[Federal Register Volume 64, Number 217 (Wednesday, November 10, 1999)]
[Notices]
[Pages 61318-61321]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-29440]
-----------------------------------------------------------------------
DEPARTMENT OF ENERGY
Office of Science
Office of Science Financial Assistance Program Notice 00-02;
Experimental and Computational Structural Biology
AGENCY: Office of Science, 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
[[Page 61319]]
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/
[[Page 61320]]
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 Part
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.
[[Page 61321]]
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 29, 1999.
John Rodney Clark,
Associate Director of Science for Resource Management.
[FR Doc. 99-29440 Filed 11-9-99; 8:45 am]
BILLING CODE 6450-01-P
