[Federal Register Volume 67, Number 23 (Monday, February 4, 2002)]
[Notices]
[Pages 5091-5095]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-2593]


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DEPARTMENT OF ENERGY


Office of Science Financial Assistance Program Notice 02-15; Low 
Dose Radiation Research Program--Basic Research

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) and the 
Office of Biological and Physical Research (OBPR), National Aeronautics 
and Space Administration (NASA), hereby announce their interest in 
receiving grant applications for well justified research that supports 
the DOE/OBER Low Dose Radiation Research Program, and that may include 
complementary research of direct interest to the NASA/OBPR Space 
Radiation Health Program that is of sufficient scientific merit to 
qualify for partial NASA support. These Programs use modern molecular 
tools to develop a better scientific basis for understanding exposures 
and risks to humans from low dose and low fluence radiation.
    Research areas of particular programmatic interest include:
     Endogenous oxidative damage versus low dose radiation-
induced damage
     Radio-adaptive responses
     Bystander effects
     Individual genetic susceptibility to low dose radiation 
exposure
    Please review the Supplementary Information section below for 
further discussion of programmatic needs.

DATES: Preapplications (letters of intent) are strongly encouraged, but 
not mandatory. A response to preapplications discussing the potential 
program relevance of a formal application will be communicated within 
one week.
    The deadline for receipt of formal applications is 4:30 P.M., 
E.S.T, April 16, 2002, in order to be accepted for merit review and to 
permit timely consideration for award in Fiscal Year 2002 and Fiscal 
Year 2003.

ADDRESSES: One-page preapplications referencing Program Notice 02-15, 
should be sent by e-mail to [email protected], or by 
facsimile transmission to (301) 903-8521. 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 02-15, 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 02-15. This address 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. Noelle Metting for general 
scientific or technical questions, telephone: (301) 903-8309, e-mail: 
[email protected], Office of Biological and Environmental 
Research, SC-72, U.S. Department of Energy, 19901 Germantown Road, 
Germantown, MD 20874-1290. For specific information on NASA/OBPR 
interests, contact Dr. Walter Schimmerling, telephone: (202) 358-2205, 
e-mail: [email protected], NASA Headquarters, Mail Code UB, 
Washington, DC 20546-0001.

SUPPLEMENTARY INFORMATION: The DOE/OBER Low Dose Radiation Research 
Program is faced with 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. For the present solicitation, DOE/
OBER is chiefly concerned with very low doses of low Linear Energy 
Transfer (LET) radiation (electrons, x- and gamma-rays). The focus of 
research should be

[[Page 5092]]

on doses of low linear energy transfer radiation that are at or near 
current workplace exposure limits. In general, research in this program 
should focus on total radiation doses that are less than or equal to 10 
rads. Some experiments will likely involve selected exposures to higher 
doses of radiation for comparisons with previous experiments or for 
determining the validity of extrapolation methods previously used to 
estimate the effects of low doses of radiation from observations made 
at high doses. Research projects utilizing the ``systems biology'' or 
``discovery science'' approach, including the tools of comparative 
genomics and proteomics, are especially sought. Research projects that 
use experimental protocols or cell microenvironments that will lead to 
an understanding of radiobiological responses in intact human tissue 
are also strongly encouraged. This research program will be a success 
if the science it generates is useful to policy makers, standard 
setters, and the public. Successful applicants will be expected to 
effectively communicate research results whenever possible through 
education and outreach, so that current thinking and the public debate 
reflect sound science.
    The NASA/OBPR Space Radiation Health Program is charged with 
providing input for the determination of health risks to humans 
visiting the space radiation environment. NASA is especially interested 
in human exposure to low fluences of high-energy particulate ionizing 
radiation (protons and heavy ions). Where possible, projects that 
address the interests of both DOE/OBER and NASA/OBPR are particularly 
encouraged. Applications whose principal focus is on low LET radiation 
are encouraged to include complementary research with high-energy 
particulate ionizing radiation that leverages progress, resources, and 
technology used for the low LET radiation research (see Specifics for 
NASA below). Investigators with currently funded low dose projects may 
also apply for supplementary funding to address closely related 
research of interest to NASA.
    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. In the 
present context, the research considered to be most useful will focus 
on biological responses that:
     Are known to be induced at low doses of radiation,
     Have the potential to directly impact (i.e., increase or 
decrease) 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, and
     Could potentially lead to the development of biological 
predictors (biomarkers) of individual risk.
    Alternatively, a biological response of interest could meet all of 
the above criteria only at high doses but may actually be absent (as 
opposed to 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, and 
delimiting the unique doses where these mechanisms shift is important.
    Endogenous oxidative damage in relation to low dose radiation 
induced damage--A key goal of this research program will remain the 
elucidation of similarities and differences between endogenous 
oxidative damage and damage induced by low levels of ionizing 
radiation, as well as understanding the health risks from both. This 
information will underpin our interpretation of the biological effects 
of exposure to low doses of ionizing radiation. Although qualitative 
descriptions of differences and/or similarities between the types of 
damage induced under both conditions will be useful in the design and 
interpretation of experiments in other parts of the program, there is a 
need for quantification of the levels of damage induced by normal 
oxidative processes and incremental increases due to low dose 
irradiation.
    Living organisms are subject to a daily plethora of environmental 
insults. Carcinogenesis in an individual occurs as a function of all 
the forces and phenomena that go into the production of that 
individual's phenotype. These include (but are not limited to) 
individual genotype, as well as current and historical aspects of diet, 
physical exercise, and exposures to chemicals and radiation. To 
understand all factors responsible for individual responses to 
radiation, we are also soliciting research on key factors that 
influence the extent of metabolic, endogenously produced oxidative 
damage and, concomitantly, affect susceptibility to low doses of 
radiation.
    Radio-Adaptive Response--The ability of a low dose of radiation to 
induce cellular changes that alter the level of subsequent radiation-
induced or spontaneous damage. If low doses of radiation regularly and 
predictably induce a protective response in cells exposed to subsequent 
low doses of radiation or to spontaneous damage, this could have a 
substantial impact on estimates of adverse health risk from low dose 
radiation. The generality and the extent of the process of the 
induction itself need to be quantified, and the responsible genes and 
proteins discovered. By ``generality'' is meant quantification as a 
function of cell tissue type and species type; by ``extent'' is meant 
quantification as a function of priming dose, dose rate, and time 
constant of action.
    Bystander effects--Biological responses observed in cells that are 
not directly traversed by radiation but are neighbors of an irradiated 
cell. Bystanders in cell monolayers have been shown to respond with 
gene induction and/or production of clastogenic changes. It is 
important for the DOE/OBER Low Dose program to determine if bystander 
effects can be induced by exposure to low LET radiation delivered at 
low total doses. A detrimental bystander effect, in essence, 
``amplifies'' the biological effects (and the effective radiation dose) 
of a low dose exposure by effectively increasing the number of cells 
that experience adverse effects to a number greater than the number of 
cells directly exposed to radiation. Conversely, bystander cells may in 
some cases exert a protective effect on the irradiated cell or cells, 
although very few studies of this type of effect have been tried. More 
importantly, entirely different types or levels of bystander effects 
may be occurring in three-dimensional tissues and intact organisms. 
Hence, there is considerable interest in extending studies to tissues, 
or at least toward more complex tissue-like models, and priority 
consideration will be given to these projects. Research is sought to 
characterize and determine mechanisms of low LET radiation induced 
bystander effect, and to quantify its induction and extent as a 
function of dose. New research projects studying bystander effects in 
isolated cells or cell monolayers will be considered only in 
exceptionally well-justified or novel approach cases.
    Individual genetic susceptibility to low dose radiation--The Low 
Dose Radiation Research Program is interested in determining if genetic 
differences exist that result in sensitive individuals or sub-
populations that are at increased risk for radiation-induced cancer. 
For example, research could focus on genes involved in the recognition, 
repair, and processing of damage induced by ionizing radiation, or on 
genes involved in maintaining the

[[Page 5093]]

normal degree of irreversibility of cell differentiation for a 
particular tissue. Of critical interest would be the identification of 
these genes, determining frequencies of their polymorphisms in the 
population, and determining the biological significance of these 
polymorphisms with respect to cancer and radiation sensitivity. 
Ingenious, high throughput approaches, that evaluate many endpoints or 
individuals experimentally using pooling schemes, are of particular 
interest. We are also interested in mouse models that speed the 
discovery or characterization of putative human susceptibility genes. 
New studies focused only on a single or a few genes will not be funded 
unless substantial evidence is provided that those genes play a 
significant role in individual susceptibility to radiation. A long-term 
goal is to identify any genetic polymorphisms that significantly impact 
individual and population-level sensitivity to radiation, and 
characterize their mechanism of action.
    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. The program is currently funding a number 
of projects to develop micro-irradiation devices capable of delivering 
low doses of low LET radiation to individual cells or to specific parts 
of individual cells. For links to currently funded ``microbeam'' 
projects see: http://lowdose.org/99meeting/abstracts/tool.html--
projects 26, 28, 29 and also: http://lowdose.org/99meeting/abstracts/response.html--project 3. Investigators are encouraged to use these or 
similar irradiators, as appropriate, in the design and conduct of their 
research. Funds are available to assist in the collaborative use of 
these or comparable tools.
    Other resource considerations--Research in the areas discussed 
above will strongly complement ongoing initiatives at the National 
Institutes of Health (NIH). DOE/OBER staff is working with staff at the 
NIH to ensure that research in the Low Dose Radiation Research Program 
is not duplicative of research funded by NIH programs.
    A collaborative effort of five major centers, termed the 
International SNP Map Working Group, along with over 50 other 
contributing laboratories, are creating the largest publicly available 
catalog of single base-pair differences between two copies of the same 
gene (single nucleotide polymorphisms, or SNPs). The current catalog 
contains 1.4 million SNPs, each with their exact location mapped within 
the human genome. SNPs are the most common polymorphisms in the human 
genome, and some contribute to the traits that make us unique 
individuals. The catalog (http://www.ncbi.nlm.nih.gov/SNP/index.html) 
will be a boon for mapping complex traits such as cancer susceptibility 
and susceptibility to low dose radiation.
    Inbred mouse strains and other model organisms with well-
characterized differences in susceptibility to radiation-induced cancer 
are also important tools for identifying significant polymorphisms. 
Direct assessment of the biological significance of candidate 
``susceptibility genes'' can also be undertaken using animal models 
such as knockout and knock-in mice, mice with specific genes removed or 
added.

Specifics for the Space Radiation Health Program--NASA

    The primary area of emphasis of the NASA/OBPR Space Radiation 
Health Program is the development of mechanistic insights into 
biological effects of space radiation that account for radiation risks. 
Applications are required to be hypothesis-driven and are expected to 
obtain their data in ground-based experimental radiobiology studies 
with protons and high-energy heavy ion beams in the energy range 
corresponding to space radiation. This is mainly a ground-based program 
using accelerator facilities to simulate space radiation. In addition 
to the research topics already described above this includes research 
on non-phenomenological predictors of late cell and tissue effects and 
the control and modification of radiation effect mechanisms
    A short description of the current Space Radiation Health Strategic 
Program may be found at: http://spaceresearch.nasa.gov/common/docs/1998_radiation_strat_plan.pdf. Activities of OBPR, including research 
opportunities, descriptions of previous tasks, and other relevant 
information can be found at: http://SpaceResearch.nasa.gov/. A 
description of the ground-based facilities and experimental program at 
Brookhaven National Laboratory can be found at: http://www.bnl.gov/medical/NASA/NASA-home%20frame.htm. The proton therapy facilities at 
Loma Linda University Medical Center are described at: http://www.llu.edu/proton/patient/nasa1.html. Finally, a description of the 
NASA Specialized Center of Research and Training at the Lawrence 
Berkeley National Laboratory may be found at: http://www.lbl.gov/lifesciences/NSCORT.
    Scientists working in rapidly developing areas of biological 
sciences not necessarily associated with the study of radiation are 
particularly encouraged to consider the contributions that their field 
of study can make to Radiation Health. Applications are required to 
provide evidence for expertise in radiation, either by reference to the 
Principal Investigator's work or by inclusion of active collaborators 
expert in radiation research. Hypotheses should be substantiated by 
presentation of preliminary data wherever feasible, or by adequate 
references to the published literature. Experimental applications 
should include a clear discussion of the relevant aspects of the 
required radiation dosimetry and an estimate of the statistical power 
of the expected results.
    Research applications to which NASA will assign high priority:
    a. Studies that increase the confidence in the accuracy of 
extrapolating the probability of radiation-induced genetic alterations 
or carcinogenesis from rodents to humans.
    b. Determination of carcinogenic risks following irradiation by 
protons and HZE particles.
    c. Determination if exposure to heavy ions at the level that would 
occur in deep space poses a risk to the integrity and function of the 
central nervous system.
    d. Studies likely to result in the development of biological 
countermeasures in humans that could lead to prevention or intervention 
(including genetic or pharmacological agents) against effects of 
radiation damage in space.
    Research that can lead to future space flight investigations will 
be welcome, and should take into account the impact of gender, age, 
nutrition, stress, genetic predisposition, or sensitivity to other 
factors of importance in managing space radiation risks.
    NASA envisions that the selected applications will be structured 
and operated in a manner that supports the country's educational 
initiatives and goals (including historically black colleges and 
universities and other minority universities), and in particular the 
need to promote scientific and technical education at all levels. NASA 
envisions that the selected applications will support the goals for 
public awareness and outreach to the general public. The selected 
investigators are invited to participate in NASA-funded educational 
programs.

[[Page 5094]]

    The applications represent an opportunity to enhance and broaden 
the public's understanding and appreciation of radiation effects, as 
specified in the DOE Low Dose Program emphasis on communication of 
research results and the OBPR Policy for Education and Public Outreach. 
Therefore, all investigators are strongly encouraged to promote general 
scientific literacy and public understanding of radiation induced 
health risk research through formal and/or informal education 
opportunities. If appropriate, applications should include a clear and 
concise description of the education and outreach activities proposed. 
Examples include such items as involvement of students in the research 
activities, technology transfer plans, public information programs that 
will inform the general public of the benefits being gained from the 
research, and/or plans for incorporation of scientific results obtained 
into educational curricula consistent with educational standards.
    Where appropriate, the supported institution will be required to 
produce, in collaboration with NASA, a plan for communicating to the 
public the value and importance of their work.
    The particles of interest to the Space Radiation Health Program are 
protons with energies between 20 and 1000 MeV, and nuclei of He, C, N, 
O, Ne, Si, Ar, Ca, Mn, and Fe, with energies between 50 and 3000 MeV/
nucleon. Fluencies of interest are of the order of 1-2 particles per 
cell; studies with higher fluencies will need to be justified by 
compelling arguments, including an explanation of how the results can 
be applied in the low fluency regime. NASA has developed facilities for 
use of protons at Loma Linda University Medical School and high-energy 
heavy ion beams at the Brookhaven National Laboratory Alternating 
Gradient Synchrotron (AGS). A dedicated irradiation facility, using the 
Booster Synchrotron at Brookhaven, is under construction and is 
expected to be operational in 2003. Applications should not budget for 
the use of beams at these facilities, which is paid by NASA. NASA will 
cooperate with DOE to expand the range of technical resources available 
for experimentation and analysis of experimental results at Brookhaven.

Program Funding

    It is anticipated that up to $2.5 million will be available from 
DOE/OBER for new grant awards during Fiscal Year 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. 
Applications whose principal focus is on low LET radiation can include 
complementary research on high-energy particulate ionizing radiation 
that leverages progress, resources and technology used for the low LET 
radiation research. Up to $0.5M will be available from NASA in the 
first year, with higher amounts projected for successive years, also 
contingent upon the availability of funds. Funds will be available from 
DOE to assist in the collaborative use of certain microbeam 
irradiators. NASA provides beam time at the Brookhaven AGS and the Loma 
Linda proton accelerator; investigators will not be required to pay for 
the beam time. It is expected that most awards will be from 1 to 3 
years and will range from $200,000 to $500,000 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.

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. 
Applications found to be scientifically meritorious and 
programmatically relevant will be selected in consultation with DOE and 
NASA selecting officials depending upon availability of funds in each 
agency's budget. In the course of the selection process, projects will 
be identified as addressing DOE requirements, NASA requirements, or 
both. The selected projects will be required to acknowledge support by 
one or both agencies, as appropriate, in all public communications of 
the research results.

The Application

(Please Note Critical New 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/guide.html. In particular, please note the instructions on 
Collaboration available via the World Wide Web: http://www.science.doe.gov/production/grants/Colab.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 expected to use the following ordered format, in 
addition to following instructions in the Application Guide for the 
Office of Science Financial Assistance Program.

Face Page (DOE F 4650.2 (10-91))

     Project Abstract Page--Single page only, should contain:
     Title
     PI name
     Abstract text should concisely describe the overall 
project goal in one sentence, and limit background/significance of 
project to one sentence.

[[Page 5095]]

Short descriptions of each individual aim should focus on what will 
actually be done
     Relevance Statement--Single page only, should identify DOE 
or NASA requirements that each specific aim is intended to address
     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 (again, see information at: 
http://www.science.doe.gov/production/grants/Colab.html)
     Project Description--(The Project Description must be 20 
pages or less, exclusive of attachments. Applications with Project 
Descriptions longer than 20 pages will be returned to applicants and 
will not be reviewed for scientific merit.) The Project Description 
should contain the following five parts:
     Goals
     Background (concisely-stated, relevant)
     Experimental Approach
     Preliminary Studies (and Progress, if applicable)
     Statistical Design and Methodologies
     Literature Cited
     Collaborative Arrangements (if applicable)
     Biographical Sketches (limit 2 pages per senior 
investigator, consistent with NIH guidelines)
     Facilities and Resources description
     Current and Pending Support for each senior investigator
     Letters of Intent from collaborators (if applicable)
    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.
    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 January 23, 2002.
John Rodney Clark,
Associate Director of Science for Resource Management.
[FR Doc. 02-2593 Filed 2-1-02; 8:45 am]
BILLING CODE 6450-02-P