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Office of Science
Notice 00-02
Experimental and Computational Structural Biology
Department of Energy
Office of Science
Office of Science Financial Assistance Program Notice 00-02:
Experimental and Computational Structural Biology
AGENCY: U.S. Department of Energy (DOE)
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), hereby announces its interest in receiving grant applications
in its Experimental and Computational Structural Biology Program.
Research is sought for experimental and computational biological
studies on the structural biology of proteins involved in DNA repair
or in bioremediation.
DATES: Before preparing a formal application, potential
applicants are encouraged to submit a brief preapplication. All
preapplications, referencing Program Notice 00-02, should be received
by DOE by 4:30 P.M., E.S.T., January 12, 2000. A response encouraging
or discouraging the submission of a formal application will be communicated
by electronic mail by January 25, 2000.
Formal applications submitted in response to this notice must
be received by 4:30 P.M., E.S.T., May 2, 2000, to be accepted for
merit review and consideration for award in Fiscal Years 2000 and
2001.
ADDRESSES: Preapplications referencing Program Notice 00-02,
must be sent by E-mail to sharon.betson@science.doe.gov. Preapplications
will also be accepted if mailed to the following address: Ms. Sharon
Betson, Office of Biological and Environmental Research, SC-73,
19901 Germantown Road, Germantown, Maryland 20874-1290.
Formal applications, referencing Program Notice 00-02, should
be forwarded to: U.S. Department of Energy, Office of Science, Grants
and Contracts Division, SC-64, 19901 Germantown Road, Germantown,
Maryland 20874-1290, ATTN: Program Notice 00-02. This address must
also be used when submitting applications by U.S. Postal Service
Express Mail or any other commercial overnight delivery service,
or hand-carried by the applicant. An original and seven copies of
the application must be submitted.
FOR FURTHER INFORMATION CONTACT: Dr. Roland F. Hirsch,
Office of Biological and Environmental Research, SC-73, U.S. Department
of Energy, 19901 Germantown Road, Germantown, MD 20874-1290, telephone:
(301) 903-9009, FAX: (301) 903-0567, E-mail: roland.hirsch@science.doe.gov.
Concerning the DNA Damage Recognition and Repair aspects: Dr. David
G. Thomassen, Office of Biological and Environmental Research, SC-72,
U.S. Department of Energy, 19901 Germantown Road, Germantown, MD
20874-1290, telephone: (301) 903-9817, FAX: (301) 903-8521, E-mail:
david.thomassen@science.doe.gov. Concerning the Bioremediation aspects:
Dr. Anna C. Palmisano, Office of Biological and Environmental Research,
SC-73, U.S. Department of Energy, 19901 Germantown Road, Germantown,
MD 20874-1290, telephone: (301) 903-9963, FAX: (301) 903-8519, E-mail:
anna.palmisano@science.doe.gov. The full text of Program Notice
00-02 is available via the Internet using the following web site
address:
http://www.sc.doe.gov/production/grants/grants.html.
SUPPLEMENTARY INFORMATION: The Office of Biological and
Environmental Research supports a directed, basic research program
in the areas of environmental, life and medical science. Major research
program emphases are placed on characterization of human and microbial
genomes, model organisms for understanding human gene function,
structural biology, the biological effects of low dose radiation,
global change, science and technology for environmental remediation,
advanced imaging technologies, biomedical engineering and molecular
nuclear medicine.
Nucleic acid and derived amino acid sequence data are flowing
from genome projects at an accelerating rate. Utilizing the genomic
sequence as a blueprint, large-scale high-throughput three-dimensional
structural analysis of cell proteins is planned. However, knowledge
of high resolution protein structure will not be sufficient for
understanding of protein function in the cellular environment. Proteins
do not act independently or statically in living systems. In carrying
out their functions within cells, proteins form complexes with other
proteins and interact with a variety of structural, regulatory and
ligand molecules. The role of structure in determining protein interactions
with diverse molecules in a cell is still poorly understood. It
is necessary to observe dynamic changes in protein structure and
to study protein modifications, translocation, and subcellular concentrations
to fully understand protein function. Such studies are therefore
a major focus of this program.
The transformation of the accumulating database of genomic information
into a practical understanding of structure-function relationships
in biological macromolecules and of the complicated systems that
constitute living cells, tissues and organisms is paramount. The
ultimate goal is to extend the understanding of the function and
behavior of individual proteins to the genome scale through escalating
levels of complexity from functional aggregates to metabolic circuits
and homeostatic networks. This approach will eventually lead to
a systems view of biology. This will enable diverse applications
in human health, including individualized medicine and drug design,
in biotechnology, including, new and improved biomaterials and new
biocatalysis in industry and manufacturing, in environmental science
for the design of enzymes for effective and efficient removal of
environmental contaminants and in energy technology for the development
and conversion of biomass for fuels.
This notice is to solicit applications for grants for experimental
and computational structural biology studies to expand our understanding
of the function of proteins and protein complexes relevant to two
high priority research programs within the Office of Biological
and Environmental Research: 1) Recognition and repair of DNA damage,
and 2) Bioremediation of environmental contamination by metals and
radionuclides.
DNA Damage Recognition and Repair
The Office of Biological and Environmental Research has a long
standing interest in determining health risks from exposures to
low levels of radiation, information that is critical to adequately
and appropriately protect people and to make the most effective
use of our national resources. The Low Dose Radiation Research Program
(see
http://www.sc.doe.gov/production/ober/lowdose.html), supports
research on the recognition and repair of DNA damage induced by
low doses of ionizing radiation. Understanding cellular DNA damage
recognition and repair in response to low doses of radiation is
a key component of determining health risks from low doses of radiation
and is likely to be a significant factor in identifying genetic
factors that determine individual sensitivity to low doses of radiation.
The Office of Biological and Environmental Research will accept
applications to study proteins involved in the recognition and repair
of radiation-induced DNA damage in prokaryotes and eukaryotes (including
humans). Studies of interest include the following:
- High-resolution three-dimensional structure of normal and mutated
DNA damage recognition and repair proteins using X-ray crystallography
and NMR with an emphasis on structure/function relationships.
- Dynamic changes in protein structure associated with protein
modification and with protein-protein and protein-DNA interactions
that occur during the recognition and repair of radiation-induced
DNA damage.
- Imaging of multi-protein DNA damage recognition and repair complexes,
including high resolution, real-time optical imaging.
- Precise measurements of DNA damage recognition and repair protein
concentrations, intracellular compartmentalization, and translocations
in response to ionizing radiation.
Bioremediation
The Office of Biological and Environmental Research supports bioremediation
research in its Natural and Accelerated Bioremediation Research
Program (NABIR) (see http://www.sc.doe.gov/production/ober/EPR/nabir.html
and http://www.lbl.gov/NABIR/).
The major focus of this program is to gain a better understanding
of the fundamental biological, chemical, geological, and physical
processes that must be marshaled for the development and advancement
of new, effective, and efficient processes for the remediation and
restoration of the Nation's nuclear weapons production sites. A
particular goal is to use molecular and structural biology to enable
understanding of potential microbial remediation processes and to
genetically modify macromolecules and organisms to improve their
bioremedial activities. Many molecules, enzymes, and enzyme pathways
that may be effective for bioremediation of metals and radionuclides
are being identified.
The Office of Biological and Environmental Research will accept
applications for structural biological studies in the area of bioremediation,
particularly those concerned with the reduction of metals and radionuclides
in microbes (e.g., Shewanella putrefaciens MR 1). Studies of interest
include the following:
- High resolution three dimensional structure of proteins involved
in critical functions of microorganisms relevant to bioremediation
processes, particularly those proteins involved in reducing metals
and radionuclides. Structure/function relationships should be
stressed.
- Dynamic changes in protein structure related to the binding
and reduction of metals and radionuclides.
- Realtime visualization of protein complexes involved in these
bioremediation functions.
- Studies, comparable to those outlined above, on genetically
modified proteins and protein complexes with potential to contribute
to the bioremediation of metals and radionuclides.
Computational Structural Biology
The Office of Biological and Environmental Research is interested
in the development of improved computational approaches for finding
the proteins involved in DNA repair or in bioremediation processes,
for predicting the three dimensional structures of these proteins,
or for modeling the complex interactions of these proteins in living
organisms. Computational approaches to predict protein structure
and function will play an increasingly important role as the complete
genomic sequences of more organisms, including human, are made available
over the next few years. These computational approaches will also
provide an important interface with the projected increases in the
rate of protein structure determination. This program is focusing
on sophisticated prediction, modeling, and simulation research to
provide a generalizable approach to the interrelationship of macromolecular
sequence, structure, and function with specific applications in
DNA repair or in bioremediation.
The program places emphasis on projects that advance or integrate
existing software tools in novel ways and/or develop new computational
strategies to exploit databases of macromolecular structural information,
including both high and low resolution. This includes the goal of
predicting the structure and function of newly discovered gene sequences
as well as the prediction or computational design of the chemical
properties and architectural arrangement of proteins, protein-protein
complexes, or protein-nucleic acid complexes needed for a particular
functional application.
The Office of Biological and Environmental Research will accept
applications for the development and use of computational tools
that would ultimately accomplish one or more of the following objectives.
A clear path should be presented from the fundamental computational
research to be carried out to the testing of the new algorithms
on one or more of these objectives:
- Develop high throughput computational methods to predict or
identify, from sequence information, proteins involved in the
recognition or repair of radiation- induced DNA damage or in the
bioremediation of metals and radionuclides. This predictive capability
will be essential for understanding the complete structure, function,
and dynamic behavior of multiprotein complexes.
- Predict from sequence the structure or the function of proteins
involved in the recognition or repair of radiation-induced DNA
damage or in the bioremediation of metals and radionuclides.
- Characterize or simulate molecular interactions between proteins,
proteins and DNA, or proteins and ligand molecules involved in
the recognition or repair of radiation- induced DNA damage or
in the bioremediation or metals and radionuclides including changes
due to genetically modified proteins.
Program Funding
It is anticipated that up to $3 million will be available for
multiple grant awards during Fiscal Years 2000 and 2001 contingent
upon the availability of appropriated funds. Applications may request
project support up to three years, with out-year support contingent
on the availability of funds, progress of the research and programmatic
needs. We expect to award several research grants of up to $300,000
per year in this area.
Preapplications
A brief preapplication should be submitted. The preapplication
should identify, on the cover sheet, the title of the project, the
institution, principal investigator name, address, telephone, fax,
and E-mail address, and the research element(s) being addressed
(DNA Damage Recognition and Repair; Bioremediation; or Computational
Structural Biology). The preapplication should consist of two to
three pages identifying and describing the research objectives,
methods for accomplishment, and potential benefits of the effort.
Preapplications will be evaluated relative to the scope and research
needs for the Experimental and Computational Structural Biology
Program.
Applications
Applications will be subjected to scientific merit review (peer
review) and will be evaluated against the following evaluation criteria
listed in descending order of importance as codified at 10 CFR 605.10(d):
1. Scientific and/or Technical Merit of the Project
2. Appropriateness of the Proposed Method or Approach
3. Competency of Applicant's Personnel and Adequacy of Proposed
Resources
4. Reasonableness and Appropriateness of the Proposed Budget.
The evaluation will include program policy factors such as the relevance
of the proposed research to the terms of the announcement and the
agency's programmatic needs. Note, 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.
Information about the development, submission of applications,
eligibility, limitations, evaluation, the selection process, and
other policies and procedures may be found in 10 CFR Part 605, and
in the Application Guide for the Office of Science Financial Assistance
Program. Electronic access to the Guide and required forms is made
available via the World Wide Web at:
http://www.sc.doe.gov/production/grants/grants.html. In addition,
for this notice, the Project Description must be 25 pages or less,
exclusive of attachments, and the application must contain a Table
of Contents, an abstract or project summary, letters of intent from
collaborators (if any), and short curriculum vitae consistent with
National Institutes of Health guidelines. On the SC grant face page,
form DOE F4650.2, in block 15, also provide the PI's phone number,
fax number, and E-mail address.
DOE policy requires that potential applicants adhere to 10 CFR
745 “Protection of Human Subjects”, or such later revision of those
guidelines as may be published in the Federal Register.
The Office of Science as part of its grant regulations requires
at 10 CFR 605.11(b) that a recipient receiving a grant and performing
research involving recombinant DNA molecules and/or organisms and
viruses containing recombinant DNA molecules shall comply with NIH
"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 Catalog of Federal Domestic Assistance Number for this program
is 81.049, and the solicitation control number is ERFAP 10 CFR Part
605.
John Rodney Clark
Associate Director of Science
for Resource Management
Published in the Federal Register November 10,1999, Volume 64,
Number 217, Pages 61318-61321.
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