[Federal Register Volume 66, Number 6 (Tuesday, January 9, 2001)]
[Notices]
[Pages 1650-1653]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-586]


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DEPARTMENT OF ENERGY


Office of Science; Office of Science Financial Assistance Program 
Notice 01-17; Low Dose Radiation Research Program--Pilot Modeling 
Projects

AGENCY: Department of Energy.

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 applications for research that 
supports the Low Dose Radiation Research Program. Research is 
specifically sought for pilot projects that involve innovative 
collaborations between experimentalists and modelers to:
     Model the mechanisms of key radiation-induced biological 
responses.
     To describe or identify strategies for developing 
biologically-based risk models that incorporate information on 
mechanisms of radiation-induced biological responses.
    The Low Dose Radiation Research Program uses modern molecular tools 
to develop a better scientific basis for understanding exposures and 
risks to humans from low dose radiation that can be used to achieve 
acceptable levels of human health protection at a reasonable cost.

DATES: Potential applicants should submit a one page preapplication 
referencing Program Notice 01-17 by 4:30 p.m. e.s.t., February 1, 2001. 
Receipt of preapplications sent by e-mail will be acknowledged by a 
return message. An email response to preapplications discussing the 
potential program relevance of a formal application generally will be 
communicated by February 8, 2001.
    The deadline for receipt of formal applications is 4:30 p.m., 
e.s.t., May 1, 2001, in order to be accepted for merit review and to 
permit timely consideration for award in FY 2001 and FY 2002.

ADDRESSES: Preapplications referencing Program Notice 01-17, should be 
sent by E-mail to [email protected]. Preapplications will 
also be accepted if mailed to the following address: Ms. Joanne 
Corcoran, Office of Biological and Environmental Research, SC-72, U.S. 
Department of Energy, 19901 Germantown Road, Germantown, MD 20874-1290.
    Formal applications, referencing Program Notice 01-17, should be 
sent 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 01-17. This address also must be used when 
submitting applications by U.S. Postal Service Express, commercial mail 
delivery service, or when hand carried by the applicant.

FOR FURTHER INFORMATION CONTACT: Dr. David Thomassen, telephone: (301) 
903-9817, E-mail: [email protected], Office of Biological 
and Environmental Research, SC-72, U.S. Department of Energy, 19901 
Germantown Road, Germantown, MD 20874-1290. The full text of Program 
Notice 01-17 is available via the World Wide Web using the following 
web site address: http://www.sc.doe.gov/production/grants/grants.html.

SUPPLEMENTARY INFORMATION: Low Dose Radiation Research Program
    Background information on the Low Dose Radiation Research Program 
can be found in the research program plan at http://www.lowdose.org/index.html. A list of currently funded projects can be found at http://lowdose.org/research.html. A parallel request for research applications 
focused on understanding the biological responses to low doses of low 
LET ionizing radiation and on genetic factors influencing those 
responses has been issued (Office of Science Notice 01-18).
    This research program is faced with the challenge of conducting 
research that can be used to inform the development of future radiation 
risk policy. Not all research on the biological effects of low doses of 
radiation will be equally useful for the development of radiation risk 
policy though the path from basic radiation biology research to 
radiation risk policy is admittedly not clear at this time.
    Information on biological responses to low doses of radiation will 
most likely have an impact on radiation risk policy through its 
incorporation into biologically-based models for radiation risk. Two 
types of models will be important in efforts to incorporate results 
from current low dose radiation research into radiation risk policy: 
mechanistic models and biologically-based risk models.
    Mechanistic models are defined as mathematical descriptions of the 
molecular and cellular processes involved in biological responses to 
radiation. One goal for these types of models will be to develop 
predictive capabilities for the range and nature of biological 
responses expected in a given system following exposure to different 
doses of radiation. The ability to extrapolate between different levels 
of biological organization (from molecules to cells to tissues to 
organisms) and from observations in vitro to biological responses in 
vivo should be improved by the development of such models.
    Biologically-based risk models are defined as mathematical 
constructs of the key events involved in the production of an adverse 
health effect, e.g., cancer, in response to radiation across a range of 
doses of interest. Such models are likely to describe both continuous 
and probabilistic variables that range from key molecular probabilities 
of inducing cell death, replication or specific gene expression to 
modifiers of responses at the tissue level or even at the level of the 
entire organism. Mathematical predictors or estimators of radiation 
risk can include both epidemiological and experimental information. One 
likely source of input for the development and use of biologically-
based risk models is mechanistic models for radiation-induced 
biological responses. For example, if a mechanistic model for the 
induction of a by-stander effect by low doses of radiation existed, 
information from that model could, in theory, serve as a direct source 
of information on an ``effective radiation dose'' in a biologically-
based risk model.

Pilot Projects

    Pilot, collaborative research projects are requested in one of two 
areas:
     Pilot projects to model the mechanisms of key radiation-
induced biological responses.
     Pilot projects to describe or identify strategies for 
developing biologically-based risk models that incorporate information 
on mechanisms of radiation-induced biological responses.
    Projects will involve research teams that include both laboratory-
based scientists and scientists whose expertise is in the development 
or use of mathematical models. Projects can range from active research-
modeling efforts to more ``think tank'' type efforts. Experimentalists 
and modelers are encouraged to interact in an iterative process of 
experimentation and modeling to generate and identify hypotheses, data 
and both experimental and modeling needs that then drive the ``next 
steps'' of both laboratory and modeling experiments. Alternatively, 
experimentalists and modelers could interact to identify research and 
modeling needs and gaps that are barriers to the development of true 
biologically-based risk models, to develop ``what-if'' type scenarios 
describing how different types of biological data could and would be 
used in these models and to identify new modeling strategies that take 
into account a broader range of biological information on radiation 
responses.
    Modeling mechanisms of key radiation-induced biological responses. 
Mechanistic models can and should be developed for a range of 
biological responses that meet the Criteria for Selection of Biological 
Responses

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described below. This portion of the program has two goals: (1) To 
develop models that have the potential to serve as links between data 
describing molecular and cellular responses to radiation and the use of 
that data in biologically-based risk models; and (2) To develop 
predictive capabilities for the range and nature of biological 
responses expected in a given system following exposure to different 
doses of radiation. It is expected that collaborations in this area 
will involve an iterative process of experimentation, modeling, 
experimentation, etc. Models of experimental data should be developed 
and used to make predictions about biological responses or effects that 
are then tested experimentally.
    Description or identification of strategies to develop 
biologically-based risk models that incorporate information on 
mechanisms of radiation-induced biological responses. In many or most 
cases there may be such a wide gap between the nature of biological 
data and the state of risk models that it is premature, if not 
impossible, to begin incorporating biological data into these models. 
Research in this area will focus more on ``think tank'' types of 
activities to identify how information on biological responses to low 
doses of radiation could, conceptually, be incorporated into risk 
models. Investigators should use their knowledge of biology and 
modeling to develop realistic scenarios for the development of 
biologically-based risk models where neither current biological 
information nor modeling capabilities are adequate to actually develop 
these models. This research will follow a ``what if'' or ``if only'' 
type of approach where the use of theoretically obtainable but 
currently unavailable biological data is described for risk models that 
have not yet been developed. These pilot activities should have as 
their goal the identification of key experiments that would serve to 
verify key hypotheses that are generated or the preliminary design for 
incorporating these parameters into biologically-based risk models. 
Researchers might organize workshops to obtain some of the information 
needed to carry out their study. Pilots in this area will ordinarily be 
limited to 1-2 years. Successful or promising pilots will be eligible 
for additional funds to validate key hypotheses or to expand the scope 
of the research that was originally proposed. It is not the intent of 
this solicitation to fund the complete development of new biologically-
based risk models that incorporate information on mechanisms of 
radiation-induced biological responses since it is our belief that it 
is premature to attempt to develop such models at this time.

Criteria for Selection of Biological Responses

    It is our belief that the most useful research will focus on 
biological responses that meet each of the following criteria. The 
biological responses of greatest interest for this solicitation include 
bystander effects, induction of genetic instability and adaptive 
responses. Applications proposing the use of additional biological 
responses will be considered only if the biological responses proposed 
for investigation can be reasonably demonstrated to meet the criteria 
outlined below.
     Are known to be induced at low doses of radiation.
     Have the potential to increase or decrease the biological 
effects of radiation if they occur at low doses of radiation.
     Have the potential to directly impact, i.e., increase or 
decrease, the subsequent development of cancer or other harmful health 
impacts.
     Are potentially quantifiable.
     Could, potentially, be linked to the development of a 
biologically-based model for radiation risk.
    Alternatively, a biological response of interest could meet all of 
the above criteria only at high doses but may actually not be induced 
(not simply undetectable) at low doses of radiation. Since the 
mechanisms of action may be different after high versus low doses of 
radiation, such studies would help define these mechanisms. Defining 
the unique doses where these mechanisms shift is important for 
comparing, understanding and modeling biological responses to high 
versus low doses of radiation.

Program Funding

    It is anticipated that up to $750,000 will be available for new 
grant awards during FY 2001 and FY 2002, contingent upon the 
availability of funds. Multiple year funding of grant awards is 
expected, and is also contingent upon the availability of appropriated 
funds, progress of the research, and continuing program need. It is 
expected that most awards will be from 1 to 3 years and will range from 
$100,000 to $250,000 per year (total costs).

Collaboration

    Applicants are encouraged to collaborate with researchers in other 
institutions, such as universities, industry, non-profit organizations, 
federal laboratories and Federally Funded Research and Development 
Centers (FFRDCs), including the DOE National Laboratories, where 
appropriate, and to incorporate cost sharing and/or consortia wherever 
feasible.

Preapplication

    A preapplication should be submitted. The preapplication should 
contain a title, list of investigators, address, telephone, fax and E-
mail address of the Principal Investigator, and no more than a one page 
summary of the proposed research, including project objectives and 
methods of accomplishment. Responses to the preapplications, 
encouraging or discouraging formal applications, will generally be 
communicated within 7 days of receipt. Notification of a successful 
preapplication is not an indication that an award will be made in 
response to the formal application.

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 Department's programmatic needs. 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.

Applications

    Note: Please Note Critical Information Below on Page Limits.

    Information about the development and submission of applications, 
eligibility, limitations, evaluation, selection process, and other 
policies and procedures may be found in the Application Guide for the 
Office of Science Financial Assistance Program and 10 CFR Part 605. 
Electronic access to the Guide and required forms is made

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available via the World Wide Web at: http://www.er.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.
    The Project Description must be 25 pages or less, exclusive of 
attachments. Applications with Project Descriptions longer than 25 
pages will be returned to applicants and will not be reviewed. The 
application must contain an abstract or project summary, letters of 
intent from collaborators, and short curriculum vitaes consistent with 
NIH guidelines.
    Adherence to type size and line spacing requirements is necessary 
for several reasons. No applicants should have the advantage, or by 
using small type, of providing more text in their applications. Small 
type may also make it difficult for reviewers to read the application. 
Applications must have 1-inch margins at the top, bottom, and on each 
side. Type sizes must be 10 point or larger. Line spacing is at the 
discretion of the applicant but there must be no more than 6 lines per 
vertical inch of text. Pages should be standard 8 \1/2\"  x  11" (or 
metric A4, i.e., 210 mm  x  297 mm).
    Applicants are expected to use the following ordered format to 
prepare applications in addition to following instructions in the 
Application Guide for the Office of Science Financial Assistance 
Program. Applications must be written in English, with all budgets in 
U.S. dollars.
     Face Page (DOE F 4650.2 (10-91)).
     Project Abstract (no more than one page).
     Budgets for each year and a summary budget page for the 
entire project period (using DOE F 4620.1).
     Budget Explanation.
     Budgets and Budget explanation for each collaborative 
subproject, if any.
     Project Description (The Project Description must be 25 
pages or less, exclusive of attachments. Applications with Project 
Descriptions longer than 25 pages will be returned to applicants and 
will not be reviewed.)
     Goals.
     Background.
     Research Plan.
     Preliminary Studies and progress (if applicable).
     Research Design and Methodologies.
     Literature Cited.
     Collaborative Arrangements (if applicable).
     Biographical Sketches (limit 2 pages per senior 
investigator).
     Description of Facilities and Resources.
     Current and Pending Support for each senior investigator.
    The Office of Science, as part of its grant regulations, requires 
at 10 CFR 605.11(b) that a recipient receiving a grant to perform 
research involving recombinant DNA molecules and/or organisms and 
viruses containing recombinant DNA molecules shall comply with the 
National Institutes of Health ``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 December 29, 2000.
Ralph H. De Lorenzo,
Acting Associate Director of Science for Resource Management.
[FR Doc. 01-586 Filed 1-8-01; 8:45 am]
BILLING CODE 6450-01-P