DEPARTMENT OF ENERGY For more information about the Office of Science, go to Office of Science |
To DOE National Laboratories LAB 01-18
Low Dose Radiation Research Program
The Office of Biological and Environmental Research (OBER) of the Office of
Science (SC), U.S. Department of Energy (DOE), hereby announces their interest in receiving
proposals for research that supports the DOE/OBER Low Dose Radiation Research
Program.
Research is sought by the DOE/OBER Low Dose Radiation Research Program for studies
involving low LET radiation, in the following areas:
SUPPLEMENTARY INFORMATION:
Description of Research Program Areas
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 LET radiation (x and gamma rays). There are three
biological responses of specific interest for this solicitation that are most likely to meet the
criteria outlined below. These include bystander effects, induction of genomic instability, and
adaptive responses. Proposals proposing the use of additional biological responses will be
considered only if the biological responses proposed for investigation can be reasonably
demonstrated to meet the criteria outlined below. All proposals focused on the
characterization of specific biological responses, e.g., bystander effects, etc., should identify how
the response of interest meets these criteria. There is also considerable interest in determining
whether these biological responses can be extended from studies in isolated cells to tissues or to
more complex tissue-like systems. These responses are discussed here:
Bystander effects - The biological response observed in cells that are not directly traversed by
radiation but are neighbors of an irradiated cell. Bystanders have been shown to respond with
gene induction and/or production of potential genetic and carcinogenic changes. It is important
for the DOE/OBER Low Dose program to determine if these so-called bystander effects can be
induced by exposure to low LET (linear energy transfer) radiation delivered at low total doses or
dose-rates. If such an effect is demonstrated and quantifiable, it could, potentially, increase
estimates of risk from low dose radiation. This 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. Research is sought to:
Endogenous versus low dose radiation induced damage. A key element of this research
program will continue to be the development of an understanding of the similarities and
differences between endogenous oxidative damage and damage induced by low levels of
ionizing radiation, as well as an understanding of the health risks from both. This information
will underpin our interpretation of the biological effects of exposure to low doses of ionizing
radiation. Although always needed, this information was not previously attainable because
critical resources and technologies were not available. Today, technologies and resources such as
those developed as part of the human genome program, e.g., coupled capillary electrophoresis
and mass spectrometry systems and DNA sequence information, have the potential to detect and
characterize small differences in damage induced by normal oxidative processes and low doses
of radiation. A significant investment in technology development will be required to expand
current capabilities for identifying and quantifying small amounts of oxidative or radiation
induced damage. Radically new technologies are likely not needed but current technologies will
need to be modified. Methodologies having high sensitivity as well as high signal-to-noise ratio
will be critical in this effort.
A significant research effort will be required to characterize and quantify normal oxidative
damage in cells and the incremental increases induced by low doses of ionizing radiation.
Preference will be given to the formation of partnerships between laboratories involved in
characterization and quantification of radiation and oxidative damage and groups with expertise
in or developing new technology to facilitate progress in both areas simultaneously. 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, levels of damage induced by normal oxidative processes and incremental
increases due to low dose radiation should be quantified.
Genetic factors that affect individual susceptibility to low dose radiation. The Low Dose
Radiation Research Program is interested in determining if genetic differences exist making
some individuals more sensitive to radiation-induced damage since these differences could result
in sensitive individuals or sub-populations that are at increased risk for radiation-induced cancer.
Research should focus on:
The National Human Genome Research Institute (NHGRI) is funding research to identify
common variants in the coding regions of the majority of human genes identified during the next
five years with the goal of developing a catalog of all common variants. The NHGRI is also
working to create a map of at least 100,000 single nucleotide polymorphisms (SNPs), the most
common polymorphisms in the human genome representing single base-pair differences between
two copies of the same gene. These SNPs will be a boon for mapping complex traits such as
cancer, cancer susceptibility, and susceptibility to low dose radiation.
The National Institute of Environmental Health Science (NIEHS) is funding research as part of
its Environmental Genome Project to understand the impact and interaction of environmental
exposures on human disease. The NIEHS project includes efforts to understand genetic
susceptibility to environmental agents that will allow more precise identification of the
environmental agents that cause disease and the true risks of exposures. The principal focus of
NIEHS research will be on chemicals, so the focus on radiation in the Low Dose Radiation
Research Program is highly complementary. Initially, the Environmental Genome Project will
focus on categories of genes including: xenobiotic metabolism and detoxification genes,
hormone metabolic genes, receptor genes, DNA repair genes, cell cycle genes, cell death control
genes, genes mediating immune and inflammatory responses, genes mediating nutritional
factors, genes involved in oxidative processes and genes for signal transduction systems.
Identification of potential susceptibility genes and polymorphisms in those genes is only the first
(and perhaps the easiest) step in the program to characterize and understand genetic
susceptibility. Determining the biological significance of these genetic polymorphisms with
respect to cancer and radiation sensitivity is the ultimate goal and the more difficult task. The
international human genome project, structural biology research, and the NHGRI and NIEHS
efforts described above play important roles determining which polymorphisms are most likely
to influence gene function. Population genetics and computational biology approaches will be
required to estimate the potential impact on estimates of population and individual risk. Genetic
epidemiology approaches will also be needed to relate specific polymorphisms and combinations
of polymorphisms with cancer risk. 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.
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.
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. It is our belief that the most useful
research will focus on biological responses that:
The focus of research in the Low Dose Radiation Research Program should be on doses of low
linear energy transfer (LET) radiation that are at or below 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 that principally focuses on radiation doses greater than 10 rads,
high LET radiation or non-ionizing radiation will not be considered without substantial
justification.
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
http://lowdose.org/99meeting/abstracts/response.html – project 3. Investigators are strongly
encouraged to use these or similar tools, as appropriate, in the design and conduct of their
research. Funds are available to assist in the collaborative use of these or comparable tools or, in
some cases, to provide low-cost micro-irradiation devices to individual investigators.
DATES: Potential proposers should submit a one page preproposal referencing Program
Announcement LAB 01-18 by 4:30 P.M. E.S.T., February 15, 2001. Receipt of preproposals sent by email
will be acknowledged by a return message. An E-mail response to preproposals discussing the
potential program relevance of a formal proposal generally will be communicated by
February 22, 2001.
The deadline for receipt of formal proposals is 4:30 P.M., E.D.T., May 15, 2001, in order to
be accepted for merit review and to permit timely consideration for award in FY 2001 and FY
2002.
ADDRESS: Preproposals referencing Program Announcement LAB 01-18, should be sent by E-mail to
joanne.corcoran@science.doe.gov.
Preproposals 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 proposals, referencing Program Announcement LAB 01-18, should be sent to: U.S. Department of
Energy, Office of Science, Grants and Contracts Division, SC-64, 19901 Germantown Road,
Germantown, MD 20874-1290, ATTN: Program Notice 01-18. This address must be used when
submitting proposals by U.S. Postal Service Express, commercial mail delivery service, or
when hand carried by the proposer.
FOR FURTHER INFORMATION CONTACT: For general information, contact Dr. David
Thomassen, telephone: (301) 903-9817, E-mail:
david.thomassen@science.doe.gov,
Office of
Biological and Environmental Research, SC-72, U.S. Department of Energy, 19901 Germantown
Road, Germantown, MD 20874-1290.
Program Funding
It is anticipated that up to $4.0 million will be available from DOE/OBER for new awards
during FY 2001 and FY 2002, contingent upon the availability of funds. Multiple year funding
of awards is expected, and is also contingent upon the availability of appropriated funds,
progress of the research, and continuing program need. It is expected that most awards will be
from 1 to 5 years and will range from $200,000 to $400,000 per year (total costs). Proposals
requesting more than 3 years of funding will need to clearly justify the benefits of the additional
years of research to the goals of the low dose radiation research program. Please note that funds
are available from DOE to assist in the collaborative use of certain microbeam irradiators. DOE is
under no obligation to pay for any costs associated with the preparation or submission of
proposals if an award is not made.
Collaboration
Proposers are encouraged to collaborate with researchers in other institutions, where
appropriate.
Preproposal
A preproposal should be submitted. The Preproposal should contain a title, list of
investigators, address, telephone, fax and E-mail address of the Principal Investigator, and no
more than a one page summary of the proposed research, including project objectives and
methods of accomplishment. Responses to the preproposals, encouraging or discouraging
formal proposals, will generally be communicated within 7 days of receipt. Notification of a
successful preproposal is not an indication that an award will be made in response to the
formal proposal.
Proposals
DOE is under no obligation to pay for any costs associated with the preparation or submission of proposals if an award is not made. The Project Description must be 25 pages or less, exclusive of attachments. Proposals with Project Descriptions longer than 25 pages will be returned to proposer and will not be reviewed. The proposal must contain an abstract or project summary, letters of intent from collaborators, and short curriculum vitaes consistent with NIH guidelines. Adherence to type size and line spacing requirements is necessary for several reasons. No proposers should have the advantage, or by using small type, of providing more text in their proposals. Small type may also make it difficult for reviewers to read the proposal. Proposals 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 proposer 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). Proposers are expected to use the following ordered format to prepare proposals in addition to following instructions in the GUIDE FOR PREPARATION OF SCIENTIFIC/TECHNICAL PROPOSALS TO BE SUBMITTED BY NATIONAL LABORATORIES below. Proposals must be written in English, with all budgets in U.S. dollars.
Any recipient of an award from the Office of Science, performing research involving recombinant DNA molecules and/or organisms and viruses containing recombinant DNA molecules shall comply with the National Institutes of Health "Guidelines for Research Involving Recombinant DNA Molecules," which is available via the World Wide Web at: http://www.niehs.nih.gov/odhsb/biosafe/nih/rdna-apr98.pdf, (59 FR 34496, July 5, 1994), or such later revision of those guidelines as may be published in the Federal Register.
The instructions and format described below should be followed. Reference Program Announcement LAB 01-18 on all submissions and inquiries about this program.
GUIDE FOR PREPARATION OF SCIENTIFIC/TECHNICAL PROPOSALS TO BE SUBMITTED BY NATIONAL LABORATORIES Proposals from National Laboratories submitted to the Office of Science (SC) as a result of this program announcement will follow the Department of Energy Field Work Proposal process with additional information requested to allow for scientific/technical merit review. The following guidelines for content and format are intended to facilitate an understanding of the requirements necessary for SC to conduct a merit review of a proposal. Please follow the guidelines carefully, as deviations could be cause for declination of a proposal without merit review. 1. Evaluation Criteria Proposals will be subjected to formal merit review (peer review) and will be evaluated against the following criteria which are listed in descending order of importance:
Appropriateness of the proposed method or approach Competency of the personnel and adequacy of the proposed resources Reasonableness and appropriateness of the proposed budget 2. Summary of Proposal Contents
Proposal Cover Page Table of Contents Abstract Narrative Literature Cited Budget and Budget Explanation Other support of investigators Biographical Sketches Description of facilities and resources Appendix An original and seven copies of the formal proposal/FWP must be submitted. 3. Detailed Contents of the Proposal Proposals must be readily legible, when photocopied, and must conform to the following three requirements: the height of the letters must be no smaller than 10 point with at least 2 points of spacing between lines (leading); the type density must average no more than 17 characters per inch; the margins must be at least one-half inch on all sides. Figures, charts, tables, figure legends, etc., may include type smaller than these requirements so long as they are still fully legible.
3.1 Field Work Proposal Format (Reference DOE Order 5700.7C) The Field Work Proposal (FWP) is to be prepared and submitted consistent with policies of the investigator's laboratory and the local DOE Operations Office. Additional information is also requested to allow for scientific/technical merit review. Laboratories may submit proposals directly to the SC Program office listed above. A copy should also be provided to the appropriate DOE operations office. 3.2 Proposal Cover Page The following proposal cover page information may be placed on plain paper. No form is required.
SC Program announcement title Name of laboratory Name of principal investigator (PI) Position title of PI Mailing address of PI Telephone of PI Fax number of PI Electronic mail address of PI Name of official signing for laboratory* Title of official Fax number of official Telephone of official Electronic mail address of official Requested funding for each year; total request Use of human subjects in proposed project:
Signature of official, date of signature* *The signature certifies that personnel and facilities are available as stated in the proposal, if the project is funded. Provide the initial page number for each of the sections of the proposal. Number pages consecutively at the bottom of each page throughout the proposal. Start each major section at the top of a new page. Do not use unnumbered pages and do not use suffices, such as 5a, 5b. 3.4 Abstract Provide an abstract of no more than 250 words. Give the broad, long-term objectives and what the specific research proposed is intended to accomplish. State the hypotheses to be tested. Indicate how the proposed research addresses the SC scientific/technical area specifically described in this announcement. 3.5 Narrative The narrative comprises the research plan for the project and is limited to 25 pages. It should contain the following subsections: Background and Significance: Briefly sketch the background leading to the present proposal, critically evaluate existing knowledge, and specifically identify the gaps which the project is intended to fill. State concisely the importance of the research described in the proposal. Explain the relevance of the project to the research needs identified by the Office of Science. Include references to relevant published literature, both to work of the investigators and to work done by other researchers. Preliminary Studies: Use this section to provide an account of any preliminary studies that may be pertinent to the proposal. Include any other information that will help to establish the experience and competence of the investigators to pursue the proposed project. References to appropriate publications and manuscripts submitted or accepted for publication may be included. Research Design and Methods: Describe the research design and the procedures to be used to accomplish the specific aims of the project. Describe new techniques and methodologies and explain the advantages over existing techniques and methodologies. As part of this section, provide a tentative sequence or timetable for the project. Subcontract or Consortium Arrangements: If any portion of the project described under "Research Design and Methods" is to be done in collaboration with another institution, provide information on the institution and why it is to do the specific component of the project. Further information on any such arrangements is to be given in the sections "Budget and Budget Explanation", "Biographical Sketches", and "Description of Facilities and Resources". 3.6 Literature Cited List all references cited in the narrative. Limit citations to current literature relevant to the proposed research. Information about each reference should be sufficient for it to be located by a reviewer of the proposal. 3.7 Budget and Budget Explanation A detailed budget is required for the entire project period, which normally will be three years, and for each fiscal year. It is preferred that DOE's budget page, Form 4620.1 be used for providing budget information*. Modifications of categories are permissible to comply with institutional practices, for example with regard to overhead costs. A written justification of each budget item is to follow the budget pages. For personnel this should take the form of a one-sentence statement of the role of the person in the project. Provide a detailed justification of the need for each item of permanent equipment. Explain each of the other direct costs in sufficient detail for reviewers to be able to judge the appropriateness of the amount requested. Further instructions regarding the budget are given in section 4 of this guide. * Form 4620.1 is available at web site: http://www.sc.doe.gov/production/grants/forms.html 3.8 Other Support of Investigators Other support is defined as all financial resources, whether Federal, non-Federal, commercial or institutional, available in direct support of an individual's research endeavors. Information on active and pending other support is required for all senior personnel, including investigators at collaborating institutions to be funded by a subcontract. For each item of other support, give the organization or agency, inclusive dates of the project or proposed project, annual funding, and level of effort devoted to the project. 3.9 Biographical Sketches This information is required for senior personnel at the laboratory submitting the proposal and at all subcontracting institutions. The biographical sketch is limited to a maximum of two pages for each investigator. 3.10 Description of Facilities and Resources Describe briefly the facilities to be used for the conduct of the proposed research. Indicate the performance sites and describe pertinent capabilities, including support facilities (such as machine shops) that will be used during the project. List the most important equipment items already available for the project and their pertinent capabilities. Include this information for each subcontracting institution, if any. 3.11 Appendix Include collated sets of all appendix materials with each copy of the proposal. Do not use the appendix to circumvent the page limitations of the proposal. Information should be included that may not be easily accessible to a reviewer. Reviewers are not required to consider information in the Appendix, only that in the body of the proposal. Reviewers may not have time to read extensive appendix materials with the same care as they will read the proposal proper. The appendix may contain the following items: up to five publications, manuscripts (accepted for publication), abstracts, patents, or other printed materials directly relevant to this project, but not generally available to the scientific community; and letters from investigators at other institutions stating their agreement to participate in the project (do not include letters of endorsement of the project).
4. Detailed Instructions for the Budget 4.1 Salaries and Wages List the names of the principal investigator and other key personnel and the estimated number of person-months for which DOE funding is requested. Proposers should list the number of postdoctoral associates and other professional positions included in the proposal and indicate the number of full-time-equivalent (FTE) person-months and rate of pay (hourly, monthly or annually). For graduate and undergraduate students and all other personnel categories such as secretarial, clerical, technical, etc., show the total number of people needed in each job title and total salaries needed. Salaries requested must be consistent with the institution's regular practices. The budget explanation should define concisely the role of each position in the overall project. 4.2 Equipment DOE defines equipment as "an item of tangible personal property that has a useful life of more than two years and an acquisition cost of $25,000 or more." Special purpose equipment means equipment which is used only for research, scientific or other technical activities. Items of needed equipment should be individually listed by description and estimated cost, including tax, and adequately justified. Allowable items ordinarily will be limited to scientific equipment that is not already available for the conduct of the work. General purpose office equipment normally will not be considered eligible for support. 4.3 Domestic Travel The type and extent of travel and its relation to the research should be specified. Funds may be requested for attendance at meetings and conferences, other travel associated with the work and subsistence. In order to qualify for support, attendance at meetings or conferences must enhance the investigator's capability to perform the research, plan extensions of it, or disseminate its results. Consultant's travel costs also may be requested. 4.4 Foreign Travel Foreign travel is any travel outside Canada and the United States and its territories and possessions. Foreign travel may be approved only if it is directly related to project objectives. 4.5 Other Direct Costs The budget should itemize other anticipated direct costs not included under the headings above, including materials and supplies, publication costs, computer services, and consultant services (which are discussed below). Other examples are: aircraft rental, space rental at research establishments away from the institution, minor building alterations, service charges, and fabrication of equipment or systems not available off-the-shelf. Reference books and periodicals may be charged to the project only if they are specifically related to the research. a. Materials and Supplies The budget should indicate in general terms the type of required expendable materials and supplies with their estimated costs. The breakdown should be more detailed when the cost is substantial. b. Publication Costs/Page Charges The budget may request funds for the costs of preparing and publishing the results of research, including costs of reports, reprints page charges, or other journal costs (except costs for prior or early publication), and necessary illustrations. c. Consultant Services Anticipated consultant services should be justified and information furnished on each individual's expertise, primary organizational affiliation, daily compensation rate and number of days expected service. Consultant's travel costs should be listed separately under travel in the budget. d. Computer Services The cost of computer services, including computer-based retrieval of scientific and technical information, may be requested. A justification based on the established computer service rates should be included. e. Subcontracts Subcontracts should be listed so that they can be properly evaluated. There should be an anticipated cost and an explanation of that cost for each subcontract. The total amount of each subcontract should also appear as a budget item. 4.6 Indirect Costs Explain the basis for each overhead and indirect cost. Include the current rates. |