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Notice 01-20 Microbial Cell Project
Department of Energy
Office of Science Financial Assistance Program Notice 01-20; Microbial Cell Project
AGENCY: U. S. Department of Energy (DOE)
ACTION: Notice inviting grant applications
SUMMARY: The Offices of Biological and Environmental Research (OBER), Basic Energy
Sciences (BES), and Advanced Scientific Computing Research (ASCR) of the Office of Science
(SC), U.S. Department of Energy, hereby announce their interest in receiving applications for
research grants in support of the Microbial Cell Project (MCP), an effort to build on information
from completely sequenced microbial genomes to achieve a more comprehensive understanding
of the functioning of a prokaryotic microbial cell. This notice encourages applications from
interdisciplinary scientific partnerships or teams that include such disciplines as microbiology,
molecular biology, applied mathematics, biochemistry, structural and computational biology, as
well as physics, chemistry, engineering and computer science. The MCP is focused on
fundamental research to understand those reactions, pathways, and regulatory networks that are
involved in environmental processes of relevance to the DOE, specifically the bioremediation of
metals and radionuclides, cellulose degradation, carbon sequestration, and the production,
conversion, or conservation of energy (e.g. fuels, chemicals, and chemical feedstocks). Research
areas of particular interest that should be integrated into an interdisciplinary approach can
include studies of: 1) functional analysis of the microbial proteome; 2) biochemical and
physiological characterization; 3) intracellular localization; and 4) cell modeling. This
announcement represents a planned first step in an ambitious effort to understand the functions
of all the macromolecular components in a microbial cell, to understand all their interactions as
they form pathways and processes that are related to DOE-relevant activities, and to eventually
build predictive models for microbial activities that address DOE mission needs.
DATES: Preapplications referencing Program Notice 01-20 should be received by February 21,
2001. Earlier submissions will be gladly accepted. A response to timely preapplications will be
communicated to the applicant by March 9, 2001.
Formal applications in response to this notice should be received by 4:30 p.m., E.D.T., April 24,
2001, to be accepted for merit review and funding in FY 2001.
ADDRESSES: Preapplications referencing Program Notice 01-20 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
encouraged (but not required) for submitting preapplications using the following address:
joanne.corcoran@science.doe.gov.
Formal applications referencing Program Notice 01-20, 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 01-20. 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
Dr. Gregory L. Dilworth, SC-143
The full text of Program Notice 01-20 is available via the World Wide Web using the following
web site address:
http://www.sc.doe.gov/production/grants/grants.html.
SUPPLEMENTARY INFORMATION: The Microbial Cell Project (MCP) supports key DOE
missions by building on the successful DOE Microbial Genome Program that has furnished
microbial DNA sequence information on microbes relevant to environmental remediation, global
carbon sequestration (e.g. CO2 fixation), complex polymer degradation (e.g. cellulose and
lignins), and energy production (fuels, chemicals, and chemical feedstocks). These microbial
genome sequences provide a finite set of “working parts” for a cell; the challenge now is to
understand how these parts are assembled into functional pathways and networks to accomplish
activities of interest to the DOE (specifically those identified in the preceding sentence.) The
traditional reductionist experimental approach has defined specific steps or stages within many
physiological processes; however, the availability of whole genomes affords the opportunity to
integrate these individual pathways into a larger physiological or whole organism framework.
The MCP seeks to integrate available information about individual processes and regulatory
complexes to understand the intracellular environment in which these pathways and networks
exist and function. The DOE Microbial Cell Project is part of a coordinated Federal effort called
the Microbe Project involving elements from several other Federal agencies.
This notice strongly encourages interdisciplinary teams that assemble a range of expertise into an
integrated approach to characterizing the structure and function of a prokaryotic cell. The
purpose of encouraging interdisciplinary teams is to combine diverse scientific talents into a
coordinated program and thus it is very important that a coordination plan describing how the
whole exceeds the sum of the parts be included in the application. In addition, the MCP seeks to
promote research on the internal organization and complex control systems that allow microbial
cells to respond to their environment, to make unique products, and to carry out specialized
functions relevant to DOE missions in the bioremediation of metals and radionuclides, cellulose
degradation, carbon sequestration, and the production, conversion, or conservation of energy.
This effort will exploit a range of approaches, among them: 1) functional analyses of proteins
and protein interactions; 2) metabolic and flux measurements; 3) intracellular imaging
technologies for the localization and quantitation of proteins and other cellular constituents; and
4) computational modeling to represent the activities of a cell in ways that permit testable
predictions of microbial cell functions.
Preference will be given to those applications selecting prokaryotic microbes that satisfy all of
the following criteria: a) the chosen microbe is of DOE mission-relevance, i.e., can bioremediate
metals and radionuclides, sequesters environmental carbon, e.g., can fix CO2, degrades
significant biopolymers such as celluloses and lignins, or generates energy sources, fuels,
chemicals, and chemical feedstocks. Strict pathogens or parasites will not be considered; b)
complete or near-complete genomic sequencing information from the chosen microbe exists in
the public domain; c) the chosen microbe grows sufficiently in culture to enable experimental
work; d) the chosen microbe can easily be genetically transformed; and e) expression vectors are
available. Of particular importance will be a clear description of a coherent plan for making
efficient use of the available sequence information. (See
http://www.ornl.gov/microbialgenomes/organisms.html for a current list of microbes that
have been and are being sequenced.) If a group proposes to carry out work under this notice on a
specific microbe, it should be prepared to justify the merits of the chosen target organism to the
peer review process. It is expected that each project supported by the MCP will be focused on an
energy-related or environmentally relevant microbe (or group of microbes) for which extensive
sequence information is known, although applicants may take advantage of relevant information
derived from other microbes that are not considered DOE targets, e.g. E. coli or yeast. While
integrated and multidisciplinary consortia are strongly encouraged, exceptional applications from
individual investigators focused on more confined aspects or areas may be considered.
This program notice encourages research applications that integrate the following highly
interrelated thrusts, using a single, sequenced, DOE-relevant microbe as the unifying
cornerstone. For the purposes of this notice, the interests of DOE are the bioremediation of
metals and radionuclides, cellulose degradation, carbon sequestration, and energy production,
conversion, or conservation. Integrated applications should include a careful description of how
the project’s proposed interdisciplinary research team will integrate all or most of the following
components into a single research project. These components are:
2) Biochemical and Physiological Characterization. The MCP seeks to go beyond identifying
discrete genes and proteins that participate in a few isolated enzymatic reactions; the interest
is in defining the global interactions among multiple cellular components. How do these
proteins, metabolites, or cellular biomolecules interact with each other to form functional
networks or linkages between the constituents of traditionally described modular pathways?
There is an acute need to know more about the quantitative intracellular physiology and
biochemistry of a microbial cell’s constituents, e.g., assembly dynamics, kinetics, and fluxes
of relevant proteins and cytoplasmic components under in vivo conditions. Applications may
include the use of new high-throughput technologies/tools to better quantify protein
biochemistry inside a cell in response to different conditions and to better understand
regulatory molecules and noncoding regulatory sequences that affect pathways relevant to
the DOE. Of particular interest, are explorations of the physical mechanisms of intracellular
communication and information exchange that underlie the DOE mission relevant processes
listed earlier in this notice. This notice does not encourage research applications directed toward
microarray or “gene-chip” development or construction; however, such arrays or chips may be
used to address the aims of this notice.
3) Intracellular Localization. A microbial cell is not a simple “bag of dilute saline” in which
proteins freely diffuse and interact in ways solely governed by simple diffusion. Although
this assumption (of simplicity) has proven useful in studying protein biochemistry and
reaction kinetics at the level of single enzymes, it does not represent the internal reality of
even a simple microbial cell. This notice encourages research on the intracellular physico-
chemical environment, including the intracellular distribution, localization, movement,
temporal variations, and topological or mechanical constraints on physiological function of
microbial proteins involved in reaction pathways and networks that are of interest to DOE.
Technologies for imaging microbial cell constituents in real time are also of interest.
4) Cell Modeling. It is not presently possible to model every single interaction in a cell, much
less represent its overlapping but distinct networks and pathways in sufficient detail to
capture most its complexity. This notice encourages research applications to develop and
explore computational models of those networks and pathways of interest to the DOE.
Computational models are sought to simulate the intracellular environment at different levels
of resolution: a) at medium resolution, i.e., modeling most of a cell’s proteome, to generate a
rough or approximate predictive understanding of the “minimal metabolic scaffold” for
processes such as methanogenesis, photosynthesis, or metal reduction, or b) at higher
resolution: i.e. for a detailed quantitative representation of a relevant physiological process to
optimize or manipulate a particular reaction, and to accurately predict responses to
environmental perturbations. It is important that any proposed software development
activities be based on modular design, which enables upgrades and expansions to the
predictive modeling capability as more quantitative data about protein biochemistry,
physiology, and intracellular topology becomes available. Of particular importance is that
modeling efforts not be conducted in isolation from the biological “reality” derived from
experimental research. Of special interest will be computational models that would
effectively utilize investments made by the Office of Science in massively parallel, high-
performance computing hardware and software libraries. 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 that some level of user support will be available. Applicants with
an interest in this thrust area are strongly encouraged to explore the companion Program
Notice 01-21, Advanced Modeling and Simulation of Biological Systems, which encourages
the submission of research applications that emphasize the applied mathematics and
computer science advances needed to provide the computational modeling foundation upon
which this notice is focused.
Potential applicants are strongly encouraged to submit a brief preapplication that consists of two
to three pages of narrative describing the research objectives, the technical approach(s), and the
proposed team members and their expertise. The intent in requesting a preapplication is to save
the time and effort of applicants in preparing and submitting a formal project application that
may be inappropriate for the program. Preapplications will be reviewed relative to the scope and
research needs of the Microbial Cell Project, 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. No budget information or biographical data need be included, nor is an institutional
endorsement necessary. A response to timely preapplications will be communicated to the
Principal Investigator by March 9, 2001.
Program Funding
It is anticipated that up to $6 million will be available for all MCP awards in Fiscal Year 2001. It
is anticipated that at least 4 awards will be made to interdisciplinary scientific teams, contingent
on satisfactory peer review, the availability of funds, and the size of the awards. Multiple year
funding is expected, also contingent on availability of funds and progress of the research;
pending the availability of future funding, it is anticipated that this initiative will reflect a long
term commitment to understanding the workings of a microbial cell. Awards to interdisciplinary
teams are expected to range from $0.5 million to $1.5 million per year, total costs, with terms of
one to three years. (A number of awards in the $100 – 200 thousand range, total annual costs,
may be made to exceptional individual investigator applications). The DOE is under no
obligation to pay for any costs associated with the preparation or submission of an application.
DOE reserves the right to fund, in whole or in part, any, all, or none of the applications submitted
in response to this Notice. Applications received by the Office of Science under its normal
competitive application mechanisms may also be deemed appropriate for consideration under
this announcement and may be funded under this program.
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):
Submission Information
The Project Description must be 25 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" (if applicable), 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:
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
The Catalog of Federal Domestic Assistance Number for this program is 81.049, and the
solicitation control number is ERFAP 10 CFR Part 605.
John Rodney Clark
Published in the Federal Register January 23, 2001, Volume 66, Number 15, Pages 7475-7478.
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