[Federal Register Volume 67, Number 23 (Monday, February 4, 2002)]
[Notices]
[Pages 5095-5099]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-2597]


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DEPARTMENT OF ENERGY


Office of Science Financial Assistance Program Notice 02-13; 
Genomes to Life

AGENCY: Department of Energy.

ACTION: Notice inviting grant applications.

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SUMMARY: The Office of Biological and Environmental Research (OBER) and 
the Office of Advanced Scientific Computing Research (ASCR) of the 
Office of Science (SC), U.S. Department of Energy (DOE), hereby 
announce their interest in receiving applications for research from 
large, well integrated, multidisciplinary research teams (see 
SUPPLEMENTARY INFORMATION below) that support the Genomes to Life 
research program (http://www.doegenomestolife.org/). A central theme of 
the entire Genomes to Life program is to develop the necessary 
experimental and computational capabilities to enable a predictive 
understanding of the behavior of microbes and microbial communities of 
interest to DOE. To this end, proposals that integrate strong 
experimental biology and computational science research components are 
strongly encouraged. In such proposals, the leadership role may rest 
either with experimentation or with computation.

DATES: Statements of intent to apply, including information on 
collaborators and areas of proposed research and technology development 
should be submitted by March 1, 2002. Research applications are due by 
4:30 PM E.D.T. Tuesday May 7, 2002.

ADDRESSES: Statements of intent to apply should be sent to Ms. Joanne 
Corcoran by e-mail at [email protected] with copies to 
Dr. David Thomassen at [email protected] and Dr. Walter 
Polansky at [email protected]. Formal applications, 
referencing Program Notice 02-13, should be sent 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 02-13. 
This address must be used when submitting applications by U.S. Postal 
Service Express, commercial mail delivery service, or when hand carried 
by the applicant. (For safety reasons, the Washington, DC area 
continues to experience delays in the processing of all U.S. Mail. 
Please check the Office of Science, Grants and Contacts Web site at: 
www.sc.doe.gov/production/grants/grants.html for the latest updates 
regarding the processing of U.S. Mail.)

FOR FURTHER INFORMATION CONTACT: Dr. David Thomassen, telephone: (301) 
903-9817, e-mail: [email protected], Office of Biological 
and Environmental Research, SC-72, U.S. Department of Energy, 19901 
Germantown Road, Germantown, MD 20874-1290 and Dr. Walter Polansky, 
telephone: (301) 903-5800, e-mail: [email protected], 
Office of Advanced Scientific Computing Research, SC-31, U.S. 
Department of Energy, 19901 Germantown Road, Germantown, MD 20874-1290.
    A complementary request for proposals from DOE national laboratory 
led teams has been issued http://www.sc.doe.gov/production/grants/LAB02_13.html.

SUPPLEMENTARY INFORMATION:
    This solicitation will support the establishment of large, well 
integrated, multidisciplinary (e.g., biology, computer science, 
mathematics, computational science, engineering, informatics, 
biophysics, biochemistry) research teams. Applicants are invited to 
include, where appropriate, partners from multiple institutions, 
including DOE National Laboratories, universities, private research 
institutions, and companies. Successful applications will include a 
detailed management plan describing the responsibility of and 
relationship between all participating institutions and investigators, 
a strategy for maximizing communication and exchange of information 
between investigators, a data and information management plan, and 
project milestones.
    Research partners at individual universities, private research 
institutions and companies, and DOE National Laboratories will be 
funded directly by DOE but will be reviewed as part of the overall 
research application submitted by the lead research institution. To 
facilitate funding of individual non-laboratory research partners 
beginning in FY 2002, each application should include a complete set of 
forms for each non-laboratory research institution as described in the 
instructions contained in the Grant Application Guide, the Guide and

[[Page 5096]]

Forms are available on the Web at: http://www.sc.doe.gov/production/grants/grants.html. This includes:
     Signed Face Page (DOE F 4650.2 (10-91))
     Budgets for each year, (using DOE F 4620.1)
     Budget Explanation
     Biographical Sketches (limit 2 pages per senior 
investigator)
     Description of Facilities and Resources
     Current and Pending Support for each senior investigator
     Other institutional forms as described

Research Focus

    The Genomes to Life research program will cut across components of 
each of the goals described in the Genomes to Life program plan, 
available on the Web at: http://www.doegenomestolife.org/. Applicants 
should refer to the program plan for additional information on the 
overall organization of the Genomes to Life program. Individual 
applications should address one or more of the individual research 
elements described below.

Other useful Web sites include:
MCP Home Page--http://microbialcellproject.org.
Microbial Genome Program 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.

Microbes of Interest to DOE

    The initial focus of Genomes to Life should be on microbes 
(including fungi) directly relevant to DOE mission needs in energy 
(cleaner energy, biomass conversion, carbon sequestration), bioweapons 
defense (biothreat agents or their close relatives), or the environment 
(cleanup of metals and radionuclides at DOE sites). Research in Goals 1 
and 2 should take advantage of and focus on microbes whose complete DNA 
sequence is already known. Research in Goal 3 should focus on microbes 
or microbial communities of interest to, directly relevant to, or that 
would contribute substantially to an ability to address DOE mission 
needs. Selected, well-justified research using yeast may also be 
appropriate as a means of quickly generating data that addresses the 
needs of this solicitation and of the Genomes to Life Program. However, 
the use of yeast as a long-term research focus is not encouraged.

Data and Other Results

    Any data and results that are generated through the investigations 
into goals 1 through 4 that are appropriate to share with the broader 
community should be provided in timely, open, and machine-readable 
format where possible. Microbial DNA sequence data will be publicly 
released according to the ``Data Release Requirements: Microbial Genome 
Sequencing Projects'' (http://www.sc.doe.gov/production/ober/EPR/data.html). Plans should be included that describe the procedures and 
policies the teams will institute to make the data and results 
available and interoperable with other significant sources of relevant 
data. Any code development should be open source. Teams should be 
amenable to the adoption of open data standards and interoperability 
requirements, as they evolve and are specified by the Genomes to Life 
program.

Goal 1--Identify and Characterize the Molecular Machines of Life--
the Multiprotein Complexes that Execute Cellular Functions and 
Govern Cell Form

    Current structural genomics or proteomics efforts generally focus 
on individual proteins, either one at a time or at a genomic scale, or 
as pairs of interacting proteins. An initial focus of the Genomes to 
Life program will be to develop and implement research strategies and 
technologies that will enable the systematic identification, 
characterization, and, eventually, understanding of all the multi 
protein molecular machines in an organism. A research plan should be 
described that will lead, within five years, to the development of the 
capability to measure and characterize thousands of molecular machines 
per year. The initial focus of this research should be on microbial 
processes with application to DOE needs (see section on Microbes of 
Interest to DOE). The research plan should describe how the proposed 
research and technology and computational tool development will, within 
the next four to six years, enable at least 80% of the molecular 
machines in a single microbe to be identified and characterized within 
a single year.
    An overarching goal of the Genomes to Life program is to develop 
computational tools, based on experimental data, that enable us to 
predict the functions and behaviors of complex biological systems 
beginning with genome sequence data. In the context of Goal 1, 
computational tools are needed to predict the inventory of molecular 
machines, and the functions of those machines, likely to be found in a 
microbe whose DNA sequence is known. This could include development of 
computational modeling tools, including high performance 
implementations of techniques analogous to Rosetta-type algorithms and 
threading programs to characterize the molecular machinery on the scale 
of complete microbial organisms. Significant effort should be devoted 
to the development of high-precision computational models able to 
identify the principal components and functions of characterized 
molecular machines. These computational approaches will also provide an 
important future interface with the projected increases in the rate of 
protein structure determination to understand the molecular details of 
protein interactions in molecular machines.
    Milestones of progress and success should be included as part of 
the research plan. Pilot studies that test and compare several 
different research and technology strategies are encouraged along with 
a decision plan to choose and expand the most promising strategies.
    Understanding the role that these molecular machines play within an 
organism will require information on both the interactions of molecular 
machines and on the physical and temporal location and behavior of 
molecular machines within cells. Research plans should be described 
that will lead to high-throughput strategies, technologies, and 
computational tools for achieving these goals. Investigators conducting 
research on these goals should describe how they will work in close 
collaboration with or maintain a detailed awareness of the progress of 
investigators who are developing high-throughput strategies for 
identifying molecular machines. Pilot studies that test and compare 
several different research and technology strategies are encouraged 
along with a decision plan to choose and expand the most promising 
strategies.
    Experimental research is not being requested to determine the 
three-dimensional, high-resolution structure of individual proteins or 
multi protein molecular machines. As the number of high resolution 
protein structures in the Protein Data Bank increases dramatically over 
the next five years, that information will serve as an important 
starting point for characterizing the molecular details of protein-
protein interactions within and between individual molecular machines.

[[Page 5097]]

Goal 2--Characterize Gene Regulatory Networks

    Understanding the structure and function of an organism's molecular 
machines is a limited, though substantial, first step towards a 
predictive understanding of the organism's complex functions. This will 
only come by understanding the complex gene regulatory networks that 
govern the coordinated formation and behavior of molecular machines and 
their individual protein subunits. A goal of Genomes to Life is to 
develop large-scale research strategies, technologies, and 
computational tools needed to identify all the components of gene 
regulatory networks with an initial focus on cis-acting regulatory 
sequences. Although the principal focus should be on microbial 
processes with application to DOE needs (see section on Microbes of 
Interest to DOE), these studies will likely benefit from comparative 
genomics approaches that may cross species.
    Again, an overarching goal of the Genomes to Life program is to 
develop computational tools, based on experimental data, that enable us 
to predict the functions and behaviors of complex biological systems 
beginning with genome sequence data. In the context of Goal 2, 
computational tools are needed to predict regulatory networks for the 
molecular machines and their component proteins identified in Goal 1. A 
major goal is to be able to predict and reconstruct regulatory networks 
for molecular machines, metabolic pathways, or entire organisms 
beginning with knowledge of the organism's DNA sequence. Determination 
and verification of regulatory interactions will be enabled by the 
development of the integrated computational approaches assembling many 
types of experimental information together with relevant computational 
algorithms.
    These studies should be closely integrated with genome-scale 
proteomics efforts or efforts to identify all of an organisms's 
molecular machines and their dynamic behavior within cells. Pilot 
studies that test and compare several different research and technology 
strategies are encouraged along with a decision plan to choose and 
expand the most promising strategies.

Goal 3--Characterize the Functional Repertoire of Complex Microbial 
Communities in their Natural Environments at the Molecular Level

    Understanding the structure and functional capabilities and 
diversity of complex microbial communities is key to using the diverse 
functions and capabilities of microbes to address DOE mission needs. 
However, the majority of microbes of importance and interest to DOE 
have not been isolated, purified, and cultured. An initial goal of 
Genomes to Life is to use high throughput DNA sequencing and 
computational approaches to determine the genetic and functional 
diversity of individual uncultured microorganisms and of microbial 
communities. It is anticipated that the majority of high throughput DNA 
sequencing required for this Goal will be conducted at the DOE Joint 
Genome Institute. An estimate of the amount of DNA sequencing that will 
be required should be included as part of the application. Funds for 
high throughput DNA sequencing should not be included as part of the 
budget request for individual applications as funds will be provided 
directly to the Joint Genome Institute for Genomes to Life sequencing 
needs.
    The organisms and microbes chosen for sequencing should be chosen 
to help make an initial determination of:
     The extent and patterns of phylogenetic and genetic 
diversity in microbial communities from different environments.
     Whether microbial communities conserve metabolic function 
in spite of extensive individual phylogenetic diversity and whether a 
microbial community's metabolic functions correlate with the physical 
properties of its environmental niche.
     Improvements in the ability to infer the metabolic, 
physiologic, and behavioral characteristics of a microbe or microbial 
community from its DNA sequence (including improvements in the ability 
to infer gene function from DNA sequence).
    Just as development of computational tools to predict the 
inventory, functions, and regulation of molecular machines from genome 
sequence data is a key part of Goals 1 and 2, development of 
computational tools to predict the metabolic, physiologic, and 
behavioral characteristics of microbial communities from community DNA 
sequence data is a key part of Goal 3. It is expected that some of the 
computational tools developed will be executed on existing computer 
resources with little need for additional computational power. However, 
special consideration will be given to the development of computational 
tools that can be ported across high-performance computing 
environments, including computing capabilities that are not yet 
available but are expected soon.
    A scientific and experimentally based strategy for selecting the 
microbes and microbial communities proposed for analysis should be 
provided. Estimates of the number and diversity of uncultured microbes 
and microbial communities chosen for sequencing during the first three 
years of the project should be made. A strategy for estimating the 
degree of sequence coverage for DNA isolated from microbial communities 
should be provided.

Goal 4--Develop the Computational Methods and Capabilities to 
Advance Understanding of Complex Biological Systems and Predict 
Their Behavior

    Computational capabilities, including data management, modeling of 
complex biological systems, and prediction of biological responses, 
underpin all of Genomes to Life. In particular, the needs include:
     Computational research on analysis and modeling of the 
structure and function of molecular machines, as integrated with the 
research to be conducted under Goal 1 above, with an emphasis on the 
interactions among the proteins and other molecules that make up these 
machines. This could also include investigations into prediction of 
functions of the molecular machines through the use of consensus 
groupings or proxies, such as analogs to ``Rosetta'' or threading-type 
methods used for predicting the structure of single proteins.
     Computational research on models and simulations of 
metabolic pathways, regulatory networks, and whole-cell functions, as 
integrated with the research to be conducted under Goal 2 above. This 
may include computational tools to integrate data from a wide variety 
of high-throughput experimental data, such as mass spectrometry, 
protein arrays, cross linking, and Nuclear Magnetic Resonance data with 
other biological data, such as genome annotation and experimental 
genetic data, such as results from knockout experiments.
     Computational research in support of sequencing 
environmental samples to be conducted under Goal 3 above. Computational 
tools will be needed to analyze the output of the simultaneous 
sequencing of multiple organisms. This will include a need to infer 
properties of the environmental sample, such as the presence or absence 
of both certain classes of organisms and certain functional 
capabilities, such as particular metabolic pathways.
     Computational research in support of biological databases 
and database tool development. Any applications for

[[Page 5098]]

subprojects to augment or develop databases will be judged primarily on 
the degree that they contribute to the successful completion of the 
team's research conducted as part of Goals 1, 2, and 3 above. The 
subprojects will also be judged on the predicted utility of the 
database and tools to the broader community and to the degree that the 
tools contribute to the broader goal of database interoperability.
     It is expected that some of the computational tools 
developed in Goal 4 will be executed on existing computer resources 
with little need for additional computational power. Other tools may 
require particularly compute-intensive resources. Special consideration 
will be given to the development of computational tools that can be 
ported across high-performance computing environments, including 
computing capabilities that are not yet available but are expected 
soon. Appropriate attention should be paid to attributes such as 
modularity, interoperability, and scalability.

Program Funding

    Up to $15 million is available in FY 2002, contingent upon 
availability of appropriated funds. It is anticipated that individual 
research grants will be funded at a level of $1-4 million per year. 
Applications should also describe a scientifically justified scale-up 
plan to maximize technology development and research productivity.

Merit and Relevance Review

    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.
    In addition, applications will be evaluated for the robustness of 
their organizational framework and coordination plan.
    The evaluation will include program policy factors such as the 
relevance of the proposed research to the terms of the announcement and 
the Department's programmatic needs. 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.

Applications

    These large, multi investigator applications will be reviewed as 
individual research projects consisting of several individual 
subprojects. The research description (see description of Narrative 
below) for individual subprojects should be no more than 20 pages each, 
exclusive of attachments. The combined research descriptions for all 
individual subprojects for each application should be no more than 100 
pages, exclusive of attachments. In addition, each application should 
contain a project overview, not to exceed 20 pages, that contains an 
overall project summary, research integration plan, management plan, 
data and information management plan, and a communication plan. Each 
research team should identify a single scientific coordinator or point 
of contact for its application.
    Each subproject description 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. Each subproject or project must 
include letters of intent from outside collaborators briefly describing 
the intended contribution of each to the research and short curriculum 
vitaes, consistent with National Institutes of Health (NIH) guidelines, 
for all principal investigators and any co-PIs.
    Information about the development and submission of applications, 
eligibility, limitations, evaluation, selection process, and other 
policies and procedures may be found in the Application Guide for the 
Office of Science Financial Assistance Program and 10 CFR part 605. 
Electronic access to the Guide and required forms is made available via 
the World Wide Web at http://www.science.doe.gov/production/grants/grants.html. DOE is under no obligation to pay for any costs associated 
with the preparation or submission of applications if an award is not 
made.
    The application must contain an abstract or project summary, 
letters of intent from collaborators, and short curriculum vitas 
consistent with NIH guidelines.
    Adherence to type size and line spacing requirements is necessary 
for several reasons. No applicants should have the advantage, or by 
using small type, of providing more text in their applications. Small 
type may also make it difficult for reviewers to read the application. 
Applications must have 1-inch margins at the top, bottom, and on each 
side. Type sizes must be 10 point or larger. Line spacing is at the 
discretion of the applicant but there must be no more than 6 lines per 
vertical inch of text. Pages should be standard 8\1/2\" x 11" (or 
metric A4, i.e., 210 mm x 297 mm).
    Applicants are expected to use the following ordered format to 
prepare Applications in addition to following instructions in the 
Application Guide for the Office of Science Financial Assistance 
Program. Applications must be written in English, with all budgets in 
U.S. dollars.
     Face page (DOE F 4650.2 (10-91))
     Project abstract (no more than one page)
     Budgets for each year and a summary budget page for the 
entire project period (using DOE F 4620.1)
     Budget explanation
     Budgets and budget explanation for each collaborative 
subproject, if any
     Project description (includes goals, background, research 
plan, preliminary studies and progress, and research design and 
methodologies)
     Goals
     Background
     Research plan
     Preliminary studies and progress (if applicable)
     Research design and methodologies
     Literature cited
     Collaborative arrangements (if applicable)
     Biographical sketches (limit 2 pages per senior 
investigator)
     Description of facilities and resources
     Current and pending support for each senior investigator
    The Office of Science, as part of its grant regulations, requires 
at 10 CFR 605.11(b) that a recipient receiving a grant to perform 
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'', 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.
    DOE policy requires that potential applicants adhere to 10 CFR part 
745 ``Protection of Human Subjects'' (if applicable), 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

[[Page 5099]]

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

    Issued in Washington, DC January 28, 2002.
John Rodney Clark,
Associate Director of Science for Resource Management.

[FR Doc. 02-2597 Filed 2-1-02; 8:45 am]
BILLING CODE 6450-02-P