MOLECULAR STRUCTURE/FUNCTION OF ORGANISMS DEGRADING CONTAMINANTS RELEASE DATE: February 3, 2003 RFA: ES–03-005 National Institute of Environmental Health Sciences (NIEHS) ( CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBERS 93.113; 93.115; 95.143 Letter of Intent Receipt Date: March 16, 2003 Application Receipt Date: April 16, 2003 THIS RFA CONTAINS THE FOLLOWING INFORMATION o Purpose of this RFA o Research Objectives o Mechanism(s) of Support o Funds Available o Eligible Institutions o Individuals Eligible to Become Principal Investigators o Special Requirements o Where to Send Inquiries o Letter of Intent o Submitting an Application o Peer Review Process o Review Criteria o Receipt and Review Schedule o Award Criteria o Required Federal Citations PURPOSE OF THIS RFA This RFA is fully titled MOLECULAR ASSESSMENT OF THE STRUCTURE AND FUNCTION OF ECOLOGICAL POPULATIONS IN THE SEQUESTRATION/DEGRADATION OF ENVIRONMENTAL CONTAMINANTS and is within the mission of the National Institute of Environmental Health Sciences (NIEHS) to promote research that will ultimately reduce the burden of human illness and dysfunction from environmental causes. Complementary to this mission are the goals of the national Superfund Program, established by Congress in 1980 to: identify uncontrolled hazardous wastes; characterize the impacts of hazardous waste sites and emergency releases on the surrounding environment (i.e. communities, ecological systems, and ambient air, soil, water); and, institute control or remediation approaches to minimize risk from exposure to these contaminants. In 1986, six years after the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) was enacted, Congress authorized NIEHS to implement a university-based program of basic research and training grants. The intent was to improve the ability to identify, assess, and evaluate the potential health effects of exposure to hazardous waste and to develop innovative chemical, physical and biological technologies for remediating sites contaminated by hazardous substances. The assignment of this Program, the Hazardous Substances Research and Training program [Superfund Basic Research Program (SBRP)], to the NIEHS underscored an emphasis on human health effects assessment, evaluation and prevention. However, NIEHS was provided latitude to support non-traditional NIH research areas such as fate and transport and remediation strategies for environmental contaminants. NIEHS has implemented this program by supporting coordinated multiproject, multidisciplinary university-based programs that link biomedical research with related engineering, hydrogeologic and ecologic research. A component of this multidisciplinary approach has been basic research focused on the mechanistic basis for chemical degradation and sequestration by microbial as well as other biological systems and exploiting this knowledge to develop improved bioremediation strategies for hazardous substances that limit and/or prevent exposure. The research supported by the SBRP has been successful in applying cutting edge molecular research tools to advance our understanding of biological processes involved in the degradation and sequestration of hazardous chemicals ( For example innovative approaches applying microarray technology have been used to begin to understand how microbial populations respond to chemicals in environmental media. This initiative is designed to encourage the research community to apply molecular approaches to assess the structure and function of ecological populations involved in the sequestration and degradation of environmental contaminants. These populations could include microorganisms such as bacteria and fungi, nematodes, aquatic organisms, plants, or any other ecological population that could be used for bioremediation purposes. There have been remarkable advancements in the development of molecular tools over the past few years, and there is an ever-growing use of these molecular approaches to advance bioremediation strategies. However, this is a rapidly evolving area of research. Therefore, it is the intent of this solicitation to support exploratory or developmental research grants in this area. This RFA will make use of the NIH R21 Exploratory/Developmental Research Grant mechanism which is ideally suited to foster the introduction of novel scientific ideas, methods, model systems, tools or technologies that have the potential to substantially advance bioremediation practices. RESEARCH OBJECTIVES Background Contamination of soils, sediments and groundwaters by hazardous substances represents a significant potential threat to human and ecological health. Bioremediation, whether it be in situ, using naturally occurring microorganisms, or attenuated by adding genetically modified organisms such as plants or microbes, holds great promise as a mechanism to convert toxic chemicals to harmless forms. Therefore, bioremediation can be viewed as a preventive medicine of the future, and it will be essential to know the natural habitat of the degradative or sequestrative microbial populations as well as the structure and function of these populations in order to embark on cost effective, ecologically safe and environmentally sound bioremediation plans. The requirement of living systems to both acquire and reject toxic chemicals has led to the selection of a whole repertoire of mechanisms of interactions that ensure the adaptation of microorganisms to a changing and frequently hostile environment. Although microbes that have the capacity to grow on unusual carbon sources or thrive under extreme conditions have been known for several decades, it has only been recently that it has been possible to understand the molecular basis of these specific properties. Genetic analysis of these microbes can suggest new ways to handle toxic pollutants. Although genetic changes develop through natural selection, it takes a long time for an organism to adapt and be capable of cleaning up modern-day pollution. A challenge is to recreate and accelerate these natural processes by using genetic engineering for improving biodegradation of recalcitrant pollutants. The anticipation that genetically engineered organisms would greatly enhance remediation options has not been realized, partly, because the results obtained under controlled laboratory conditions do not readily translate to real world situations. A genetically engineered organism released into a community faces many unknown factors. It must establish itself, interact with other members of the community in unknown ways and face a multitude of poorly controlled external factors. Our ability to understand, monitor and manipulate the complex microbial communities performing bioremediation has been hampered in the past by reliance upon traditional culture-based techniques. One of the existing challenges has been to link changes in population structure with system-level processes where the composition of the community is not known a priori and the function of the individual populations cannot be studied in defined cultures. Our understanding of how microbial or other ecological populations develop an ability to adapt to and transform contaminants is limited because of an inability to predict when adaptive events will occur. Many of these issues of microbial ecology and biodiversity and adaptation now have the potential to be addressed through the use of molecular techniques. For example, DNA chips or gene expression arrays could be used to create a "metagenomic" library that captures the genetic diversity of an entire microbial ecosystem. By applying molecular tools to these various communities not only will it be possible to begin to ascertain the relationship between structure/function and ultimately outcome, but this knowledge can also be used to develop biomarkers of contaminant stress. Many Superfund hazardous waste sites contain a large number of diverse toxic chemicals such as polycyclic aromatic hydrocarbons (PAHs), other chlorinated organics and metals. In addition, many contain synthetic chemicals having novel structures that are rarely found in nature; hence they are degraded slowly by naturally occurring organisms. Through the multidisciplinary nature of the SBRP, both basic and applied research has been supported that has led to the development of innovative bioremediation strategies that are tackling these difficult contamination scenarios. For example, bioremediation strategies have included the use of microbes and engineered microbes, to reduce or eliminate the toxicity of hazardous substances. Phytoremediation strategies are being developed to remove volatile organics and metals from aquifers and sediments. Although progress is being made, our inability to understand at a mechanistic level the relationships between the number and type of species found at a site, the environmental contaminants, the nutrient requirements and other factors that need to be considered in developing efficient bioremediation strategies has hampered the application of innovative bioremediation strategies at complex waste sites. The potential to greatly enhance the effectiveness of bioremediation strategies by applying molecular tools to understand these interactions shows great promise. For example, 16S rRNA-targeted technologies have been used as important tools in molecular microbial ecology to identify, and quantitate microbial populations directly from environmental samples without the need to culture. This methodology has yielded significant information regarding the structure of degradative microbial communities. However, it has not been effective in providing functional information of these target communities. Developing molecular tools that can address both these issues would be a major advance. Objectives and Scope A goal of this proposed research initiative is to stimulate the use of modern molecular biology tools as well as biochemical, cellular or engineering approaches to enhance our understanding of the basic structural and functional properties of ecological populations that are involved in the bioremediation of hazardous substances. The SBRP has provided long-term investments in basic research, with the appreciation that this investment could result in useful applications directed toward attenuation and prevention of exposure. It is expected that the projects supported under this solicitation will enhance the overall goals of the SBRP. The overarching goal of the SBRP is that support of basic research builds the foundation of knowledge necessary to realize practical benefits for the environment and public health, by lowering cleanup costs and improving human and ecological risk assessments. For more information about the SBRP refer to the SBRP website that describes all projects supported by the program: Although the basic research supported by the SBRP has been through large multi-project grants, this solicitation provides an opportunity to address an emerging need by supporting individual research grants that focus on integrating molecular, cellular, biochemical and engineering approaches for structural and functional studies of populations involved in the remediation of hazardous substances. The NIH R21 Exploratory/Developmental Research Grant mechanism will be used. This mechanism is intended to encourage research projects that are distinct from those supported through the traditional R01 mechanism. For example, long-term projects, or projects designed to increase knowledge in a well-established area will not be considered. Applications submitted under this mechanism should be innovative and novel, whether breaking new ground or extending previous discoveries or adapting scientific tools towards new directions or applications. This solicitation is in support of basic developmental/exploratory research that will enhance our ability to understand at a mechanistic level the relationships between the number and type of species found at a site, the environmental contaminants, the nutrient requirements and other factors that need to be considered in developing efficient bioremediation strategies. Genetic engineering of novel organisms to degrade or sequester hazardous chemicals as a project in itself will be considered non-responsive to the RFA. However, genetically engineered organisms being developed and studied within a framework that considers its role within a population of organisms is acceptable within the context of this RFA. Suggested research topics appropriate for this initiative include but are not limited to the following: o Developing novel methods for molecular ecology o Monitoring bioremediation effectiveness by applying molecular tools o Conducting studies designed to understand the impact of chemical contaminants on population diversity at sites o Conducting studies designed to understand the impact of chemical contaminants on the function of populations degrading and or sequestering hazardous substances o Conducting studies to link changes in population structure with system- level effects and the function of the individual populations o Developing and monitoring innovative bioremediation strategies with mixed populations Approaches should take advantage of state-of-the-art molecular, engineering or bioengineering methods that can be applied to better understand the structure and function of ecological populations such as microbes, nematodes, aquatic organisms, plants, etc., that are involved in the degradation or sequestration of hazardous substances found in environmental media such as soil, sediments and aquifers. Appropriate chemicals for bioremediation approaches are: o Hazardous substances found with some frequency at Superfund sites. o Hazardous breakdown products of such substances formed in environmental media. o Mixtures of substances or breakdown products of such substances found with some frequency at Superfund sites. Note also that the applicant may refer to the Web site: to obtain information on hazardous substances that are relevant to Superfund and to the Environmental Protection Agency (EPA) and the Agency for Toxic Substances and Disease Registry (ATSDR). Substances that have been of particular interest to the SBRP include PAHs, polychlorinated hydrocarbons (PCBs), other chlorinated organics and metals. Examples of tools that could be applied in structure/function analysis include but are not limited to the following: o gene expression microarrays o proteomic methodologies o 16-S rRNA-targeted technologies o real-time quantitative polymerase chain reaction (RT-qPCR) o bio-analytical sensors o cell-based bioassays o clone library construction/sequencing o terminal restriction fragment length polymorphisms (T-RFLP) o fluorescent in situ hybridization Note: Studies proposed under this RFA will not support vertebrate animals or human subjects research. MECHANISM OF SUPPORT This RFA will use the NIH R21 Exploratory/Developmental Research grant award mechanism. As an applicant you will be solely responsible for planning, directing, and executing the proposed project. This RFA is a one-time solicitation. The anticipated award date is September 30, 2003. This RFA uses just-in-time concepts. It also uses the modular budgeting format. (see Specifically, if you are submitting an application with direct costs in each year of $250,000 or less, use the modular format. This program does not require cost sharing as defined in the current NIH Grants Policy Statement at FUNDS AVAILABLE The NIEHS intends to commit approximately $1.5 million of SBRP appropriated funds in FY 2003 to support six to eight new grants in response to this RFA. An applicant may request a project period of up to two years. The direct costs for the two-year project period may not exceed $275,000. For example, if you request $150,000 direct costs in year one, the maximum available for direct costs in year two is $125,000. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the NIEHS provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. ELIGIBLE INSTITUTIONS You may submit an application if your institution has any of the following characteristics: o For-profit or non-profit organizations o Public or private institutions, such as universities, colleges, hospitals, and laboratories o Units of State and local governments o Eligible agencies of the Federal government o Domestic or foreign INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs. SPECIAL REQUIREMENTS Annual Meetings: The SBRP holds annual meetings that are hosted by one of the grantee institutions receiving P42 funds. These meetings are multidisciplinary in nature and it is expected that R21 grantees plan to attend the annual SBRP meeting. The annual meeting allows for the exchange of information among investigators. Applicants must budget travel costs for the Principal Investigator to attend. WHERE TO SEND INQUIRIES We encourage inquiries concerning this RFA and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues: o Direct your questions about scientific/research issues to: Claudia Thompson, Ph.D. Scientific Program Administrator Division of Extramural Research and Training National Institute of Environmental Health Sciences P.O. Box 12233, EC-27 79 T.W. Alexander Drive Research Triangle Park, NC 27709 Telephone: 919-541-4638 Fax: 919-541-4937 E-mail: o Direct your questions about peer review issues to: Sally Eckert-Tilotta, Ph.D. Scientific Review Administrator Scientific Review Branch Division of Extramural Research and Training National Institute of Environmental Health Sciences P.O. Box 12233, EC-30 79 T.W. Alexander Drive Research Triangle Park, North Carolina 27709 Telephone: 919-541-1446 Fax: 919-541-2503 E-mail: o Direct your questions about financial or grants management matters to: Ms. Jacqueline Russell Grants Management Officer Grants Management Branch Division of Extramural Research and Training National Institute of Environmental Health Science P.O. Box 12233, EC-22 79 T.W. Alexander Drive Research Triangle Park, NC 27709 Telephone: 919-541-0751 Fax: 919-541-2860 E-mail: LETTER OF INTENT Prospective applicants are asked to submit a letter of intent that includes the following information: o Descriptive title of the proposed research o Name, address, and telephone number of the Principal Investigator o Names of other key personnel o Participating institutions o Number and title of this RFA Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows NIEHS staff to estimate the potential review workload and plan the review. The letter of intent is to be sent by March 16, 2003. The letter of intent should be sent to: Sally Eckert-Tilotta, Ph.D. Scientific Review Administrator Scientific Review Branch Division of Extramural Research and Training National Institute of Environmental Health Sciences P.O. Box 12233, EC-30 79 T. W. Alexander Drive Research Triangle Park, North Carolina 27709 Telephone: 919-541-1446 Fax: 919-541-2503 E-mail: SUBMITTING AN APPLICATION Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001). The PHS 398 is available at in an interactive format. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: SUPPLEMENTAL INSTRUCTIONS o The description (abstract), must include a brief explanation of how the intent of the application is consistent with the exploratory/development nature of the R21 mechanism as described in this notice. o Although preliminary data are neither expected or required for an R21 application, they may be included. o Sections a-d of the Research Plan may not exceed 15 pages, including tables and figures. o Appendix materials should be limited, as is consistent with the exploratory nature of the R21 mechanism, and should not be used to circumvent the page limit for the research plan. Copies of appendix material will only be provided to the primary reviewers of the application and will not be reproduced for wider distribution. The following materials may be included in the appendix: (1) Up to five publications, including manuscripts (submitted or accepted for publication), abstracts, patents, or other printed materials directly relevant to the project. These may be stapled as sets. (2) Surveys, questionnaires, data collection instruments, and clinical protocols. These may be stapled as sets. (3) Original glossy photographs or color images of gels, micrographs, etc., provided that a photocopy (may be reduced in size) is also included within the 15-page limit of items a-d of the research plan. Identify each item with the name of the Principal Investigator. SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications must be submitted in a modular grant format. The modular grant format simplifies the preparation of the budget in these applications by limiting the level of budgetary detail. Applicants request direct costs in $25,000 modules. Section C of the research grant application instructions for the PHS 398 (rev. 5/2001) at includes step-by-step guidance for preparing modular grants. Additional information on modular grants is available at USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001) application form must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of the application, including the Checklist, and three signed, photocopies, in one package to: Center For Scientific Review National Institutes Of Health 6701 Rockledge Drive, Room 1040, MSC 7710 Bethesda, MD 20892-7710 Bethesda, MD 20817 (for express/courier service) At the time of submission, send two additional copies of the application and include five collated sets of all appendix material to: Sally Eckert-Tilotta, Ph.D. Scientific Review Administrator Scientific Review Branch Division of Extramural Research and Training National Institute of Environmental Health Sciences P.O. Box 12233, EC-30 79 T. W. Alexander Drive Research Triangle Park, North Carolina 27709 Telephone: 919-541-1446 Fax: 919-541-2503 E-mail: APPLICATION PROCESSING: Applications must be received on or before the application receipt date of April 16, 2003 as listed in the heading of this RFA. If an application is received after that date, it will be returned to the applicant without review. Although there is no immediate acknowledgment of the receipt of an application, applicants are generally notified of the review and funding assignment within 8 weeks. The Center for Scientific Review (CSR) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an Introduction addressing the previous critique. PEER REVIEW PROCESS Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by the NIEHS. Incomplete and/or non-responsive applications will be returned to the applicant without further consideration. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NIEHS in accordance with the review criteria stated below. As part of the initial merit review, all applications will: o Receive a written critique. o Undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of the applications under review, will be discussed and assigned a priority score. o Receive a second level review by the National Advisory Environmental Health Sciences Council. REVIEW CRITERIA The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments, reviewers will be asked to discuss the following aspects of your application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals: o Significance o Approach o Innovation o Investigator o Environment The scientific review group will address and consider each of these criteria in assigning your application's overall score, weighting them as appropriate for each application. Your application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, you may propose to carry out important work that by its nature is not innovative but is essential to move a field forward. (1) SIGNIFICANCE: Does your study address an important problem? If the aims of your application are achieved, how do they advance scientific knowledge? What will be the effect of these studies on the concepts or methods that drive this field? (2) APPROACH: Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, and appropriate to the aims of the project? Do you acknowledge potential problem areas and consider alternative tactics? (3) INNOVATION: Does your project employ novel concepts, approaches or methods? Are the aims original and innovative? Does your project challenge existing paradigms or develop new methodologies or technologies? (4) INVESTIGATOR: Are you appropriately trained and well suited to carry out this work? Is the work proposed appropriate to your experience level as the principal investigator and to that of other researchers (if any)? (5) ENVIRONMENT: Does the scientific environment in which your work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? For R21 applications, the above stated criteria will be reviewed but it will be noted that the R21 is a developmental/exploratory grant mechanism that is used for projects to generate preliminary data to develop novel hypotheses. Therefore, review standards for preliminary data and past performance are not applicable for this mechanism. ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following items will be considered in the determination of scientific merit and the priority score: o PROTECTIONS: The adequacy of the proposed protection for humans, animals, or the environment, to the extent they may be adversely affected by the project proposed in the application. o DATA SHARING: The adequacy of the proposed plan to share data. o BUDGET: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. RECEIPT AND REVIEW SCHEDULE Letter of Intent Receipt Date: March 16, 2003 Application Receipt Date: April 16, 2003 Peer Review Date: July, 2003 Council Review: September 15-16, 2003 Earliest Anticipated Start Date: September 22, 2003 AWARD CRITERIA Award criteria that will be used to make award decisions include: o Scientific merit (as determined by peer review). o Availability of funds. o Programmatic priorities. REQUIRED FEDERAL CITATIONS PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at Applicants may wish to place data collected under this RFA in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award. URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site. HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This RFA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at AUTHORITY AND REGULATIONS: This program is described in the Catalog of Federal Domestic Assistance at and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

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