[Federal Register Volume 67, Number 221 (Friday, November 15, 2002)]
[Notices]
[Pages 69208-69214]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-29022]
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DEPARTMENT OF ENERGY
Office of Science Financial Assistance Program Notice 03-05:
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 in the
following areas that support the Genomes to Life research program
(http://www.doegenomestolife.org/):
(1) Technologies and strategies to image individual proteins and
multi-protein complexes in microbes and to image complex microbial
communities;
(2) Technologies for the high-throughput synthesis of proteins and
their biological characterization;
(3) Molecular tags to identify individual proteins and to
characterize multi-protein complexes in microbial cells;
(4) High resolution, quantitative microbial biochemistry;
(5) New genomic strategies and technologies for studying complex
microbial communities;
(6) Pathway inference in prokaryotes;
(7) Implications for society, the law, education, and technology
transfer; and
(8) Other novel and innovative technologies and research strategies
to address the core goals of the Genomes to Life research program.
DATES: Statements of intent to apply, including information on
collaborators, areas of proposed research and technology development,
and a short (one page) summary of the proposed research should be
submitted by Tuesday, January 7, 2003.
Formal research applications are due by 4:30 PM E.D.T., Tuesday,
April 22, 2003.
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. Gary
Johnson at: [email protected].
Formal applications in response to this solicitation are to be
electronically submitted by an authorized institutional business
official through DOE's Industry Interactive Procurement System (IIPS)
at: http://e-center.doe.gov/. IIPS provides for the posting of
solicitations and receipt of applications in a paperless environment
via the Internet. In order to submit applications through IIPS your
business official will need to register at the IIPS website. The Office
of Science will include attachments as part of this notice that provide
the appropriate forms in PDF fillable format that are to be submitted
through IIPS. Color images should be submitted in IIPS as a separate
file in PDF format and identified as such. These images should be kept
to a minimum due to the limitations of reproducing them. They should be
numbered and referred to in the body of the technical scientific
application as Color image 1, Color image 2, etc. Questions regarding
the operation of IIPS may be e-mailed to the IIPS Help Desk at:
center.doe.gov">HelpDesk@e-center.doe.gov or you may call the help desk at: (800) 683-
0751. Further information on the use of IIPS by the Office of Science
is available at: http://www.science.doe.gov/production/grants/grants.html.
If you are unable to submit an application through IIPS please
contact
[[Page 69209]]
the Grants and Contracts Division, Office of Science at: (301) 903-5212
in order to gain assistance for submission through IIPS or to receive
special approval and instructions on how to submit printed
applications.
FOR FURTHER INFORMATION CONTACT: Dr. David Thomassen, telephone: (301)
903-9817, e-mail: [email protected], Office of Biological
and Environmental Research, SC-72/Germantown Building; U.S. Department
of Energy; 1000 Independence Avenue, SW.; Washington, DC 20585-1290.
A complementary request for proposals from DOE national
laboratories has been issued, Program Solicitation LAB 03-05.
SUPPLEMENTARY INFORMATION: Biology has entered a new era--the era of
systems biology--in which we will understand entire living organisms
and their interactions with the environment. While scientists have long
tried to understand the workings of individual genes or small groups of
genes this new era in biology will focus research on entire networks of
genes and even entire biological systems--small, single celled
organisms at first and later more complex creatures ultimately
including humans.
This dramatic advance is possible, in large part, because of the
scientific and technical successes of the Human Genome Project. The
information and technology now available to all scientists on the human
genome and on a rapidly growing list of the genomes of other organisms
from microbes to plants to worms to mice not only gives us new
perspectives on the inner workings of biological systems but provides
new opportunities to use this knowledge to solve problems in energy.
The Genomes to Life program is a systems biology research program
that offers the possibility of biotechnology solutions that can give us
abundant sources of clean energy yet control greenhouse gases like
carbon dioxide, a key factor in global climate change, and that can
help us clean up past contamination of the environment.
The overall goals of the Genomes to Life program include
understanding:
1. Natural, multi-protein molecular machines of complex living
systems.
2. Complex networks that control the assembly and operation of
these machines.
3. The organization and biochemical capabilities of complex
microbial communities.
These three goals will only be achieved if we develop:
4. A computational infrastructure for systems biology that enables
the development of computational models for complex biological systems
that can predict the behavior of these complex systems and their
responses to the environment.
The Genomes to Life program supports a combination of large, well
integrated, multidisciplinary research teams and smaller, focused
research projects. This solicitation will support smaller, focused
research projects to develop new technologies, research strategies, or
research resources needed by the Genomes to Life program. Future
solicitations will likely request applications for both large, well
integrated, multidisciplinary research teams and smaller, focused
research projects.
Information on the research projects currently funded by the
Genomes to Life program and a description of project goals and overall
program organization can be found at: http://www.doegenomestolife.org/.
Other useful Web sites include:
Microbial Genome Program Home Page--http://www.sc.doe.gov/ober/microbial.html.
DOE Joint Genome Institute Microbial Web Page--http://www.jgi.doe.gov/JGI_microbial/html/.
Microbes of Interest to DOE. The initial focus of Genomes to Life
is on microbes (including fungi) directly relevant to DOE mission needs
in energy (cleaner energy, biomass conversion, carbon sequestration) or
the environment (cleanup of metals and radionuclides at DOE sites).
Research in Goals 1 and 2 takes advantage of and focuses on microbes
whose complete DNA sequence is already known. Research in Goal 3
focuses on microbes or microbial communities of interest to, directly
relevant to, or that will contribute substantially to an ability to
address DOE mission needs. Selected, well-justified research using
yeast is appropriate as a means of quickly generating data that
addresses the needs of the Genomes to Life Program. However, the use of
yeast as a long-term research focus will not be encouraged.
Data and Other Results. Any data and results 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 or appropriate. 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).
Software Development and Distribution. Software developed by
research teams that is appropriate for distribution beyond the research
team shall be made available to the biological and computational
community. It is our intent that this software be accessible, useful,
affordable, and interoperable with other software and with data.
Applications should include plans for assuring availability, stating
whether: the software will be available as binary or source code, a fee
will be charged for the use of the software, some users (e.g.,
commercial) will be charged while others not, in what way derivative
products will be treated, etc. Statements such as that by the
International Society for Computational Biology on Bioinformatics
Software Availability, http://www.iscb.org/pr.shtml, may be used for
reference.
Research Focus
(1) Technologies and Strategies to Image Individual Proteins and Multi
Protein Complexes in Microbes and to Image Complex Microbial
Communities
This solicitation will promote the development of imaging
technology (probes, instrumentation and computational methodology)
needed to accomplish the Genomes to Life program goals. Applications or
development of imaging technology should be directed to or easily
adapted to the study of microbes. Development of probes and
instrumentation should be complementary to and facilitate completion of
Genomes to Life program goals, including currently funded projects (see
currently funded projects at: http://www.doegenomestolife.org/).
Additional information on the projected imaging needs of the
Genomes to Life program can be found at: http://www.doegenomestolife.org/technology/imaging/GTLimaging2002.pdf.
Specific research needs include:
[sbull] Development of novel probes (fluorescent, electron dense,
vibrational tags, etc.) with optimum physico-chemical properties that
enable:
--Visualization, tracking, assembly and disassembly of multi-protein
molecular machines and their individual components. Multifunctional
probes that measure structure, including post-translational
modification and function in real time, are needed.
--Rapid visualization and quantitation of intracellular processes with
high spatial resolution.
--Visualization and quantitation of microbial populations and
communities with respect to their structure, functions, stability and
response to environmental stress.
[[Page 69210]]
Probes should be developed to determine the spatial and temporal
concentration of nutrients, metabolites, signaling molecules, elements,
extra cellular matrices and other biomolecules critical to maintaining
microbial community structure and function. This should also include
dynamic measuring of oxidative states and energy transfer kinetics.
Probes should be selective, non-perturbative, and resistant to
degradation and should have unique spectroscopic signatures.
Unambiguous experimental systems to validate probe performance should
be presented.
[sbull] Development of new high-throughput tagging methods for
chromophores, electron dense and other probes. Methods should be
capable of being transported to the broader scientific community.
[sbull] Development of innovative optical and non-optical
instrumentation that will visualize and quantitate dynamic aspects of
molecular machines over a wide range of dimensions and time scales;
enable simultaneous co-localization of different intra-cellular
processes with high spatial resolution; and/or permit visualization of
bacterial community composition and functions in the field as well as
in the laboratory.
[sbull] Development of computational methods for rapid processing,
storing, reconstructing, and three dimensional modeling of large image
data sets, e.g., from cryoelectron microscopy. Computational methods
are needed that can predict capabilities and limitations of various
probes and instruments over a wide range of size and time scales. Novel
computational tools are needed to integrate cellular image data sets
derived from different instruments and technologies. Models of
bacterial community structure, growth, functions and adaptive responses
should be constructed based on experimental data and should facilitate
development of alternative experimental approaches.
(2) Technologies for the High-Throughput Synthesis of Proteins and
Their Biophysical Characterization
This solicitation seeks to promote the development of techniques
and protocols for high-throughput, low-cost synthesis of full-length
proteins directly from coding sequence and for their subsequent
biophysical characterization. Availability of proteins will enable the
production and confirmation of selective, non-perterbutive probes and
molecular tags needed to address the broad goals of the Genomes to Life
program.
An essential early requirement for turning genome information into
biological understanding is having access to purified samples of at
least the majority of the proteins encoded in the genomes of interest.
Even within the microbial-focus of Genomes to Life, this requirement is
daunting. It must encompass, within the next decade, hundreds of
different microbes and therefore many tens of thousands of proteins.
Both the production and characterization goals are significantly
broader than those of structural genomics programs. In those programs
the goals are limited to the structural characterization of a
relatively small fraction of proteins, and often protein fragments,
that represent structurally novel motifs.
It is recognized that no satisfactory general approach currently
exists and that not all proteins will likely yield to the same
techniques. It is expected that a variety of both cell-free and cell-
based systems will be required, as well as multiple characterization
methods. Production and characterization technologies should be
scalable, economic, and sufficiently robust to meet the production goal
of milligram quantities of approximately 10,000 proteins per year.
An essential early need is the development of improved techniques
for predicting from sequence what production and purification
approaches are most likely to succeed with each protein. Thus,
informatics is an integral component. Algorithms based on data from
successful and failed protein expressions are expected to substantially
inform and improve future protein production efficiency.
Informatics coupled with biophysical characterizations are expected
to provide functional insights that may also explain why such a large
number of biologically important, full-length proteins either can not
be expressed in soluble form, or have whose structures that cannot be
determined once expressed. These proteins may include substantial
disordered regions that adopt structures only after interaction with
appropriate protein binding partners. Reliable predictive algorithms
based on expression and characterization databases are therefore needed
to predict disorder and binding partners.
Areas in which improvements are sought include:
[sbull] Optimization of cloning and clone validation techniques to
support the protein production process.
[sbull] Optimization of cell-free and cellular expression methods.
[sbull] Optimization of protein purification protocols.
[sbull] Improved strategies for increasing the fraction of proteins
that can be synthesized by automated methods. This may include
sequence-based predictions of methods most likely to succeed and
insights for optimization of expression protocols.
High-throughput, economical approaches for characterizing
synthesized protein to assess product quality and to predict protein
function are also solicited. A goal is to provide multiple benchmark
biophysical characterizations for each protein under several
conditions. These approaches are expected to include:
[sbull] Biophysical techniques, e.g., mass spectrometry circular
dichroism, calorimetry, partial proteolysis, deuterium exchange,
surface plasmon resonance, neutron scattering, nuclear magnetic
resonance.
[sbull] Improved techniques for predicting, from protein sequence,
ordered and dis-ordered domains and for predicting solubility
properties of proteins and protein domains.
[sbull] Integrated data acquisition and management tools for
tracking all steps of the production and characterization process and
for supporting detailed QC/QA procedures.
[sbull] Improved high-throughput methods to predict, then rapidly
test, and finally to confirm binding partners for proteins so that the
nearly infinite number of potential interactions is reduced to
experimentally testable subset.
(3) Molecular Tags To Identify Individual Proteins and To Characterize
Multi-Protein Complexes in Microbial Cells
This solicitation seeks advances in technology needed to mass-
produce molecular tags for proteins and protein complexes, as tools to
be used for determining function. As a top priority, technologies are
sought for mass-producing specific protein recognition tags capable of
functioning as:
[sbull] Capture reagents in affinity extraction and purification
protocols, and as.
[sbull] Labeling reagents for intracellular and `in situ'
localization and mapping studies.
These technologies must be scalable to permit tens of thousands of
successful tags to be produced and characterized per year at affordable
costs. It is recognized that none of the many approaches under
development to address this problem have yet demonstrated compelling
promise--even as generally effective laboratory-scale methods. Yet for
the purposes of
[[Page 69211]]
Genomes to Life and for modern biology altogether, very high-
throughput, industrially robust methods to address this problem are
required.
For the purposes of this solicitation, it is assumed that purified
protein `targets' will be provided to the researchers in micro-gram to
milli-gram quantities so that tags can be optimized and characterized.
Tags that interfere with function as well as those that do not
interfere with protein function are both needed to help better define
the biological roles of proteins. Areas in which technological
improvements are sought include:
[sbull] Scalable methods for producing `epitope-directed' affinity
reagents of high specificity and affinity for proteins capable of
functioning either as affinity extraction and capture reagents or as
intra-cellular labeling reagents. High success ratios (fraction of
protein epitopes yielding useful reagents) are essential.
[sbull] Improvements in protein-directed affinity tag design to
improve tag utility, e.g., to facilitate subsequent purification and
or/imaging, to facilitate release of the tagged protein, to image with
and without disrupting activity, etc.
[sbull] Improved methods for developing tags directed specifically
to protein complexes as distinct from their component proteins.
Labeling complexes with and without disrupting interactions amongst
protein components will provide important functional insights.
[sbull] Improved strategies for predicting, from sequence data,
what potential protein epitopes are likely to be successful targets for
tagging with and without interfering with function, and for predicting
what tag development methods are likely to work for a particular
protein/epitope.
[sbull] Imaging and labeling methods for multiplex mapping of
proteins within cells. Simultaneously monitoring multiple labeled
proteins will provide more comprehensive views of multi-protein
complexes and their activities.
[sbull] Informatics tools both for managing tag production
processes and for managing the data resulting from their use.
(4) High Resolution, Quantitative Microbial Biochemistry
As noted above, the initial focus of Genomes to Life is on microbes
(including fungi) directly relevant to DOE mission needs in energy
(cleaner energy, biomass conversion, carbon sequestration) or the
environment (cleanup of metals and radionuclides at DOE sites). To this
end, development of novel technologies are encouraged to support the
characterization of the internal environment and organization of
prokaryotic microbes relevant to DOE missions and the Genomes to Life
program and to explore how the characteristics of a microbe's internal
environment affect its metabolism and physiology.
Very little is known of the internal ``milieu'' of any cell. A
microbial cell is not likely to be a ``bag of dilute salt water''
within which metabolites and gene products freely diffuse. There is
internal organization due to structural cytoskeletal components,
partitioning of gene products in different parts of the cell so that
they can efficiently mediate their appropriate pathways, concentration
gradients of proteins and small molecules across the volume of the
cell, and physical effects caused by the cell membrane and
intracellular constituents including the viscosity of a cell's
cytoplasm.
A protein's localization within a cell, its relationships with
other proteins, concentrations, and subcellular dynamics are critically
important parameters in determining its function, for identifying
functional networks of proteins in a morphological context, and for
expanding our understanding of whole-cell function. Thus, studies on
the topological, physical, and chemical properties of cellular
cytoplasm, their effects on protein dynamics, on flux rates of
metabolites, on protein-protein and protein-ligand interactions, and
ultimately, on protein function are needed.
Research is needed that furnishes information on the dynamic
behavior of these various molecules as the ``molecular machines''
perform their functions and on the distribution, localization,
movement, and temporal variations of the molecules and complexes inside
individual microbes as they carry out reactions of relevance to DOE
missions and the Genomes to Life Program. Research is also needed to
characterize topological, physical, and chemical characteristics
underlying cellular responses to external stimuli, e.g., nutrients,
toxins, or changes in environmental conditions. Similarly,
computational algorithms designed to recognize regulatory networks or
patterns of gene expression under different circumstances are needed
that can provide insights into co-regulated genes.
New methods that accomplish any of several aims are solicited:
[sbull] Techniques to map the spatial distribution and
concentrations of proteins and metabolites within prokaryotes.
[sbull] Techniques to assess fluxes and changes in concentrations
of metabolites as a function of intracellular parameters and spatial
location.
[sbull] Techniques to effectively map the immediate environment
surrounding specific proteins, protein complexes, or other structural
components within prokaryotes.
[sbull] Techniques to measure changes in enzyme-catalyzed reaction
rates (catabolic and anabolic) and fluxes, as a function of the
internal cell milieu, e.g., distance from the inner membrane surface,
proton concentration, temperature, etc.
[sbull] Techniques to quantitate intracellular protein-protein
association/dissociation rates as a function of ion concentrations,
dielectric constants, protein concentrations, small molecule
(metabolite, cofactor, ligand, etc.) concentrations, or temperature.
[sbull] Techniques to link data from experiments addressing the
above aims to the broader goals of the Genomes to Life Program.
[sbull] Techniques to exploit computational methods to interrogate
resulting datasets in order to suggest experimental priorities and
derive insights into the underlying biology.
(5) New Genomic Strategies and Technologies for Studying Complex
Microbial Communities
Microorganisms are the largest reservoir of genetic and biochemical
diversity on earth. New methods for examining microbial communities
have revealed that uncultured microbes make up more than 99% of many
natural microbial communities. DNA isolated directly from environmental
samples is a tremendous resource for examining the structure and
function of microbial communities. The science of microbial ecology
will be advanced by understanding the distribution, diversity, relative
abundance, and interactions of the microorganisms in these communities.
A goal of the Genomes to Life Program (Goal 3) is to dramatically
extend current scientific and technical understanding of the genetic
diversity and metabolic capabilities of microbial communities in the
environment, especially those related to remediation, biogeochemical
cycles, climate changes, energy production, and biotechnology. A
challenge to achieving this objective, however, is the difficulty in
characterizing the complexity of microbial communities in nature. For
example, it has been estimated that there may be thousands of different
species in surface soils. Thus, new
[[Page 69212]]
strategies and technologies are needed to help define and assess the
repertoire of metabolic capabilities as embodied in the collective
community's genomic sequence.
We need new technologies that enable us to:
[sbull] Determine whole-genome sequences of dominant uncultured
microorganisms to estimate their genetic diversity and
interrelationships. Novel technologies and strategies are needed to use
the genome sequence to identify the genes, metabolic pathways,
regulatory network and proteins needed for survival, growth and
adaptation to the environment.
[sbull] Identify the extent, patterns and spatial distribution of
genetic diversity in microbial communities of interest to the DOE
mission areas. In particular, we need to understand how microbial
diversity supports community structure and function, and the
relationship of genetic diversity to key environmental parameters. For
example, one strategy for understanding the extent and pattern of
genetic diversity in microbial communities is to sequence bacterial
artificial chromosome (BAC) clones from individual microbial
communities by the shotgun approach. Comparing BAC clone sequences
should lead to insights into community genetic diversity and metabolic
capacity.
[sbull] Understand the ecological functions of the uncultured
microorganisms. We need to identify the metabolic functions that these
genomes encode and to understand how those functions contribute to the
community's ecological role in the environment. Of particular interest
is the unique role of novel uncultured microorganisms in ecosystems
relevant to DOE's missions in bioremediation, carbon sequestration,
global climate change, energy production, and biotechnology.
[sbull] Determine cellular and biochemical functions of genes
discovered in uncultured community members. This includes determining
the protein complexes unique to uncultured microorganisms in ecosystems
of DOE relevance, and whether their unique characteristics can be used
for protein engineering.
[sbull] Understand the genetic basis of microbial community
functional stability and adaptation in environments important to DOE
missions. We need to understand the relationship between genetic
diversity and microbial community stability. For example, the genetic
basis and factors controlling microbial community stability and
adaptation is of great importance in managing microbial communities to
bioremediate contaminated sites, sequester carbon from the atmosphere,
and contribute to sustainable energy production.
Key technologies needed to achieve these goals include, but are not
limited to:
[sbull] New approaches for recovering RNA and high-molecular-weight
DNA from environmental samples.
[sbull] New approaches for isolating single cells of uncultured
microorganisms.
[sbull] New parallel comparative approaches that allow unique
microbial community DNA fragments to be identified and the community to
be characterized in automated high-throughput ways.
[sbull] Novel technologies and approaches for defining the patterns
of expression and functions of genes from microbial communities with
large numbers of uncultured microorganisms, under different
environmental conditions.
[sbull] Advanced methods for community genome sequence assembly,
genome comparison, microarray data analysis, and data management.
In addition, there are many computational challenges to
characterizing the composition and functional capabilities of microbial
communities. New algorithms for DNA sequence assembly and annotation
will be required to analyze the multiorganism sequence data, and new
modeling methods will be required to predict the behavior of microbial
communities. Computational methods needed include the ability to
deconvolute mixtures of partial genomes sampled in the environment and
to identify individual organisms; to facilitate multiple-organism
shotgun-sequence assembly; to improve comparative approaches to
microbial sequence annotation and gene finding; to reconstruct pathways
from sequenced or partially sequenced genomes; and to evaluate the
combined metabolic capabilities of heterogeneous microbial populations.
Importantly, computational methods are needed to correlate genomic,
physiological, and biogeochemical site parameters, as well as their
spatial and temporal distribution. Finally, methods to integrate
regulatory-network, pathway, and expression data into integrated models
of microbial community function are needed.
(6) Pathway Inference in Prokaryotes
Many of the future solutions to the problems of supplying energy
without net greenhouse gas emissions, managing the atmosphere's carbon
budget, and remediating environmental contamination from metals,
radionuclides, and toxic chemicals, will be based on biotechnology.
Most of the new biotechnologies will almost certainly arise from
fundamental advances in our understanding the ``microbial world''. This
is primarily due to two facts. First, the metabolism of naturally
occurring microorganisms plays a major role, often a dominant one, in
many of the key chemical and energy fluxes of the planet. Second,
virtually all of the biochemical transformations needed for safe energy
production, carbon management, and environmental cleanup are part of
the natural repertoire of one or more microorganisms. The challenge
therefore is to explore and understand the immense chemical processing
power that the microbial world possesses and uses. Achieving the needed
understanding will require a nearly complete predictive mastery of the
microbial cell from a `systems' point of view--including their
metabolic and signaling pathways, their regulatory networks, their
material and energy flow constraints, etc. Data sets of considerable
size and complexity must be obtained, managed, and mined. In addition,
entirely new realms of modeling and simulation must be mastered.
The research requested in this section builds on advances in both
computation and data base management as well as the extraordinary
increase in the speed and capacity--and a corresponding reduction in
the cost--of genome sequencing. Most fundamentally, it builds on the
new and massive investment in the systems-level genomic-style study of
microbial cells and microbial communities being undertaken as part of
the Genomes to Life initiative.
The research requested in this section will facilitate the use of
data obtained from the genomic and `systems-level' experimental study
of microbes (primarily prokaryotes) and microbial communities. It will
in particular assist in using these data to predict the role played by
each of the proteins encoded in the microbe's genome, the microbe's
signaling and metabolic pathways, its regulatory mechanisms, and its
biochemical capacities. This research will help enable the re-
annotation of incorrectly annotated genomes, the prediction of
functions for unknown genes, and discovery of known functions for which
no genes have been identified. Biochemical capacities with direct
relevance to DOE missions, such as energy production, carbon fixation,
bioremediation, etc. are of particular interest.
Pathway Inference: Information on regulatory, metabolic, and
signaling
[[Page 69213]]
pathways in prokaryotes is growing rapidly. Just as the use of
similarity searches, such as Basic Local Alignment Search Tool, across
genomes of multiple organisms has provided extraordinarily useful
information regarding the imputed function of the target gene
sequences, the research requested in this section is intended to
facilitate similar inferences through probes of pathways in other
organisms, primarily microbes. Although, some new knowledge may be
required experimentally, the emphasis is on providing a computational
infrastructure for this homology searching. Investigators may propose
the construction of specific databases, research on knowledge
representation, and/or tools to measure similarity or provide
inference. Any proposed databases should contain references to the
source of the data, including measures of presumed accuracy, based
partly on whether annotations were derived from experimental results or
computational analogy. Research may be proposed on data structures and
data access tools for the integrative storage of pathway, signaling,
and regulation information needed to support `knowledge' extraction and
in particular the computation of inferences about pathway structure and
function. This goal presents questions concerning the types of data
that should be stored and how they are to be interrelated, queried,
presented, etc. Research also may be proposed to develop tools and
resources that will support computational methods for inferring the
existence and function of signaling, regulatory, and metabolic
pathways. The research in this element initially may be conducted on
organisms chosen for their utility to the research rather than for
their importance to DOE, but the proposed research should show that it
will be transferable to prokaryotes and pathways of DOE interest.
(7) Implications for Society, the Law, Education, and Technology
Transfer
Scientific research takes place in a context of ongoing societal
concerns and expectations. Headlines about DNA, genes, and the new
powers of science to analyze and manipulate fundamental elements of
life vie for our attention daily. The dazzling diversity of
applications of DNA science to fields ranging from medicine and
agriculture to forensics and environmental restoration are having and
will continue to have profound impacts on society and the lives of our
citizenry. Many recent discoveries stem from data and tools generated
by the Human Genome Project, whose goal is to describe in intricate
detail the DNA from humans and other selected organisms by 2003. DNA is
the information molecule that carries instructions for creating and
maintaining all life. Resources and analytical technologies generated
by the Human Genome Project and other genetic research can be applied
to the DNA of all other organisms including those that are currently
centerpieces of Genomes to Life research. Thus, it is important for the
Genomes to Life program to address some of the ethical, legal, and
social issues that may arise from the project.
The Genomes to Life program initially focuses on nonpathogenic
microbes of environmental importance and those that have potential to
address DOE missions such as bioremediation, energy production, global
climate change processes and biotechnology. To this end, research is
solicited into the Implications for Society, the Law, Education, and
Technology Transfer from the research being conducted under the Genomes
to Life program. Investigations are encouraged that focus on:
[sbull] Defining the range, nature and scope of issues raised by
Genomes to Life research or the applications of that research;
[sbull] Exploring legal issues such as intellectual property
protection and commercialization practices that may be relevant to
advances in the Genomes to Life program;
[sbull] Exploring potential economic sequelae to the introduction
of Genomes to Life scientific developments into the marketplace, e.g.,
impacts on the biotechnology sector and other industries;
[sbull] Educational challenges from the Genomes to Life mediated
``paradigm shift'' from reductionist science to a more
``reconstructionist'' science, e.g., the need to present science as
more of a synthetic activity requiring insights from different
scientific disciplines.
The scope of research on the Implications for Society, the Law,
Economics and Education is a work in progress and emphases will evolve
as opportunities are identified to explore the consequences of Genomes
to Life science for society.
(8) Other Novel and Innovative Technologies and Research Strategies To
Address the Core Goals of the Genomes to Life Research Program
Many different technologies, research strategies, and data
resources will be required to successfully address the core goals of
the Genomes to Life program. Applications will be accepted that propose
to develop additional tools, research strategies, or resources that
will help speed success in reaching the core goals of the Genomes to
Life program. In most cases, these new technologies and research
strategies should be scalable and automatable for genome-scale
analyses. A strategy for or demonstration of scalability and
automatability should be described. The relevance to Genomes to Life
goals should be clearly described.
Program Funding
Up to $10 million is available in Fiscal Year 2003, contingent upon
availability of appropriated funds. It is anticipated that individual
research grants will be funded at a level of $250,000 to $1,000,000 per
year.
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.
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
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.
[[Page 69214]]
The application must contain an abstract or project summary,
letters of intent from collaborators, and short curriculum vitas
consistent with NIH guidelines for all Principal and co-Principal
Investigators.
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).
As noted above, color images should be submitted in IIPS as a
separate file in PDF format and identified as such. These images should
be kept to a minimum due to the limitations of reproducing them. They
should be numbered and referred to in the body of the technical
scientific application as Color image 1, Color image 2, etc.
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.
[sbull] Face page (DOE F 4650.2 (10-91))
[sbull] Project abstract (no more than one page) including the name
of the applicant, mailing address, phone, Fax, and e-mail
[sbull] Budgets for each year and a summary budget page for the
entire project period (using DOE F 4620.1)
[sbull] Budget explanation
[sbull] Budgets and budget explanation for each collaborative
subproject, if any
[sbull] Project description (includes goals, background, research
plan, preliminary studies and progress, and research design and
methodologies) not to exceed 20 pages.
--Goals
--Background
--Research plan
--Preliminary studies and progress (if applicable)
--Research design and methodologies
[sbull] Literature cited.
[sbull] Collaborative arrangements (if applicable).
[sbull] Biographical sketches (limit 2 pages per senior
investigator).
[sbull] Description of facilities and resources.
[sbull] 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 81.049, and the solicitation control number is ERFAP 10
CFR part 605.
Issued in Washington, DC, on November 7, 2002.
Ralph H. De Lorenzo,
Acting Associate Director of Science for Resource Management.
[FR Doc. 02-29022 Filed 11-14-02; 8:45 am]
BILLING CODE 6450-01-P