Notice requesting Applications for DOE Health Effects Research

stodolsk at stodolsk at
Tue Apr 28 09:18:22 EST 1992

Department of Energy 
Office of Energy Research
Special Research Grant Program Notice 92-16:  Health Effects
AGENCY:  Department of Energy (DOE)
ACTION:  Notice inviting grant applications

SUMMARY:  The Office of Health and Environmental Research (OHER)
of the Office of Energy Research (ER), U.S. Department of Energy,
hereby announces its interest in receiving applications for
Special Research Grants in support of the Health Effects Research
Program.  The primary objective of this Program is to develop the
information base necessary to identify, understand, anticipate,
and mitigate the health consequences of exposure to energy-related
agents (e.g., radiation or chemical).  The Program examines
radiological and chemical effects at all levels of biology
including molecular, cellular, tissue/organ, and whole animals;
and it uses these findings to develop a mechanistic understanding
of effects and to provide the information necessary for predicting
risk from exposure.  The biological resources and the new
technologies that are being developed in the Human Genome Program
are revolutionizing the ability to detect and quantify genetic
damage leading to mutations, tumors, and other health endpoints. 
The DOE is seeking applications that exploit these technological
advances and that provide new information that can be used to gain
a better understanding of impacts on humans who are exposed to
low-dose radiation and/or toxic chemicals.  While the research
covered by this Program is broad in scope, the current
solicitation is seeking preapplications primarily in the following
three areas:  (1) DNA repair; (2) cellular and molecular
mechanisms of carcinogenesis (especially those using human cell
systems); and (3) low dose radiation studies, <10cGy, that will
improve our understanding of the dose effect relationships at low

Before preparing a formal application, potential applicants are
encouraged to first submit a brief preapplication in accordance
with 10 CFR 600.10(d)(2) which consists of two to three pages of
narrative describing the research project objectives and method of
accomplishment.  These will be reviewed relative to the scope and
the research needs of the Health Effects Research Program. 
Preapplications referencing Program Notice 92-16 should be
received by June 15, 1992, and sent to the following address:  Dr.
Marvin E. Frazier, Office of Health and Environmental Research,
ER-72 (GTN), Washington, D.C. 20585, (301) 903-5364, FAX (301)
903-7363.  Telephone and telefax numbers are required to be part
of a preapplication.  A response to the preapplications discussing
the potential programmatic relevance of a formal application will
be returned.

DATES:  Formal applications submitted in response to this Notice
must be received by 4:30 p.m., E.D.T., August 21, 1992, to be
accepted for merit review in October 1992 and to permit timely
consideration for award in Fiscal Year 1993.

ADDRESSES:  Formal applications referencing Program Notice 92-16
should be forwarded to:  U.S. Department of Energy, Office of
Energy Research, Acquisition and Assistance Management Division,
ER-64, Mail Stop G-236, Washington, D.C. 20585, ATTN:  Program
Notice 92-16.  The following address must be used when submitting
applications by U.S. Postal Service Express, any commercial mail
delivery service or when hand carried by the applicant:  U.S.
Department of Energy, Acquisition and Assistance Management
Division, ER-64, 19901 Germantown Road, Germantown, MD  20874.

FOR FURTHER INFORMATION CONTACT:  Dr. Marvin E. Frazier, Office of
Health and Environmental Research, ER-72 (GTN), Office of Energy
Research, U.S. Department of Energy, Washington, D.C. 20585, (301)

SUPPLEMENTARY INFORMATION:  Through this solicitation, DOE plans
to support new research in specific areas of interest that
include:  DNA repair, molecular mechanisms of carcinogenesis, and
mechanistic studies that examine the dose response relationship at
low doses (<10cGy).

With this notice DOE is soliciting grant applications to map,
clone, and investigate the biochemistry of human DNA repair genes. 
Research is needed that will examine the interactions between DNA
repair proteins, DNA, and other macromolecules in order to better
define the processes responsible for the repair or fixation of DNA
damage.  Better methods are also solicited for identifying and
characterizing new and modified gene products that are produced in
response to damage by physical and/or chemical agents.  The DOE is
also interested in the use of transgenic cell lines and transgenic
animals, in which repair-related genes have been mutagenized or
"knocked out", to measure their influence on normal processes of
growth and differentiation, genomic instability, gene expression,
and DNA repair.  The DOE is soliciting research
to improve assays for detecting, in humans, mutated DNA repair
genes (both homozygous and heterozygous) that may alter
susceptibility to DNA damaging agents.

The DOE is requesting research that elucidates the molecular and
cellular events underlying spontaneous and induced genetic and
epigenetic events that lead to cancer, heritable mutations, and/or
congenital malformations.  Priority will be given to the use of
human cell systems, e.g., stem cells and/or cells from transgenic
animals, for examining the effects of dose, dose rate and linear
energy transfer (LET) on viability, mutation induction,
chromosomal damage, DNA repair, cell transformation, and
progression to malignancy.

The most frequent radiation exposures for most people are low-
dose, low-dose-rate exposures.  The basic hypothesis of risk
assessors is that the frequency of low level radiation effects
increases as a linear, non-threshold function with dose.  The DOE
is soliciting research that will test this hypothesis at levels of
<10cGy.  These studies can include examination of how the cellular
and molecular processes that lead to cancer are influenced by
dose, dose rate, or LET.  The DOE is also interested in effects of
radiation or chemicals on the genetic stability of exposed cells. 
Recent data suggests that clonal progeny of irradiated cells
exhibit a persistently elevated frequency of spontaneous mutations
and nonclonal chromosomal aberrations for many populations post-
irradiation.  It is important to understand the mechanism of these
effects, their role in carcinogenesis, and the exposures necessary
to trigger the response.

It is anticipated that approximately $2 million will be available
for grant awards during FY 1993, contingent upon availability of
appropriated funds.  Multiple year funding of grant awards is
expected, and is also contingent upon availability of funds. 
Previous awards have ranged from $90 thousand per year up to $400
thousand per year (total costs) with terms from 1 to 3 years. 
Most awards are in the $150 thousand to $300 thousand per year
(total costs) range for 3 years.  Similar award sizes are
anticipated for new grants.  Information about development and
submission of applications, eligibility, limitations, evaluation,
selection process, and other policies and procedures may be found
in the ER Application and Guide for the Special Research Grants
Program and 10 CFR Part 605.  ER, as part of its grant
regulations, requires at 10 CFR 605.11(b) that a grantee funded by
ER and 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" (51 FR 16958,
May 7, 1986), or such later revision of those guidelines as may be
published in the Federal Register.  The application kit and guide
is available from the U.S. Department of Energy, Acquisition and
Assistance Management Division,

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