[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 [email protected]. 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: [email protected]. 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: 
[email protected]. 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: 
[email protected]. 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