[Federal Register Volume 67, Number 212 (Friday, November 1, 2002)]
[Notices]
[Pages 66619-66623]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-27800]
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DEPARTMENT OF ENERGY
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.
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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 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">HelpDesk@e-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
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. 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:
(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
science.
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
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 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
quantification.
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
programs.
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).
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. 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
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
[[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
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,
--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
address.
[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:
--Goals,
--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
605.
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]
BILLING CODE 6450-03-P