[Federal Register Volume 65, Number 161 (Friday, August 18, 2000)]
[Notices]
[Pages 50510-50513]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-21123]


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DEPARTMENT OF ENERGY


Office of Science Financial Assistance Program Notice 00-18; 
Microbial Genome Program

AGENCY: U.S. Department of Energy (DOE).

ACTION: Notice inviting grant applications.

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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 applications for grants in support 
of the Microbial Genome Program (MGP), focused on microbes of interest 
to the DOE, e.g. those involved in environmental processes, including 
waste remediation, carbon management, energy production and 
biotechnology. This announcement is focused on (1) whole genome 
functional analyses of genomic information from microorganisms; (2) 
bioinformatics tools for microbial genome annotation; (3) 
characterization of microbial genomic plasticity, e.g. lateral gene 
transfers and other forms of genomic information transfer; (4) novel 
technologies for comparative microbial genome sequencing that exploit 
previously sequenced microbial genomes; and (5) technologies to assess 
consortia and environmental diversity of hard-to-culture microbes. This 
announcement represents a significant departure from past MGP 
announcements in that the DOE will not solicit applications to continue 
high throughput sequencing of microbial genomes. Rather, this is a 
shift in emphasis to exploiting already sequenced genomes to address 
DOE mission needs.

DATES: Preapplications referencing Program Notice 00-18 should be 
received by October 2, 2000.
    Formal applications in response to this notice should be received 
by 4:30 p.m., e.s.t., December 14, 2000, to be accepted for merit 
review and funding in FY 2001.

ADDRESSES: Preapplications referencing Program Notice 00-18 should be 
sent to Dr. Daniel W. Drell, Office of Biological and Environmental 
Research, SC-72, Office of Science, U.S. Department of Energy, 19901 
Germantown Road, Germantown, MD 20874-1290; e-mail is acceptable for 
submitting preapplications using the following address: 
[email protected].
    Formal applications referencing Program Notice 00-18, should be 
forwarded 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 00-18. This address must be used when 
submitting applications by U.S. Postal Service Express Mail or any 
commercial mail delivery service, or when hand-carried by the 
applicant.

FOR FURTHER INFORMATION CONTACT: Dr. Daniel W. Drell, SC-72, Office of 
Biological and Environmental Research, Office of Science, U.S. 
Department of Energy, 19901 Germantown Road, Germantown, MD 20874-1290, 
telephone: (301) 903-4742, e-mail: [email protected]. The 
full text of Program Notice 00-18 is available via the Internet using 
the following web site address: http://www.sc.doe.gov/production/grants/grants.html.

SUPPLEMENTARY INFORMATION: The Microbial Genome Program (MGP) supports 
key DOE business areas by providing microbial DNA sequence information 
that will further the understanding and application of microbiology 
relating to energy production, chemical and materials production, 
environmental carbon management, and environmental cleanup. The 
elucidation of microbial genome sequences is a natural outgrowth of 
past and current Biological and Environmental Research (BER) Programs, 
including DNA sequencing from the Human Genome Program, structural 
biology studies utilizing BER-supported facilities and synchrotrons 
located at DOE laboratories, and molecular microbiological research 
supported by BER environmental programs. The MGP benefits directly from 
capabilities at DOE national laboratories, DOE and National Institutes 
of Health Human Genome Centers, the National Center for Biotechnology 
Information (NCBI) at the National Institutes of Health (NIH), and the 
capabilities of universities and non-profits. The MGP represents a 
considerable interdisciplinary effort and will contribute to and draw 
from a wide variety of public and private programs. Over the last 5 
years, sequencing of microorganisms that live in extreme environments 
(including the deep subsurface, geothermal environments, hypersaline 
environments, high-radiation environments, and toxic waste sites) has 
provided a considerable information base for scientific research 
related not only to DOE missions but also to other federal agency 
missions, and U.S. industry. Applications are now being sought in five 
complementary areas: whole-genome functional analyses, bioinformatics 
applied to

[[Page 50511]]

microbial genome sequences, characterization of microbial genomic 
plasticity, novel microbial sequencing approaches, and the 
characterization of the diversity of microbial consortia and/or hard-
to-culture microbes that mediate processes of relevance to the DOE. 
Each application must clearly state which area is being addressed; if 
an applicant wishes to address more than one area, the application must 
clearly describe the expected advantages of an integrated approach.
    Candidate microorganisms for study can comprise archaea, bacteria, 
or communities made up of bacteria and/or archaea that mediate or 
catalyze metabolic events of energy or environmental importance. 
Preference will be given to those applicants using microbes for which 
complete or near-complete genomic sequencing information in the public 
domain exists. (See http://www.ornl.gov/microbialgenomes/organisms.html 
for a current list of microbes that have been and are being sequenced.) 
Priority will be given to studies on those microbes that can 
bioremediate metals and radionuclides, microbes that can degrade 
significant biopolymers such as celluloses and lignins or microbes that 
are involved in environmental carbon management, e.g. fix or sequester 
CO2. Finally, microbes that participate in consortia with 
already-sequenced species are of interest. Strict pathogens or 
parasites will not be considered.
    (1) Functional Analysis. It is presently difficult, and in many 
instances impossible, to predict biological function from microbial 
genomic sequence data, even when the entire genome has been sequenced 
and published and is available for inspection. Better experimental and 
computational methods are needed to identify novel open reading frames 
and predict their functions at a whole-genome scale, particularly from 
completely sequenced microbial genomes. Accordingly, applications are 
requested that will develop better ways to interpret sequence data from 
novel open reading frames, and even whole genomes, using both 
comparative genomic approaches as well as novel analyses. The DOE MGP 
is particularly interested in the use of sequence data for whole genome 
approaches to functional prediction, functional regulation, functional 
categorization (e.g. transporters, environmental sensors, redox 
enzymes, cytoskeletal components, DNA repair systems, metal reductases, 
biodegradative enzymes, etc.) as well as those approaches that identify 
and distinguish rare or unique ORFs that can be linked to restricted 
environmental niches or DOE-relevant bioremediation capacities. 
Identification of domains in gene sequences that mediate protein-
protein interactions are also of great interest. Applicants should 
focus on microbes of mission interest to the DOE, as described above. 
It is estimated that between four and six awards for a total of up to 
$1 million could be available for this area in FY 2001, contingent upon 
the availability of appropriated funds.
    (2) Bioinformatics. It is estimated that by December 2000, 
completed genomic sequences of perhaps 50 archaea and bacteria will be 
publicly available, more than a third of them as a direct result of DOE 
Microbial Genome Program funding. In June 2000, a draft sequence for 
the entire human genome became available as well. For several microbes, 
complete sequences of close evolutionary relatives now or will soon 
exist. Computational comparative genomics can illuminate evolutionary 
pathways to complement traditional phenotype-based analyses, provide 
data for the prediction of gene function between organisms, and 
contribute to modeling pathways. The value of such comparative 
functional analysis is highlighted by the remarkable frequency of novel 
open reading frames in microbial genome sequences (up to half the genes 
in many cases) that currently lack any annotation. The evolutionary 
conservation of open reading frames and certain protein functions 
between microbes and more complex organisms (including human) 
emphasizes the value of microbial sequences for understanding the 
functions of uncharacterized microbial (and, potentially, human) genes. 
To this end, computational methods for interspecies genomic comparisons 
are an area of particular interest for this solicitation. Applications 
are requested that propose ways in which microbial sequence data from 
all sources can be analyzed, compared, annotated, and used to predict 
the function of homologous genes in both prokaryotic and eukaryotic 
organisms. Thus, this notice solicits applications for research into:

    (a) Novel computational tools to increase the value of microbial 
genomic information, such as improved techniques for identifying 
distant sequence homologies, reconstructing phylogenetic trees, 
predicting gene function, or identifying and modeling gene 
expression networks, and
    (b) Algorithms and tools to extract longer stretches, and make 
more accurate base calls from current sequencing procedures in order 
to assist the closure process for microbial genomes.

    Of special interest will be methods that use unique DOE resources 
in massively parallel, high-capacity supercomputers (machines in the 
multi-teraflop range). It is expected that computational tools 
developed under these awards will be widely distributed to the 
scientific community (e.g. via a WWW site) and some level of user 
support will be available. It is anticipated that between three and six 
awards for a total of up to $2 million could be available for this area 
in FY 2001, contingent upon the availability of appropriated funds.
    (3) Characterization of Microbial Genomic Plasticity. Completed 
sequences for several microbes (e.g. Thermotoga maritima, (Nelson, K. 
et al. (1999) Nature 399: 323-329) and Deinococcus radiodurans (White, 
O., et al. Science (1999) 286: 1571-1577) strongly suggest that entire 
blocks of genes have been laterally transferred during microbial 
evolution, even from sources in different biological kingdoms. How 
widespread this phenomenon may be, or any evolutionary constraints on 
it, is unknown. Applications are solicited that would assess lateral 
gene exchanges, in terms of its frequency in different environmental 
niches, the mechanisms involved, as well as the circumstances in which 
it is observed. It is anticipated that between two and four awards 
totaling up to $1 million could be available for this area in FY 2001, 
contingent upon the availability of appropriated funds.
    (4) Novel Approaches to Microbial Genomic Sequencing. Many 
microorganisms that are closely related by means of phylogenetic 
measures (e.g., 16S rRNA comparisons) display dramatic differences in 
phenotypic characteristics. Such differences can be chromosomal in 
origin, or they can be due to extrachromosomal genetic elements. The 
DOE MGP is interested in novel comparative sequencing approaches that 
exploit the completed sequence of one microorganism to efficiently 
determine the sequence of a related taxon or species.
    This element of this solicitation could contribute to:
    (a) New methods to accelerate genomic comparisons, without 
resequencing the entire genome of the related organism de novo 
(technologies up to the proof-of-principle stage are eligible for 
support). Technologies responsive to this element of this solicitation 
should be firmly grounded in already completed microbial sequencing 
projects; these may include subtractive hybridization approaches, or 
``DNA chips'', among others, but it is not the aim of this solicitation 
to

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support completely untested technologies;
    (b) strategies to more efficiently identify specific sequence 
features associated with phenotypic differences; and
    (c) techniques to characterize and quantify lateral gene transfer 
(especially any correlation with environmental selection).
    A plan for making comparative sequence data publicly available by 
deposition into a community-accessible sequence database within three 
months of data acquisition must be included. A plan for efficient and 
timely annotation must be included in the Project Description. DOE 
expects that grantees will make all good faith efforts to publish in 
the open scientific literature the results of their funded work, 
including the genome sequences of microbes sequenced under this notice. 
(DOE data release requirements, a condition of any award, are available 
at: http://www.sc.doe.gov/production/ober/EPR/data.html). Applicants 
are encouraged to create process- and cost-effective partnerships that 
will maximize sequence data production and analysis, data 
dissemination, and progress towards understanding basic biological 
mechanisms that can further the development of biotechnology. It is 
anticipated that between two and four awards totaling up to $1 million 
could be available for this area in FY 2001, contingent upon the 
availability of appropriated funds.
    (5) Consortia and Hard-to-Culture Microbes. Most of our current 
knowledge of microbiology is derived from individual species that 
either cause diseases or grow easily and readily as monocultures under 
laboratory conditions and are thus easy to study. The preponderance of 
species in the environment does neither and is thus largely unknown to 
science. Most are thought to grow as part of interdependent consortia 
in which one species supplies a nutrient necessary for the growth of 
another. Virtually nothing is known of the organization, membership, or 
functioning of these consortia, especially those involved in 
environmental processes in which DOE is interested. Technologies are 
sought that enable genomic analyses of microbial consortia as well as 
analyses of the genomic information content and diversity of those 
species that have proven refractory to laboratory culture but are 
plentiful in environments challenged with metal and radionuclide 
wastes, or involved in carbon sequestration. It is anticipated that 
between two and three awards totaling up to $1 million could be 
available for this area in FY 2001, contingent upon the availability of 
appropriated funds.

Preapplications

    Potential applicants are strongly encouraged to submit a brief 
preapplication that consists of two to three pages of narrative 
describing the research objectives and technical approach(s). 
Preapplications will be reviewed relative to the scope and research 
needs of the OBER Microbial Genome Program, as outlined in the summary 
paragraph and in the SUPPLEMENTARY INFORMATION. The preapplication 
should identify, on the cover sheet, the title of the project, the 
institution, principal investigator name, telephone, fax, and e-mail 
address. A response to each preapplication discussing the potential 
programmatic relevance of a formal application will be communicated to 
the Principal Investigator within 14 to 21 days of receipt. Any renewal 
applications must include a list of publications resulting from 
previous DOE Microbial Genome Program funding.

Program Funding

    It is anticipated that up to $6 million will be available for all 
MGP awards in Fiscal Year 2001 from twelve to as many as twenty five 
awards are anticipated, contingent on availability of appropriated 
funds in FY 2001 and the size of the awards. Multiple year funding is 
expected, also contingent on availability of funds and progress of the 
research. Awards are expected to range from $200,000 to $1 million per 
year, total costs, with terms of one to three years.

Merit Review

    Applications will be subjected to scientific merit review (peer 
review) and will be evaluated against the following evaluation criteria 
which are listed in descending order of importance 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 will often be 
used, and submission of an application constitutes agreement that this 
is acceptable to the investigator(s) and the submitting institution.

Submission Information

    The Project Description must be 20 pages or less, exclusive of 
attachments. It must contain an abstract or project summary on a 
separate page with the name of the applicant, mailing address, phone 
FAX and E-mail listed. The application must include letters of intent 
from collaborators (briefly describing the intended contribution of 
each to the research), and short curriculum vitaes, consistent with NIH 
guidelines, for the applicant and any co-PIs.
    To provide a consistent format for the submission, review and 
solicitation of grant applications submitted under this notice, the 
preparation and submission of grant applications must follow the 
guidelines given in the Application Guide for the Office of Science 
Financial Assistance Program, 10 CFR Part 605. Access to SC's Financial 
Assistance Application Guide is possible via the World Wide Web at: 
http://www.sc.doe.gov/production/grants/grants.html.
    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 (10 CFR 
605.11(b)) requires that a grantee funded by SC and performing research 
involving recombinant DNA molecules and/or organisms and viruses 
containing recombinant DNA molecules shall comply with the 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.

Other Useful Web Sites Include

MGP Home Page--http://www.er.doe.gov/production/ober/microbial.html
DOE Joint Genome Institute Microbial Web Page--http://www.jgi.doe.gov/
JGI__microbial/html/
GenBank Home Page--http://www.ncbi.nlm.nih.gov/
Human Genome Home Page--http://www.ornl.gov/hgmis

    The Catalog of Federal Domestic Assistance Number for this 
program is

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81.049, and the solicitation control number is ERFAP 10 CFR Part 
605.

    Issued in Washington, DC on July 9, 2000.
John Rodney Clark,
Associate Director of Science for Resource Management.
[FR Doc. 00-21123 Filed 8-17-00; 8:45 am]
BILLING CODE 6450-01-U