[Federal Register Volume 68, Number 33 (Wednesday, February 19, 2003)]
[Notices]
[Pages 7988-7989]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-3939]



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DEPARTMENT OF ENERGY


Office of Science Financial Assistance Program Notice 03-20; Low 
Dose Radiation Research Program--Biologically-Based Risk Modeling

AGENCY: Department of Energy.

ACTION: Notice inviting 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 participation in a 
biologically-based risk modeling exercise, for the purposes of 
developing and evaluating different modeling/prediction strategies. 
Awardees will be asked to develop individual biologically-based models 
incorporating one or more phenomena such as adaptive response, 
bystander effects, genetic susceptibility, or genomic instability. A 
central aspect of this exercise will be the eventual modeling, by all 
awardees, of an artificially defined biological test system or 
archetype having a set of biological characteristics and radiation-
induced endpoints for which exact probability values are either known 
or assigned. Please review the Supplementary Information and 
Application sections below for further details.

DATES: Preapplications (letters of intent) should be submitted by April 
4, 2003. Formal applications are due 4:30 p.m. EDT, May 23, 2003, in 
order to be accepted for merit review and to permit timely 
consideration for award in Fiscal Year 2003.

ADDRESSES: Preapplications referencing Program Notice 03-20, should be 
sent to Ms. Joanne Corcoran by E-mail: [email protected], 
with a copy to Dr. Noelle Metting at: [email protected].
    Formal applications referencing Program Notice 03-20 must be sent 
electronically by an authorized institutional business official through 
DOE's Industry Interactive Procurement System (IIPS) at: http://e-center.doe.gov (see also http://www.sc.doe.gov/production/grants/grants.html). IIPS provides for the posting of solicitations and 
receipt of applications in a paperless environment via the Internet. In 
order to submit applications through IIPS your business official will 
need to register at the IIPS website. The Office of Science will 
include attachments as part of this notice that provide the appropriate 
forms in PDF fillable format that are to be submitted through IIPS. 
Color images should be submitted in IIPS as a separate file in PDF 
format and identified as such. These images should be kept to a minimum 
due to the limitations of reproducing them. They should be numbered and 
referred to in the body of the technical scientific application as 
Color image 1, Color image 2, etc. Questions regarding the operation of 
IIPS may be E-mailed to the IIPS Help Desk at: [email protected], or 
you may call the help desk at: (800) 683-0751. Further information on 
the use of IIPS by the Office of Science is available at: http://www.sc.doe.gov/production/grants/grants.html.
    If you are unable to submit the application through IIPS, please 
contact the Grants and Contracts Division, Office of Science at: (301) 
903-5212, in order to gain assistance for submission through IIPS or to 
receive special approval and instruction on how to submit printed 
applications.

FOR FURTHER INFORMATION CONTACT: Dr. Noelle Metting, telephone: (301) 
903-8309, E-mail: [email protected], Office of Biological 
and Environmental Research, U.S. Department of Energy, SC-72/Germantown 
Building, 1000 Independence Avenue, SW., Washington, DC 20585-1290.

SUPPLEMENTARY INFORMATION: The Low Dose Radiation Research Program has 
the challenge of conducting research that can be used to inform the 
development of future national radiation risk policy for the public and 
the workplace. The Program has focused on quantifying and understanding 
the mechanisms of molecular and cellular responses to low dose 
exposures to radiation, currently 0.1 Gy (10 rads) or less, with a view 
toward the lower doses. Most scientists in the field would agree that 
not enough is yet known about the biological consequences of low dose 
radiation exposure to be able to completely model human health risk. 
However, it is timely to begin to systematically evaluate different 
approaches for modeling the diversity of available information on the 
biological effects of low dose radiation exposure.
    We define biologically-based risk models as mathematical constructs 
of the key biological 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 stochastic 
and deterministic variables that range from probabilities of inducing 
key molecular events such as cell death, replication or specific gene 
expression, to the description of responses at the tissue level or even 
at the level of the entire organism. Mathematical predictors or 
estimators of radiation risk should ultimately be able to incorporate 
all available epidemiological and experimental information.
    In this solicitation, applications are sought for participation in 
an interactive, biologically-based risk modeling exercise. The first 
activity for the awardees will be to participate in an initial Workshop 
for extensive discussions with experimental researchers and regulatory 
scientists. Awardees will then work to develop a biologically-based 
risk model that includes one or more characteristics important to low 
dose radiobiology.
    Concurrently, awardees will participate in one or more workshops 
for the purpose of developing an artificially defined biological 
archetype. This biological archetype will become the core source of 
biological data, a biological test system for which exact probability 
values are either known or (temporarily) assigned. Quantitative 
information to be defined in the biological archetype will include 
definitions (specific probability values or ranges as a function of 
dose) for such attributes as:
    [sbull] Amount of steady state endogenous DNA damage
    [sbull] Yield of radiation-induced DNA damage (specific lesions)
    [sbull] Efficiency of repair of radiation-induced DNA damage for 
specific lesions (repair capacity, saturation level, error rate)
    [sbull] Radiation-induced gene expression
    [sbull] Radiation-induced genomic instability
    [sbull] Radiation-induced bystander effects (cell-cell 
communication)
    [sbull] Radiation-induced adaptive responses
    [sbull] Genetic susceptibility--for a population of individuals
    [sbull] Current epidemiological information
    [sbull] Etc...
    The biological archetype will eventually be modeled by each funded 
awardee, for the ultimate purpose of comparing the different modeling/
prediction strategies. Please note that the biological archetype will 
be a composite of what is presently established, supplemented where 
needed by best-guess, made-up data.
    The long term goals of this exercise are the following: (1) To 
discover which mechanistic data are usable and which are the most 
critical inputs for development of biologically-based models to predict 
human health risks for low dose exposures (the exercise thus may help 
to define future experimental research needs); and (2) to provide new 
insight into how to extrapolate between different levels of

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biological organization (from molecules to cells to tissues to 
organisms) and from observations in vitro to biological responses in 
vivo.
    Applicants should demonstrate knowledge of and expertise in risk 
modeling. They should discuss general strategies for, or demonstrate 
expertise in the use of, biological mechanistic data in the development 
of risk models. Ideally, the application should exhibit some 
familiarity with relevant radiation biology literature, but prior work 
in this field is not a prerequisite. The Project Description must 
contain the following:
    1. A proposal to develop a biologically-based model taking account 
of one or more phenomena such as adaptive response, bystander effects, 
genetic susceptibility, or genomic instability. A hierarchical scheme 
may be proposed for developing a series of simple to complex 
biologically-based risk models that include successively higher numbers 
of biological parameters.
    2. A discussion of model validation strategies, as well as a 
general discussion of error estimation strategies, should be included. 
(Of great importance will be the determination of how much error can be 
tolerated in each of the critical inputs.)
    3. Briefly, the applicant's ideas on how one would begin to design 
a ``biological archetype'' that could be used to compare different 
models. (What type of biological archetype would be most useful at the 
present time--single cell, cell culture, tissue, mouse, man? In the 
future? Which characteristics of the biological archetype should be 
defined? Which characteristics are known at the present time?)
    Information on the Low Dose Radiation Research Program can be found 
on the Web site: http://lowdose.tricity.wsu.edu.
    Program Funding: It is anticipated that up to $1,500,000 will be 
available for approximately 8 two-year awards, contingent upon the 
availability of funds. Each award will be no more than $200,000, total 
costs per year. If the exercise is judged productive by administrative 
review, some or all awards may be extended an additional year.
    Merit and Relevance 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.

The Application

(Please Note 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 available via 
the World Wide Web: http://www.science.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.
    Adherence to type size and line spacing requirements is necessary 
for several reasons. No applicants should have the advantage of 
providing more text in their applications by using small type. 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). Applications must be written in 
English, with all budgets in U.S. dollars.
    Applicants are asked to use the following ordered format:
    [sbull] Face Page (DOE F 4650.2 (10-91))
    [sbull] Project Abstract Page; single page only, should contain 
title, PI name, and abstract text
    [sbull] Budget page for the one year project period (using DOE F 
4620.1)
    [sbull] Budget Explanation
    [sbull] Project Description; ten (10) pages or less. The 
application should contain the following:
    a. A proposal to develop a biologically-based model taking account 
of one or more phenomena such as adaptive response, bystander effects, 
genetic susceptibility, or genomic instability.
    b. A discussion of model validation strategies, as well as a 
general discussion of error estimation strategies, should be included.
    c. Briefly, the applicant's ideas on how one would design a 
biological archetype that could be used to compare different models 
(approximately one page). .
    [sbull] Literature Cited
    [sbull] Collaborative Arrangements (if applicable)
    [sbull] Facilities and Resources
    [sbull] Biographical Sketches
    [sbull] Current and Pending Support
    [sbull] Letters of Collaboration (if applicable)
    The Office of Science, as part of its regulations, requires at 10 
CFR 605.11(b) that a recipient receiving an award 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.
    DOE requirements for reporting, protection of human and animal 
subjects and related special matters can be found on the World Wide Web 
at: http://www.science.doe.gov/production/grants/Welfare.html.
    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 February 6, 2003.
John Rodney Clark,
Associate Director of Science for Resource Management.
[FR Doc. 03-3939 Filed 2-18-03; 8:45 am]
BILLING CODE 6450-01-P