[Federal Register Volume 67, Number 212 (Friday, November 1, 2002)]
[Pages 66619-66623]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-27800]



Office of Science Financial Assistance Program Notice 03-07; Low 
Dose Radiation Research Program--Basic Research

AGENCY: Department of Energy.

ACTION: Notice inviting grant applications.


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 new research to develop a better 
scientific basis for understanding exposures and risks to humans from 
low dose and low fluence radiation. Topics of high priority include 
endogenous oxidative damage versus low dose radiation-induced damage, 
radio-adaptive responses, bystander effects, and individual genetic 
susceptibility to low dose radiation exposure. Research should employ 
genome-wide or proteome-wide high-throughput screening methods whenever 
possible, and priority will also be given to the use of three-
dimensional biological models. Research should support the DOE/OBER Low 
Dose Radiation Research Program, and may include complementary research 
of direct interest to the NASA/OBPR Space Radiation Health Program of 
sufficient scientific merit to qualify for partial NASA support. Please 
review the SUPPLEMENTARY INFORMATION section below for further 
discussion of programmatic needs.
    The Office of Biological and Environmental Research of the Office 
of Science, U.S. Department of Energy also announces its interest in 
receiving smaller applications for grants to support collaborative work 
between two or more laboratories, one or more of which should be funded 
to do low dose-related research. Please review the SUPPLEMENTARY 
INFORMATION section on Glue Grants, below, for further details.
    In addition, we anticipate a separate request for modeling projects 
in the near future.

DATES: Preapplications (letters of intent), including information on 
collaborators, areas of research, and a one-page summary of the 
proposed research, should be submitted by December 6, 2002.
    Formal applications submitted in response to this notice must be 
received by 4:30 p.m., E.S.T., Thursday, February 27, 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 03-07, should be 
sent to Ms. Joanne Corcoran by E-mail: [email protected], 
with a copy to Dr. Noelle Metting at: [email protected].

[[Page 66620]]

    Formal applications in response to this solicitation are to be 
electronically submitted by an authorized institutional business 
official through DOE's Industry Interactive Procurement System (IIPS) 
at: http://e-center.doe.gov/. 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: 
center.doe.gov">[email protected]center.doe.gov 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 an 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 instructions on how to submit printed 

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. 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.


(1) Specifics for the Low Dose Radiation Research Program (DOE)

    The DOE/OBER 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. 
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 on doses of low LET 
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. 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 through 
publication in peer-reviewed journals. They will also be encouraged to 
communicate with the wider community of concerned persons, so that 
current thinking and the public debate is better able to reflect sound 
    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.
    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 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 
evidence is accumulating that the mechanisms of action are different 
after high versus low doses of radiation, such studies would help 
define these mechanisms. Defining the doses where these mechanisms 
shift is of critical importance.
    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 
    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 
    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 extent of the induction process need to 
be quantified, and the responsible genes and proteins discovered. By 
``generality'' is meant its applicability to different cell tissue 
types and species; by ``extent'' is meant quantification over a range 
of priming doses, dose rates, and time constants of action.
    Bystander effects--Biological responses observed in cells that are 
not directly traversed by radiation but are neighbors of an irradiated 
cell. Research is sought to characterize and determine mechanisms of 
low LET radiation

[[Page 66621]]

induced bystander effect, and to quantify its induction and extent as a 
function of dose. Bystanders in cell monolayers have already been shown 
to respond with gene induction and/or production of clastogenic 
changes. 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 exert a 
protective effect on the irradiated cell or cells, although very few 
studies to detect this effect have been tried. More importantly, 
entirely different types or levels of bystander effects may be 
occurring in three-dimensional tissues, organs, and intact organisms. 
Hence, only those applications that address effects in tissues, or in 
tissue-like models, will be considered for funding. New research 
projects studying bystander effects in isolated cells or cell 
monolayers will not be considered.
    Because applications to study bystander effects are limited to 
three-dimensional biological models, investigators are also encouraged 
to propose novel bioimaging protocols for the purpose of in situ 
    The DOE Low Dose Program is currently funding several 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. Investigators are encouraged to use these 
irradiators, as appropriate, through collaborative means, and funds are 
available to assist in the collaborative use of these or comparable 
tools. Information on the microbeam irradiators can be found at: http://lowdose.tricity.wsu.edu.
    Individual genetic susceptibility to low dose radiation. The Low 
Dose Radiation Research Program is interested in determining if genetic 
differences exist that result in increased risk for radiation-induced 
cancer in sensitive individuals or sub-populations. It may prove to be 
of value to address the three previously discussed research areas of 
interest (endogenous damage, radio-adaptive responses, and bystander 
effects) from the standpoint of genetic susceptibility. A major goal 
for this solicitation is to support additional work that seeks to 
identify patterns of genetic polymorphisms significantly impacting 
radiation sensitivity or resistance and characterizes their mechanism 
of action. Research should employ genome-wide or proteome-wide high-
throughput screening methods that have a chance of ultimately detecting 
complex, multi-gene patterns indicative of or related to 
susceptibility. New studies focused only on a single or even a few 
hundred genes will not be funded.
    A new resource that is now available to all Low Dose Program 
investigators, but might be of particular interest to those proposing 
research in the area of genetic susceptibility, is a tissue repository 
containing cells from patients who developed second cancers following 
total body irradiation and hematopoietic stem cell transplantation 
(HSCT). Presently there are EBV-transformed cell lines from 25 
individuals exposed to radiation who subsequently developed a skin 
tumor, and an equal number from exposed individuals that have not yet 
developed a second cancer. A much larger tissue resource will be 
available in the future. Please contact directly Dr. Jeffrey L. 
Schwartz, Associate Professor of Radiation Oncology, University of 
Washington, (206) 598-4091, E-mail: [email protected], for 
collaborative opportunities.
    General information resources. Information on the Low Dose 
Radiation Research Program can be found on the web site: http://lowdose.tricity.wsu.edu. Prospective proposers are also encouraged to 
visit the National Center for Biotechnology Information (NCBI) website: 
http://www.ncbi.nlm.nih.gov/, for information on techniques and 
resources, and especially its Science Primer web site: http://www.ncbi.nlm.nih.gov/About/primer/snps.html, for an introduction to 
single nucleotide polymorphisms (SNPs).

(2) Specifics for the Space Radiation Health Program (NASA)

    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). 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. Investigators with currently funded low dose projects may 
also apply for supplementary funding to address closely related 
research of interest to 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%20Page.htm. The proton therapy facilities at Loma 
Linda University Medical Center are described at: http://www.llu.edu/llu/ci/nasa/. 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

[[Page 66622]]

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 
    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. Fluences of interest are of the order of 1-2 particles per 
cell; studies with higher fluences will need to be justified by 
compelling arguments, including an explanation of how the results can 
be applied in the low fluence 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.

(3) Specifics for Glue Grants

    The Low Dose Radiation Research Program also announces its interest 
in receiving applications for the purpose of supporting collaborative 
work between two or more laboratories, one or more of which should be 
funded to do low dose-related research. These small grants are 
primarily designed to support post-doctoral or graduate-student 
research that will enable laboratories with complementary expertise to 
develop and apply innovative new approaches to low dose research. 
Comparative studies between laboratories already using similar 
experimental approaches are also encouraged. At least one of the 
applicants must hold a grant focusing on low dose issues. All 
applicants must have at least 1 year (and preferably 2 years) of 
support remaining on their core grants at the time of award. 
Collaborative glue grants can be set up between laboratories funded by 
such diverse agencies as DOE, NIH/NCI, NASA, DOD, EPA, the European 
Union, Canada, France, and Japan, but in any case preference will be 
given to proposed research that is of interest to the DOE Low Dose 
Radiation Research Program. The proposed collaborative research should 
add a new dimension or approach to at least one of the studies it is 
linking. Applications for these small grants must follow the 
instructions in IIPS for electronic submission. Please note: the 
Project Description should not exceed five pages.

Program Funding

    It is anticipated that up to $4 million will be available from DOE/
OBER for new basic research awards during FY 2003, 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. Up to ten 
3-year Glue Grants may be awarded, each averaging $60,000 total costs 
per year. Up to $0.5M will be available from NASA for joint funding of 
new research in Fiscal Year 2003, 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 
$100,000 to $500,000 per year (total costs).


    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. Additional information on collaboration is available in the 
Application Guide for the Office of Science Financial Assistance 
Program that is available via the Internet at: http://www.sc.doe.gov/production/grants/Colab.html.

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 
    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 
    4. Reasonableness and Appropriateness of the Proposed Budget.
    The evaluation will include program policy factors such as the 
relevance of

[[Page 66623]]

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 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. DOE is under no obligation to pay for any costs associated 
with the preparation or submission of applications if an award is not 
    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:

--PI name,
--Abstract text should concisely describe the overall project goal in 
one sentence, and limit background/significance of project to one 
sentence. Short descriptions of each individual aim should focus on 
what will actually be done

    [sbull] Relevance Statement; single page only, should identify DOE- 
or NASA-relevant research that each specific aim is intended to 
    [sbull] Budget pages for each year and a summary budget page for 
the entire project period (using DOE F 4620.1).
    [sbull] Budget Explanation.
    [sbull] Budget pages and budget explanation for each collaborative 
subproject, if any.
    [sbull] Project Description, 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. (Project Descriptions for Glue Grants should not 
exceed 5 pages.) The Project Description should contain the following 
five parts:

--Background (concisely-stated, relevant),
--Experimental Approach,
--Preliminary Studies (or Progress, if this is a renewal application),
--Statistical Design and Methodologies

    [sbull] Literature Cited.
    [sbull] Collaborative Arrangements (if applicable).
    [sbull] Biographical Sketches (limit 2 pages per senior 
investigator, consistent with NIH guidelines).
    [sbull] Facilities and Resources description.
    [sbull] Current and Pending Support for each senior investigator.
    [sbull] 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 

    Issued in Washington, DC on October 28, 2002.
John Rodney Clark,
Associate Director of Science for Resource Management.
[FR Doc. 02-27800 Filed 10-31-02; 8:45 am]