PLANNING GRANTS FOR MOLECULAR EPIDEMIOLOGY IN THE ENVIRONMENTAL GENOME PROJECT Release Date: April 20, 2001 RFA: RFA-ES-01-005 National Institute of Environmental Health Sciences (http://www.niehs.nih.gov) Letter of Intent Receipt Date: June 13, 2001 Application Receipt Date: July 13,2001 THIS RFA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. IT INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS RFA. PURPOSE The purpose of this Request for Applications (RFA) is to build collaborations between scientists working in the fields of epidemiology, environmental health sciences, molecular biology, and biostatistics to plan novel and innovative molecular epidemiology studies of environmentally induced diseases. A focus on using high through-put technology in molecular epidemiology studies of environmental response genes is intended, as well as the development of new biostatistical methods to support such studies. This program is seen as integral to the National Institute of Environmental Health Science (NIEHS) Environmental Genome Project (EGP). 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, "Planning Grants for Molecular Epidemiology in the Environmental Genome Project" is related to the priority area of Environmental Health. Potential applicants may obtain a copy of "Healthy People 2010" at http://health.gov/healthypeople/ ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible to apply for R21 exploratory/planning grants but may participate as a subcontractor. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) exploratory/planning grant (R21) award mechanism. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for an application submitted in response to this RFA may not exceed three years. This RFA is a one-time solicitation. The anticipated award date is April, 2002. Specific application instructions have been modified to reflect "MODULAR GRANT" and "JUST-IN-TIME" streamlining efforts being examined by the NIH. Complete and detailed instructions and information on Modular Grant applications can be found at http://grants.nih.gov/grants/funding/modular/modular.htm FUNDS AVAILABLE NIEHS intends to commit approximately $2 million in FY 2002 to fund eight to ten new awards in response to this RFA. An applicant may request a project period of up to three years and a budget for direct costs of up to $150,000 per year. Although the financial plan of NIEHS is to 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 applications of outstanding scientific and technical merit. RESEARCH OBJECTIVES Background An individual’s risk of disease is determined by the complex interplay between genetic susceptibility, environmental exposures and aging. The mission of the NIEHS is to study the interaction of these factors in determining the risk of environmentally induced diseases, such as asthma, birth defects, autoimmune diseases, and cancer. The rapid advances in molecular genetic technologies provide new opportunities to understand the genetic basis for individual differences in susceptibility to environmental exposure. The NIEHS is expanding its research program on genetic susceptibility to environmentally associated diseases through the EGP. This project, which is making use of technology developed by the Human Genome Project, is aimed at the identification of allelic variants (polymorphisms) of environmental disease susceptibility genes in the U.S. population, developing a central database of polymorphisms for these genes, and fostering population-based studies of gene-environment interaction in disease etiology. By identifying those genes and allelic variants that affect individual response to environmental agents, scientists can better predict health risks and assist regulatory agencies in the development of environmental protection policies. While a host of genes that play a role in susceptibility to environmental exposure have been identified, the polymorphisms of these genes have not been systematically sought, identified, or reported. Currently epidemiological studies have focused on a limited number of genes when exploring gene-disease or gene-environment-disease relationships. Very soon thousands of genes will be sequenced and their function elucidated such that the knowledge of their metabolic and physiologic importance will be more complete. More advanced epidemiological and biostatistical methods must be developed to incorporate this information into future molecular epidemiology studies of disease risk. Currently work is underway in two sequencing centers to identify new single nucleotide polymorphisms in genes regulating DNA repair, cell cycle control, and drug metabolizing enzymes. Structure-function relationships of polymorphisms of interest are also being studied as part of the NIEHS Mouse Comparative Genome Centers and at individual research projects supported at universities around the U.S. More information about the EGP, including descriptions of currently funded projects, can be viewed at http://www.niehs.nih.gov/envgenom/home.htm. Research on human populations describing the frequency of these polymorphisms and the support of molecular epidemiologic studies focused on elucidating the associations between genetic variants and environmental exposures are important parts of the EGP. As genetic technology develops, these molecular epidemiologic studies should be designed to incorporate appropriate innovations. Dialog between molecular biologists and environmental epidemiologists at the early stages is key in order to make progress. This RFA is intended to bring together multidisciplinary teams of scientists at institutions or consortiums of institutions to work on issues central to conducting molecular epidemiology studies of environmentally induced diseases such as asthma and other respiratory diseases, birth defects, neurological diseases, and cancer. These teams will include epidemiologists, biostatisticians, ethicists, molecular biologists experienced in using high through-put technologies, and toxicologists and/or other environmental health scientists. Partnerships with the biotechnology industry are encouraged to bring new technological advances in genomic and informatic sciences to the practice of epidemiology. The application for this planning grant should address four areas: (1) overall scientific theme, (2) strategies for crosstalk among the multidisciplinary team, (3) collaborations to integrate novel technologies and/or methodologies into epidemiologic research, and (4) pilot projects or small scale research projects for year 01 and strategies for developing pilot projects in future years. The work of each consortium should be theme related, focusing on issues related to quantifying the risk of environmentally induced diseases associated with specific gene and environmental factors and the interactions of these factors. This program is not meant to provide funds for carrying out the complex field work and analysis of these specific gene-environment interactions, but rather to identify the issues/needs related to carrying out molecular epidemiologic studies and to begin to address them within a multidisciplinary context. Each planning team can begin work on developing the collaborations and intellectual frameworks necessary to conduct future molecular epidemiologic studies as part of the EGP within this program. Plans for educating members of the multidisciplinary teams in the language of each field of science are a critical part of this planning activity. These activities may include seminars, journal clubs, working groups, as well as retreats and may be included in the scope of the proposal. It is intended that the teams will make use of novel technologies in planning for future studies. Due to the small size of these grants, funds should not be used for large purchases of new equipment, but rather could be used towards pay back arrangements for utilizing such equipment at specialized centers of research such as NIEHS Environmental Health Sciences Centers or General Clinical Research Centers. Research funds may be provided for pilot work, feasibility studies, or small scale research projects of a methodological or statistical nature. Pilot projects may be one to three years in duration. Details about these projects should be included in the application. They should be limited to three to four pages each, providing sufficient detail for peer-review, including a short introduction, hypothesis, experimental approach, expected results, and it’s significance to future studies for the Environmental Genome Project. Research conducted under this planning grant may include activities in these broad categories, but is not limited to: o Validation of genotyping and gene expression assays in stored samples using new high through-put technologies. o Determination of frequency distributions of allelic variants (polymorphisms) discovered as part of the EGP in human populations. o Development of new statistical methods and bioinformatics to analyze data generated from high through-put analysis of the human genome in epidemiological studies. o Development of novel study designs to conduct molecular epidemiology as part of the EGP. o Research on innovative study designs necessary to conduct molecular epidemiologic studies as part of the EGP. o Investigation of ethical issues associated with conducting molecular epidemiologic studies as part of the EGP. Some examples of relevant pilot or small scale research activities are designing and field testing novel strategies for collecting and storing blood and DNA specimens, inclusion of gene expression chips methodologies which contain relevant panels of genes and determining response patterns and chemical specific signatures in epidemiologic studies, use of strategies to pool DNA samples to estimate allele frequency, development of new methodologic paradigms to study multi-gene pathways, development of appropriate statistical approaches to handle large amounts of data from microarray or other genomic assays, and focus groups or other activities to assess the feasibility of conducting gene-environment studies in minority, low socioeconomic, or other hard to reach populations. Extensive molecular epidemiologic studies including primary data collection will not be part of this RFA. More comprehensive molecular epidemiologic studies may be supported by future initiatives and/or by regular investigator initiated applications. Work done under this planning grant or similar activities will be considered important preliminary work towards these future studies. SPECIAL REQUIREMENTS It is strongly recommended that each planning team include representative(s) for each of the following disciplines: o Epidemiology o Molecular Biology o Biostatistics/Bioinformatics o Environmental Health Sciences or Toxicology o Ethics It is required that scientists in least three of these disciplines be included in the application. Other disciplines, such as clinical sciences and behavioral/social scientists relevant to the disease under study, may be added to the team if necessary. Representatives from community-based organizations or advocacy groups should be considered as important team members. Grantees will meet together with program staff and other members of NIEHS involved in work relating to the Environmental Genome Project every year of the project period. Grantees should plan for an annual trip to NIEHS in Research Triangle Park, North Carolina for at least two investigators and budget appropriately. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH-supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification are provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43.) All investigators proposing research involving human subjects should read the UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research," published in the NIH Guide for Grants and Contracts on August 2, 2000 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html), a complete copy of the updated Guidelines are available at http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm: The revisions relate to NIH defined Phase III clinical trials and require: a) all applications or proposals and/or protocols to provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable, and b) all investigators to report accrual, and to conduct and report analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of NIH that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. This policy applies to all initial (Type 1) applications submitted for receipt dates after October 1, 1998. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects" that was published in the NIH Guide for Grants and Contracts, March 6, 1998, and is available at the following URL address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html Investigators also may obtain copies of these policies from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. 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. Reviewers are cautioned that their anonymity may be compromised when they directly access an Internet site. LETTER OF INTENT Prospective applicants are asked to submit a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. 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 to: Brenda Weis, Ph.D. Scientific Review Administrator Scientific Review Branch Office of Program Operations Division of Extramural Research and Training National Institute of Environmental Health Sciences P.O. Box 12233, EC-30 111 T.W. Alexander Drive (for express/courier service) Research Triangle Park, NC 27709 Telephone: (919)541-4964 Fax: (919)541-2503 Email: weis@niehs.nih.gov APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 4/98) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/710-0267, email: grantsinfo@nih.gov The modular grant concept establishes specific modules in which direct costs may be requested as well as a maximum level for requested budgets. Only limited budgetary information is required under this approach. The just-in-time concept allows applicants to submit certain information only when there is a possibility for an award. It is anticipated that these changes will reduce the administrative burden for the applicants, reviewers and Institute staff. The research grant application form PHS 398 (rev. 4/98) is to be used in applying for these grants, with the modifications noted below. SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS BUDGET INSTRUCTIONS Modular Grant applications will request direct costs in $25,000 modules, up to a total direct cost request of $150,000 per year. The total direct costs must be requested in accordance with the program guidelines and the modifications made to the standard PHS 398 application instructions described below: PHS 398 o FACE PAGE - Items 7a and 7b should be completed, indicating Direct Costs (in $25,000 increments up to a maximum of $150,000) and Total Costs [Modular Total Direct plus Facilities and Administrative (F&A) costs] for the initial budget period. Items 8a and 8b should be completed indicating the Direct and Total Costs for the entire proposed period of support. o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD - Do not complete Form Page 4 of the PHS 398. It is not required and will not be accepted with the application. o BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT - Do not complete the categorical budget table on Form Page 5 of the PHS 398. It is not required and will not be accepted with the application. o NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant Budget Narrative page. (See URL http://grants.nih.gov/grants/funding/modular/modular.htm for sample pages.) At the top of the page, enter the total direct costs requested for each year. This is not a Form page. o UNDER PERSONNEL - List all project personnel, including their names, percent of effort, and roles on the project. No individual salary information should be provided. However, the applicant should use the NIH appropriation language salary cap and the NIH policy for graduate student compensation in developing the budget request. For Consortium/Contractual costs, provide an estimate of total costs (direct plus facilities and administrative) for each year, each rounded to the nearest $1,000. List the individuals/organizations with whom consortium or contractual arrangements have been made, the percent effort of all personnel, and their role on the project. Indicate whether the collaborating institution is foreign or domestic. The total costs for a consortium/contractual arrangement is included in the overall requested modular direct cost amount. Include the Letter of Intent to establish a consortium. Provide an additional narrative budget justification for any variation in the number of modules requested. o BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used by reviewers in the assessment of each individual"s qualifications for a specific role in the proposed project, as well as to evaluate the overall qualifications of the research team. A biographical sketch is required for all key personnel, following the instructions below. No more than three pages may be used for each person. A sample biographical sketch may be viewed at: http://grants.nih.gov/grants/funding/modular/modular.htm - Complete the educational block at the top of the form page. - List position(s) and any honors. - Provide information, including overall goals and responsibilities, on research projects ongoing or completed during the last three years. - List selected peer-reviewed publications, with full citations. o CHECKLIST - This page should be completed and submitted with the application. If the F&A rate agreement has been established, indicate the type of agreement and the date. All appropriate exclusions must be applied in the calculation of the F&A costs for the initial budget period and all future budget years. o The applicant should provide the name and phone number of the individual to contact concerning fiscal and administrative issues if additional information is necessary following the initial review. The RFA label available in the PHS 398 (rev. 4/98) 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 sample RFA label is available at: http://grants.nih.gov/grants/funding/phs398/label-bk.pdf and has been modified to allow for this change. Please note this is in pdf format. 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, two additional copies of the application must be sent to: Brenda Weis, Ph.D. Scientific Review Administrator Scientific Review Branch Office of Program Operations Division of Extramural Research and Training National Institute of Environmental Health Sciences P.O. Box 12233, EC-30 111 T.W. Alexander Drive (for express/courier service) Research Triangle Park, NC 27709 Telephone: (919)541-4964 Fax: (919)541-2503 Email: weis@niehs.nih.gov Applications must be postmarked by the application receipt date listed in the heading of this RFA. If an application is postmarked after that date, it will be returned to the applicant without review. 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. REVIEW CONSIDERATIONS 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, a process will be used by the initial review group in which applications receive a written critique and 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, assigned a priority score, and 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 the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighing them as appropriate for each application. Note that the 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, an investigator 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 this planning grant address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? (2) Approach: Does the Principal Investigator present a coherent and well designed strategy to enhance crosstalk in order to build a multidisciplinary research program in molecular epidemiology? Are the conceptual framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? (3) Innovation: Does the project employ novel concepts, approaches or methods? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? Do the pilot projects represent unique opportunities for enhancing our ability to integrate human genomic sciences into epidemiologic research? (4) Investigator: Are the required investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the Principal Investigator and other researchers (if any)? (5) Environment: Does the scientific environment in which the 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? In addition to the above criteria, in accordance with NIH policy, all applications will also be reviewed with respect to the following: o The adequacy of plans to include both genders, minorities and their subgroups, and children as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. o The reasonableness of the proposed budget and duration in relation to the proposed research. o The adequacy of the proposed protection for humans or the environment, to the extent they may be adversely affected by the project proposed in the application. The initial review group will also examine the provisions for the protection of human subjects and the safety of the research environment. Schedule Letter of Intent Receipt Date: June 13, 2001 Application Receipt Date: July 13, 2001 Peer Review Date: October, 2001 Council Review: February, 2002 Earliest Anticipated Start Date: April, 2002 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 INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Gwen W. Collman, Ph.D. Scientific Program Administrator Chemical Exposures and Molecular Biology Branch Office of Program Development Division of Extramural Research and Training National Institute of Environmental Health Sciences P.O. Box 12233 111 T. W. Alexander Drive, MD EC-21 Research Triangle Park, NC 27709 Telephone: (919) 541-4980 Fax: (919) 316-4606 Email: collman@niehs.nih.gov Direct inquiries regarding fiscal matters to: Mr. Dwight Dolby Grants Management Specialist Grants Management Branch Office of Program Operations Division of Extramural Research and Training National Institute of Environmental Health Sciences P.O. Box 12233 111 T. W. Alexander Drive, MD EC-22 Research Triangle Park, NC 27709 Telephone: (919) 541-7824 Fax: (919) 541-2860 Email: dolby@niehs.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.113. Awards are made under authorization of the Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and administered under the NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant recipients to provide a smoke-free workplace and promote the non-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.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices



NIH Office of Extramural Research Logo
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®



Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.