the Office of Science (SC), U.S. Department of Energy (DOE), hereby 
announces its interest in receiving grant applications to support one 
specific research area within the Medical Applications Program: Imaging 
Gene Expression in Health and Disease. The specific goals include 
development of nuclear medicine driven technologies to image mRNA 
transcripts in real time in tissue culture and whole animals. Special 
consideration will be given to applications arising from a well 
integrated, multidisciplinary team effort of scientists with skills to 
address the needs, issues and importance of nucleic acid biochemistry, 
radioligand synthesis and macromolecular interactions; functional 
consequences of gene expression by targeting and perturbing the 
activity of a particular gene; and biological applications of optical 
and radionuclide imaging devices; contributing to the goal of imaging 
specific gene expression in real time in animals to humans. The access 
to, or availability of specialized molecular radioligands, transgenic 
animal models of human disease, and biological imaging devices for real 
time imaging in animals to humans, will be important factors for 
funding considerations. Methodological approaches that are applicable 
to any mRNA species are encouraged.

DATES: Before preparing a formal application, potential applicants are 
encouraged to submit a brief preapplication. All preapplications 
referencing Program Notice 00-13, should be received by DOE by 4:30 pm, 
EDT., April 14, 2000. A response encouraging or discouraging the 
submission of a formal application will be communicated by electronic 
mail by April 21, 2000.
    Formal applications submitted in response to this notice must be 
received by 4:30 p.m., E.D.T., May 30, 2000, to be accepted for merit 
review and consideration for award in Fiscal Years 2000 and 2001.

ADDRESSES: Preapplications referencing Program Notice 00-13, must be 
sent by E-mail to [email protected]. Preapplications will 
also be accepted if mailed to the following address: Ms. Sharon Betson, 
Office of Biological and Environmental Research, SC-73, 19901 
Germantown Road, Germantown, MD 20874-1290.
    Formal applications referencing Program Notice 00-13, should be 
forwarded to: U.S. Department of Energy, Office of Science, Grants and 
Contracts Division, SC-64, 19901 Germantown Road, Germantown, MD 20874-
1290, ATTN: Program Notice 00-13. This address must also be used when 
submitting applications by U.S. Postal Service Express Mail or any 
other commercial overnight delivery service, or hand-carried by the 
applicant. An original and seven copies of the application must be 
submitted.

FOR FURTHER INFORMATION CONTACT: Dr. Prem C. Srivastava, Office of 
Biological and Environmental Research, Medical Sciences Division (SC-
73), U.S. Department of Energy, 19901 Germantown Road, Germantown, MD 
20874-1290, telephone: (301) 903-4071, FAX: (301) 903-0567, E-mail: 
[email protected]. The full text of Program Notice 00-13 
is available via the Internet using the following web site address: 
http://www.sc.doe.gov/production/grants/grants.html.

SUPPLEMENTARY INFORMATION: The Medical Applications Program supports 
directed nuclear medicine research through radiopharmaceutical 
development, molecular nuclear medicine and medical imaging 
instrumentation program activities to study uses of radioisotopes for 
non-invasive diagnosis and internal molecular radiotherapy. Molecules 
directing or affected by homeostatic controls always interact and, 
thus, are targets for specific molecular substrates. The substrate 
molecules can be tailored to fulfil a specific need and labeled with 
appropriate radioisotopes to become measurable in real time in the body 
on their way to, and in interaction with their targets allowing the 
analysis of molecular function in homeostatic control in health and 
disease. The function of radiopharmaceuticals at various sites in the 
body is imaged by nuclear medical instruments, such as, gamma cameras 
and positron emission tomographs (PET). This type of imaging refines 
diagnostic differentiation at molecular/metabolic levels between health 
and disease, and among various diseases such as of the heart, brain and 
cancer, often leading to more effective therapy. If labeled with high 
energy-emitting radioisotopes, the substrate molecules, carrying the 
radiation dose

[[Page 14550]]

may be powerful tools for targeted molecular therapy especially of 
cancer.
    Basic research in molecular biology has provided new insights to 
the molecular basis of disease and molecular targets of human diseases. 
The current Molecular Nuclear Medicine program encourages development 
of new technologies for molecular delivery of radioisotopes to the 
disease-target-sites with a high degree of molecular precision, 
recognition, and target selectivity.
    In addition nuclear medicine, with the availability of miniaturized 
PET technology for small animal imaging, can facilitate mapping of the 
biochemistry of the metabolic organ function, visualizing the molecular 
biology of cell function, and zooming in on gene function for 
delineating differences in molecular biology of normal health from 
disease, in animals to humans.
    With the advent of the genome project and the development of 
transgenic mice, there has been a rapid proliferation of small animal 
models of human diseases, and improvement in optical and radionuclide 
in vivo imaging instrumentation technologies. These technological 
advancements have offered a paradigm shift in the current level of 
nuclear medicine research challenges and opportunities. Nuclear 
medicine techniques can permit analysis of the molecular elements as 
markers of genetic manipulations, biological transformations and 
progression of the disease, and provide insights to molecular pathways 
of disease and gene function. The development of generic methods to 
image specific gene expression will result in major advances in our 
understanding of developmental biology, cancer induction and 
pathogenesis, and in the clinical detection of inherited and acquired 
diseases. Such studies are therefore a major focus of this program. 
Additional information can be obtained at the following web site http:/
/www.sc.doe.gov/production/ober/msd__reports.html.
    This Notice is to solicit applications for grants for imaging gene 
expression in real time, in tissue culture and in whole animals in 
vivo. Currently the expression of endogenous genes in animals 
(including humans) cannot be imaged, at least not directly. Given the 
astounding pace of biotechnology development, it may be highly 
challenging but not an unattainable goal. A well integrated concerted 
team effort from the overlapping disciplines of chemistry and 
radiopharmaceutical chemistry, cellular and molecular biology, and 
biological and nuclear medicine imaging will become increasingly 
important for success. It will be important for each application to 
address response in view of the following research areas, which may be 
crucial for progress in imaging gene expression:
    (1) The radioligand molecules that will interact with the 
macromolecular nucleic acid structures in vivo. For example, the 
advances in antisense drug discovery means that antisense 
radiopharmaceuticals through combinatorial chemistry techniques can be 
designed to hybridize to target transcripts in a highly specific way. 
However, the antisense and combinatorial molecular chemistry 
technologies available for chemotherapeutic drug development, must be 
fully exploited and optimized for in vivo imaging.
    (2) Molecular signal amplification methods are not yet available 
that work in vivo at the mRNA level, and technological advancement in 
this area is well desired.
    (3) Equally important is the hurdle of drug targeting technology, 
which must be developed to such an extent that the various biological 
barriers can be safely surmounted in vivo.
    (4) Finally, the fluorescent molecular imaging technologies 
available for more routine in vitro screening and in vivo real time 
imaging, that can be used as a proof of principle and a prelude to in 
vivo nuclear medicine imaging, should be exploited in conjunction with 
nuclear medicine devices.

Program Funding

    It is anticipated that approximately $3 million will be available 
for multiple grant awards during Fiscal Years 2000 and 2001 contingent 
upon the availability of appropriated funds. Previous awards have 
ranged from $200,000 per year up to $400,000 per year (direct plus 
indirect costs) with terms lasting up to three years. Similar award 
sizes are anticipated for new grants. Applications may request project 
support up to three years, with out-year support contingent on the 
availability of funds, progress of the research and programmatic needs.

Preapplications

    A brief preapplication should be submitted. The preapplication 
should identify, on the cover sheet, the title of the project, the 
institution, principal investigator name, address, telephone, fax, and 
E-mail address. The preapplication should consist of two to three pages 
identifying and describing the research objectives, methods for 
accomplishment, and the key members of the scientific team responsible 
for undertaking this effort. Preapplications will be evaluated relative 
to the scope and research needs for the Imaging Gene Expression 
Program.

Merit Review

    Applications will be subjected to scientific merit review (peer 
review) and will be evaluated against the following evaluation criteria 
listed in descending order of importance as codified at 10 CFR 
605.10(d):

1. Scientific and/or Technical Merit of the Project
2. Appropriateness of the Proposed Method or Approach
3. Competency of Applicant's Personnel and Adequacy of Proposed 
Resources
4. Reasonableness and Appropriateness of the Proposed Budget.

The evaluation will include program policy factors such as the 
relevance of the proposed research to the terms of the announcement and 
the agency's programmatic needs. Note, external peer reviewers are 
selected with regard to both their scientific expertise and the absence 
of conflict-of-interest issues. Non-federal reviewers may be used, and 
submission of an application constitutes agreement that this is 
acceptable to the investigator(s) and the submitting institution.

Submission Information

    Information about the development, submission of applications, 
eligibility, limitations, evaluation, the selection process, and other 
policies and procedures may be found in 10 CFR Part 605, and in the 
Application Guide for the Office of Science Financial Assistance 
Program. Electronic access to the Guide and required forms is made 
available via the World Wide Web at: http://www.sc.doe.gov/production/grants/grants.html. DOE is under no obligation to pay for any costs 
associated with the preparation or submission of applications if an 
award is not made.
    In addition, for this Notice, the Project Description must be 25 
pages or less, exclusive of attachments, and the application must 
contain a Table of Contents, an abstract or project summary, letters of 
intent from collaborators (if any), and short curriculum vitae 
consistent with National Institutes of Health guidelines. On the SC 
grant face page, form DOE F4650.2, in block 15, also provide the PI's 
phone number, fax number, and E-mail address.
    DOE policy requires that potential applicants adhere to 10 CFR 745

[[Page 14551]]

``Protection of Human Subjects'', or such later revision of those 
guidelines as may be published in the Federal Register.
    The Office of Science as part of its grant regulations requires at 
10 CFR 605.11(b) that a recipient receiving a grant and performing 
research involving recombinant DNA molecules and/or organisms and 
viruses containing recombinant DNA molecules shall comply with NIH 
``Guidelines for Research Involving Recombinant DNA Molecules,'' which 
is available via the world wide web at: http://www.niehs.nih.gov/odhsb/biosafe/nih/rdna-apr98.pdf, (59 FR 34496, July 5, 1994,) or such later 
revision of those guidelines as may be published in the Federal 
Register.

    The Catalog of Federal Domestic Assistance Number for this 
program is 81.049, and the solicitation control number is ERFAP 10 
CFR Part 605.

    Issued in Washington, DC on March 9, 2000.
John Rodney Clark,
Associate Director of Science for Resource Management.
[FR Doc. 00-6654 Filed 3-16-00; 8:45 am]
BILLING CODE 6450-01-U