GENETIC ASPECTS OF TUBERCULOSIS IN THE LUNG Release Date: September 5, 2000 RFA: HL-00-014 National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov Letter of Intent Receipt Date: November 1, 2000 Application Receipt Date: January 17, 2001 THIS RFA USES "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS (these apply to the R01 grants). THE FULL RFA INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE FOLLOWED WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS RFA. PURPOSE The objective of this Request for Applications (RFA) is to stimulate research on the genetic aspects of tuberculosis, exploiting advances in molecular biology and genomics research. It is important to learn about the interaction between host and microbial genes, and to identify genes, or families of genes, that determine virulence, latency, reactivation of disease or resistance to antituberculous drugs. Areas of particular interest are studies using novel biotechnologies, such as microarrays, molecular beacon technology, or differential signature-tagged mutagenesis (DSTM) and innovative collaborations with computational biologists to identify genes that mediate the pathogenesis of tuberculosis and elucidate the mechanisms that are responsible. Another important goal of the program is to encourage junior level quantitative biologists to work on the genetic aspects of TB. To facilitate their participation the Mentored Quantitative Research Career Development Award (K25) has been included as one of the mechanisms of support under this RFA. Among the disciplines and expertise that may be appropriate for this research program are genetics, molecular biology, computational biology/mathematical modeling, biostatistics, pathogenesis of infections, immunology, lung cell biology, bacteriology, pulmonology, infectious diseases, pathology, epidemiology, and veterinary medicine. 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, "Genetic Aspects of Tuberculosis in the Lung," is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople/. ELIGIBILITY REQUIREMENTS R01 applications may be submitted by domestic and foreign, 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. Domestic institutions only, may submit applications for K25 awards. In addition, for K25 applications, former principal investigators on NIH research project (R01), program project (P01), center grants, FIRST Awards (R29), SBIR/STTR awards, sub-projects of program project (P01) or center grants, K01, K08 or K23 awards, or the equivalent are not eligible. Former principal investigators of an NIH Small Grant (R03) or Exploratory/Developmental Grants (R21) remain eligible. A candidate for the Mentored Quantitative Research Career Development Award may not concurrently apply for any other PHS award that duplicates the provisions of this award nor have another application pending award. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. All current policies and requirements that govern the research grant programs of the National Institutes of Health (NIH) will apply to grants awarded under this RFA. Awards under this RFA to foreign institutions will be made only for research of very unusual merit, need, and promise, and in accordance with PHS policy governing such awards. MECHANISM OF SUPPORT This RFA will use the NIH individual research project grant (R01) and the Mentored Quantitative Research Career Development Award (K25) mechanisms of support. A description of the K25 award is available on the web at: https://grants.nih.gov/grants/guide/pa-files/PA-99-087.html. Individuals may apply for either an R01 grant or a K25 award under this RFA, but cannot apply for both grants. Each application submitted for this RFA must be a complete, independent entity and not depend on any other application submitted in response to this RFA. Responsibility for the planning, direction, and execution of each of the proposed projects will be solely that of the respective applicant. The total project period for an application submitted in response to this RFA may not exceed 5 years. This RFA is a one-time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to the customary peer review procedures. The anticipated award date is July 1, 2001. Although multidisciplinary approaches are encouraged, it is not the intent of this RFA to solicit applications for large studies encompassing a variety of individual subprojects, i.e., program projects. If collaborative arrangements through subcontracts with other institutions are planned, consult the program staff listed under INQUIRIES. Biomedical investigators without prior R29 or R01 support are encouraged to apply for R01s under this RFA and to identify their status on the front of the grant application. Specific R01 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 https://grants.nih.gov/grants/funding/modular/modular.htm Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or principal investigator should be included with the application. FUNDS AVAILABLE It is anticipated that for fiscal year 2001, approximately $3.5 million, total costs, will be committed by NHLBI and $1.0 million, total costs, will be committed by NIAID, for this RFA. Award of grants pursuant to this RFA is contingent upon receipt of such funds for this purpose. It is anticipated that up to 10-12 new R01 grants will be awarded under this program and up to 4-6 new K25 grants will be awarded under this program. The specific numbers to be funded will, however, depend on the merit and scope of the applications received and on the availability of funds. For this RFA, funds for R01s must be requested in $25,000 direct cost modules and a maximum of 12 modules ($300,000 direct costs) per year may be requested. A feature of the modular grant concept is that no escalation is provided for future years, and all anticipated expenses for all years of the project must be included within the number of modules being requested. Only limited budgetary information will be required and any budget adjustments made by the Initial Review Group will be in modules of $25,000. For the K25 grants funded under this RFA, funding is determined by the allowable costs designated for the K25 type of award, salary of up to $75,000 per year plus fringe benefits and research development support of up to $40,000 per year for the following expenses: (a) tuition, fees, and books related to career development; (b) research expenses, such as supplies, equipment and technical personnel; c) travel to research meetings or training; (d) research support services including personnel and computer time. Ancillary Personnel Support: Salary for mentors, secretarial, and administrative assistance etc., is not allowed. Facilities and Administrative costs will be reimbursed at 8 percent of modified total direct costs. RESEARCH OBJECTIVES Background Tuberculosis continues to be a worldwide health problem. It is contagious, and can be difficult to diagnose and to treat. The lung is the usual portal of entry for Mycobacterium tuberculosis (Mtb) and the interactions that occur between the microbe and the lung defense system, at all stages of the infection, are pivotal in determining the subsequent course of the disease. For decades it has been understood that inherited host resistance factors, genetic differences in mycobacterial virulence, and differences in mycobacterial sensitivity to antituberculous drugs play a large part in determining the way in which tuberculosis manifests itself. Now we possess tools that may make it possible to elucidate the genetic control of host susceptibility and resistance to tuberculosis. These new techniques may allow us to learn about host and microbial genes as well as the interactions between them and to discover which ones play a role in determining host susceptibility or resistance to infection and reactivation of disease as well as microbial virulence, latency, and resistance to antituberculous drugs. Objectives and Scope The purpose of this RFA is to stimulate research on the genetic aspects of tuberculosis in the lung. More specifically, the RFA encourages the use of recent technological advances in molecular biology, genomics research and computational biology to learn more about host and mycobacterial genes and the interactions between them. The long-term goals of the RFA are to identify genes, or families of genes, that determine resistance and susceptibility to mycobacterial infection, virulence, latency, reactivation of disease and resistance to antituberculous drugs. This RFA program is particularly relevant to African American and Hispanic minority populations who are disproportionately affected by tuberculosis in comparison to the total population, possibly because of increased genetic susceptibility. In the last few years much progress has been made in understanding the genetics of the organism and the host, including: the genome of M. tuberculosis has been sequenced; the sequencing of the human genome is nearing completion; a tuberculosis resistance gene, the Bcg gene (Nramp1) has been identified and cloned both in mice and humans; mycobacterial genes that confer resistance to oxidants have been identified and cloned; and the Mtb rifampin resistance gene has been exploited to allow for rapid identification of drug resistant strains. In addition, molecular epidemiologic methods have allowed a far better understanding of the spread of disease during outbreaks of tuberculosis. However, much remains to be learned about the genetic factors, that determine interactions between the host and mycobacterium. Genetic technologies now available, including genetically altered animal models and microarray technology, may make it possible to identify both host and microbial genes, or clusters of genes, that mediate the pathogenesis of disease and further elucidate the mechanisms that are responsible. Skills of biostatisticians and other mathematicians using existing or novel mathematical techniques to design experimental approaches and interpret data may be necessary. Understanding the molecular biology of tuberculosis should lead to new possibilities for controlling the disease. In responding to this RFA expertise might be needed in the following areas: genetics, molecular biology, computational biology/mathematical modeling, biostatistics, pathogenesis of infections, immunology, lung cell biology, bacteriology, pulmonology, infectious diseases, pathology, epidemiology and veterinary medicine This RFA is co-sponsored by NHLBI and NIAID. NHLBI is most interested in encouraging research on the host lung response in M. tuberculosis infection, whereas NIAID is particularly interested in using this RFA to encourage research on the microbial genome and post genomic functional analysis to better understand TB pathogenesis. Of great interest to both NIAID and NHLBI are genes associated with latency and reactivation of disease, and with host- microbe interaction. Some examples of areas of research that might be included under this RFA are as follows: o Studies of gene expression in M. tuberculosis in animal (e.g. mouse, non- human primate, etc.) or human macrophages and other host cells during infection, using novel technologies such as molecular beacon RT-PCR, DNA microarrays, non-invasive imaging techniques (biophotonics) or any combination of these or other approaches. Such studies might address issues relating to metabolic state/stage of infection and therapeutic interventions. o Study genetic variations in M. tuberculosis and BCG and their relevance to patterns of disease and efficacy of vaccination. o Population based studies to analyze novel biologic characteristics of clinical strains of M. tuberculosis, as well as to study the human immune response to infection in a situation where a group of people are all infected with a single strain of M. tuberculosis. Can microbial and host genetic factors be identified that help to explain why some people develop tuberculosis, some convert their PPD skin reaction, some revert to PPD negativity? Investigators are encouraged to use already identified cohorts. o Studies in mice or other animal models to determine the differences of host cell gene expression in response to mycobacterial infection, in lung as compared to other organs (e.g., lung, liver, spleen, kidney) or in upper as compared to lower lung zones. o Studies in structural genomics, such as studies to determine protein structure and function of the entire set of gene products from the tuberculosis genome or identification of protein families involved in the pathogenesis of tuberculosis. o Use of genetically manipulated (e.g., transgenic, knock out) animals and novel biotechnologies to study the pathogenesis of pulmonary tuberculosis, and the factors that contribute to innate resistance to M. tuberculosis, to latency and to reactivation. o Studies involving collaboration with mathematicians (e.g., computational biologists) to develop new paradigms for examining interactions between the mycobacterial and host genomes. These are examples only. Investigators should not feel limited to the subjects mentioned above and are encouraged to submit other topics pertinent to the objectives of the RFA. Two additional goals of the RFA specific to the Mentored Quantitative Research Career Development Award, K25 awards, are as follows: o Encourage research-oriented quantitative scientists and engineers with little or no experience in biology or biomedicine to develop independent research skills and gain experience in advanced methods and experimental approaches that will allow them to conduct basic or clinical biomedical research related to the genetic aspects of tuberculosis or to play leading roles in multi-disciplinary research teams. o Increase the pool of quantitative researchers who can conduct biomedical research related to the genetic aspects of tuberculosis in the lung, capitalizing on the quantitative backgrounds of the investigators to inform new directions in this area of research. SPECIAL REQUIREMENTS K25 applicants must fulfill the eligibility requirements for the K25 award described at https://grants.nih.gov/grants/guide/pa-files/PA-99-087.html Special requirements for the K25 award pertain to the candidate, the mentor(s), the program, the environment and possible future evaluations. Upon initiation of the program, the NHLBI and NIAID will sponsor periodic meetings to encourage exchange of information among all funded investigators who participate in this program. A major goal of these meetings is to facilitate progress by providing a forum that will lead to sharing ideas, technology, data, skills, and biological materials. Applicants for both K25 and R01 awards must budget for travel funds that will allow principal investigators and other key research scientists to participate in these meetings. The meetings are usually one day meetings, held each year, in Bethesda, Maryland. Applicants must include a statement in their applications indicating their willingness to participate in these meetings. Animal models based on genetic manipulations (e.g., transgenic and knock out animals) are encouraged. Multidisciplinary approaches that include mathematical modeling are of particular interest. Research on human tissue is encouraged, however, large clinical or population based studies are not within the scope of this RFA. 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 sub-populations 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 (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); a complete copy of the updated Guidelines are available at https://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: https://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, by November 1, 2000, a letter of intent that includes a descriptive title of the proposed research, the type of application proposed (R01 or K25), 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 subsequent applications, the information that it contains allows NHLBI staff to begin to identify appropriate reviewers, to estimate the potential review workload and plan the review. The letter of intent is to be sent to Dr. Deborah P. Beebe listed under INQUIRIES by November 1, 2000. 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 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. 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 (GENETIC ASPECTS OF TUBERCULOSIS IN THE LUNG) and number (HL-00-014) 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 available at: https://grants.nih.gov/grants/funding/phs398/label-bk.pdf has 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 Dr. Deborah P. Beebe, at the address listed under INQUIRIES. Applications must be received by the application receipt date listed in the heading of this RFA, January 17, 2001. If an application is received 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. SPECIFIC INSTRUCTIONS FOR R01 APPLICANTS 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. BUDGET INSTRUCTIONS FOR R01 APPLICATIONS Modular grant applications will request direct costs in $25,000 modules, up to a total direct cost of $300,000 per year for all R01s. 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 $300,000) 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 https://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 key personnel, and the role on the project. Indicate whether the collaborating institution is foreign or domestic. The total cost 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: https://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. o OTHER SUPPORT - Do not complete the "Other Support" pages. Selected other support information relevant to the proposed research may be included in the Biographical Sketch as indicated above. Complete Other Support information will be requested by NHLBI staff if there is a possibility for an award. SPECIFIC INSTRUCTIONS FOR K25 APPLICATIONS An important goal of this RFA is to stimulate collaborations between quantitative scientists and biological scientists to investigate the genetics of tuberculosis. We want to encourage junior level quantitative biologists to do research on the genetics of TB. For this reason the K25 program, which fosters career development of mathematicians and engineers interested in biomedical research, has been included as a funding mechanism under this RFA. Some information on eligibility criteria for the K25 is summarized below. However, THOSE INTERESTED IN APPLYING FOR K25 AWARDS WILL NEED TO OBTAIN ADDITIONAL INFORMATION ON THE K25 GOALS, ELIGIBILITY, RESTRICTIONS AND SPECIAL REQUIREMENTS FROM THE K25 PROGRAM ANNOUNCEMENT, WHICH CAN BE FOUND AT: https://grants.nih.gov/grants/guide/pa-files/PA-99-087.html. The K25 awards are NOT modular. Applications for K25 awards under this RFA must use the RFA receipt date of January 17, 2001, NOT the application receipt dates stated in the PA-99-087. The K25 application budgets should be prepared in accordance with the allowable costs and instructions provided in PA-99-087. The K25 applications must follow the K25 guidelines and comply with the requirements for the K25. Just-in-time instructions apply to both the R01 and K25 mechanisms. o Special eligibility requirements apply to K25 Candidates applying for this RFA: They must have demonstrated research interests with an advanced degree in a quantitative area of science or engineering: M.S.E.E., Ph.D., D.Sc., etc. They must identify a mentor with extensive biomedical and/or computational biology research experience. The K25 candidates must be willing to spend at least 75 percent of full-time professional effort conducting research career development and basic or clinical research. K25 applicants experience in biomedical research may vary. Some may have very limited experience in biomedical research and require didactic training and a very closely supervised research experience. Other K25 applicants, with more experience, may require less class work and less supervision. Applications may be submitted on behalf of candidates, by DOMESTIC organizations, public or private, such as research foundations, research institutions, commercial entities, medical, dental, or nursing schools, Federal National Laboratories (except for laboratories of the National Institutes of Health), or other institutions of higher education. At time of the K25 AWARD, CANDIDATES MUST BE CITIZENS OR NONCITIZEN NATIONALS OF THE UNITED STATES, OR HAVE BEEN LAWFULLY ADMITTED TO THE UNITED STATES FOR PERMANENT RESIDENCE (I.E., IN POSSESSION OF A CURRENTLY VALID ALIEN REGISTRATION RECEIPT CARD I-551, OR OTHER LEGAL VERIFICATION OF SUCH STATUS). Noncitizen nationals are generally persons born in outlying possessions of the United States (i.e., American Samoa and Swains Island). Individuals on temporary or student visas are not eligible. o FORMER PRINCIPAL INVESTIGATORS on NIH research project (R01), program project (P01), center grants, FIRST Awards (R29), SBIR/STTR awards, sub-projects of program project (P01) or center grants, K01, K08 or K23 awards, or the equivalent are NOT ELIGIBLE FOR THE K25 AWARD. FORMER PRINCIPAL INVESTIGATORS of an NIH Small Grant (R03) or Exploratory/Developmental Grants (R21) REMAIN ELIGIBLE. A candidate for the Mentored Quantitative Research Career Development Award may not concurrently apply for any other PHS award that duplicates the provisions of this award nor have another application pending award. Mentored Quantitative Research Career Development Award recipients are strongly encouraged to apply for independent research grant support, either Federal or private, during the latter period of this K25 award. However, since the K25 is a full professional effort award, time conducting additional research directly related to this award is subsumed under the salary support already provided by this award. THE K25 APPLICATION MUST CONTAIN THE FOLLOWING: Candidate (K25) o A description of the candidate's commitment to a career in quantitative biomedical, behavioral, or bioengineering research o Evidence of the candidate's interest in conducting research o Evidence of the candidate's potential to develop into an independent investigator o A description of immediate and long-term career objectives, explaining how the award will contribute to their attainment o A commitment of at least 75 percent effort to this research program o Three sealed letters of recommendation addressing the candidate's potential for a research career in quantitative biomedicine or bioengineering. The mentor's statement (see below) should not be included as one of the letters of recommendation, although the mentor(s) may submit a separate letter(s) of recommendation. Career Development Plan (K25) o A description of the career development plan, incorporating consideration of the candidate's goals and prior experience. It must describe a systematic plan to obtain the necessary theoretical and conceptual background, in addition to the research experience, necessary to launch an independent research career in quantitative biomedicine or bioengineering. o Candidates must describe the availability of courses important to their career development plan at their institution and the manner of integration of these studies into their career development plan. o The career development plan must be tailored to the needs of the individual candidate and the ultimate goal of achieving independence as a researcher in quantitative biomedicine or bioengineering. Less experienced candidates may require a phased developmental period in which the first one to two year(s) of the award are largely of a didactic nature followed by a period of intense, supervised research. Candidates with more experience at the time of application may need a shorter developmental period and may already have an adequate theoretical background. o Candidates must describe plans to receive instruction in the responsible conduct of research. These plans must detail the proposed subject matter, format, frequency, and duration of instruction. No award will be made if an application lacks this component. Research Plan (K25) o A description of the quantitative biomedical, behavioral, or bioengineering research plan. The research plan must be described as outlined in form PHS 398, including sections on the Specific Aims, Background and Significance, Progress Report/Preliminary Studies, Research Design and Methods. The candidate should consult with the mentor regarding the development of this section. Mentor's Statement (K25) o The application must include information on the mentor(s), including information on basic or clinical biomedical research qualifications in the research area proposed by the candidate and previous experience as a research supervisor. The application must also include information to describe the nature and extent of supervision that will occur during the proposed award period. Mentors may be employed in any sector of the biomedical research community (e.g., academia, industry, non-profit research institutions). Environment and Institutional Commitment (K25) o The sponsoring institution must document a strong, well-established research and training program related to the candidate's area of interest, including a high-quality research environment with staff capable of productive collaboration with the candidate. The sponsoring institution also must provide a statement of commitment to the candidate's development into a productive, independent investigator. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the CSR and for responsiveness by the NHLBI and NIAID. 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 NHLBI in accordance with the review criteria stated below. The roster of reviewers for the RFA will be available on the NHLBI home page approximately four weeks prior to the scheduled review date. As part of the initial merit review, a process will be used by the initial review group in which all 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 Heart, Lung, and Blood Advisory Council or the National Institute of Allergy and Infectious Diseases Advisory Council. REVIEW CRITERIA FOR R01 APPLICATIONS 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 review, comments on the following aspects of the application will be made 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, weighting 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 study 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: 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 method? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? (4) Investigator: Is the investigator 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? The personnel category will be reviewed for appropriate staffing based on the requested percent effort and justification provided. For R01 applications, the direct costs budget request will be reviewed for consistency with the proposed methods and specific aims. Any budgetary adjustments recommended by the reviewers will be in $25,000 modules. The duration of support will be reviewed to determine if it is appropriate to ensure successful completion of the requested scope of the project. REVIEW CRITERIA FOR K25 APPLICATIONS: The following review criteria will be applied: Candidate o Quality of the candidate's academic and research record; o Potential to develop as an independent quantitative biomedical or bioengineering researcher or to play significant role in multi-disciplinary research teams; and o Commitment to a career in quantitative biomedical or bioengineering research. Career Development Plan o Likelihood that the career development plan will contribute substantially to the scientific development of the candidate; o Appropriateness of the content and duration of the proposed didactic and research phases of the award; o Consistency of the career development plan with the candidate's career goals and prior research experience; and o Quality of the proposed training in responsible conduct of research. Research Plan Reviewers recognize that an individual with limited research experience is less likely to be able to prepare a research plan with the breadth and depth of that submitted by a more experienced investigator. Although it is understood that K25 applications do not require the level of detail necessary in regular research grant applications, a fundamentally sound research plan must be provided. In general, less detail is expected with regard to research planned for the later years of the award, but the application should outline the general goals for these years. o Appropriateness of the research plan to the stage of research development and as a vehicle for developing the research skills as described in the career development plan; o Scientific and technical merit of the research question, design and methodology; o Relevance of the proposed research to the candidate's career objectives; o Adequacy of the plan's attention to gender and minority issues associated with projects involving human subjects; and o Adequacy of plans for including children as appropriate for the scientific goals of the research, or justification for exclusion. Mentor o History of research productivity and support in the area of basic or clinical biomedical research; o Appropriateness of mentor's research qualifications in the area of this application; o Quality and extent of mentor's proposed role in providing guidance and advice to the candidate; and o Previous experience in fostering the development of researchers. Environment and Institutional Commitment o Applicant institution's commitment to the scientific development of the candidate and assurances that the institution intends the candidate to be an integral part of its research program; o Adequacy of research facilities and the availability of appropriate educational opportunities (including access to such facilities or opportunities in other institutions); o Quality and relevance of the environment for scientific and professional development of the candidate; and o Applicant institution's commitment to an appropriate balance of research and other responsibilities. Budget o Justification of the requested budget in relation to career development goals and research aims. In addition to the above criteria, in accordance with NIH policy, all R01 and K25 applications will also be reviewed with respect to the following: o The adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research will be reviewed. 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, animals or the environment, to the extent they may be adversely affected by the project proposed in the application. SCHEDULE Letter of Intent Receipt Date: November 1, 2000 Application Receipt Date: January 17, 2001 Council Review: June 14-15, 2001 Anticipated Start Date: July 1, 2001 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. Applicants should be aware that, in addition to scientific merit, program priorities and program balance, the total costs of the proposed project and the availability of funds will be considered by the awarding Institutes in making funding recommendations. The Institutes may fund individual applications based on a number of considerations, the most important of which are based on their scientific merit and their importance in meeting the objectives of the RFA. Applications from new investigators will be strongly considered. INQUIRIES Inquiries concerning this RFA are strongly encouraged. Potential applicants should request a copy of the sample budget pages. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Hannah H. Peavy, M.D. Division of Lung Diseases National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Suite 10018, MSC 7952 Bethesda, MD 20892-7952 Telephone: (301) 435-0222 FAX: (301) 480-3557 E-mail: peavyh@nih.gov Or Susan Garfinkel, Ph.D. Division of Lung Diseases National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Suite 10018, MSC 7952 Bethesda, MD 20892-7952 Telephone: (301) 435-0222 FAX: (301) 480-3557 E-mail: garfinks@nih.gov Or Ann M. Ginsberg, M.D., Ph.D. Division of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases 6700-B Rockledge Drive, room 3131, MSC 7630 Bethesda, MD 20892-7630 Telephone: (301) 496-5305 FAX: (301) 496-8030 Email: ag73i@nih.gov Direct inquiries regarding fiscal matters (e.g., sample budget pages) to: Ms. Tara Mowery Division Extramural Affairs National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7163, MSC 7926 Bethesda, MD 20892-7926 Telephone: (301) 435-5081 FAX: (301) 480-3310 Email: moweryt@nhlbi.nih.gov Inquires regarding review, letters of intent and two copies of the grant application should be directed to: Deborah P. Beebe, Ph.D. Division of Extramural Affairs National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7178, MSC 7924 Bethesda, MD 20892-7924 Telephone: (301) 435-0270 FAX: (301) 480-3541 E-mail: beebed@nhlbi.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, Nos. 93.838 and 93.361. Awards are made under authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 UC241 and 284) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 72 and CFR 52 and 45 CFR Part 74 for NIAID. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or a Health Systems Agency Review. The PHS strongly encourages all grant and contract 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.
Return to NIH Guide Main Index
Office of Extramural Research (OER) |
National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892 |
Department of Health and Human Services (HHS) |
||||||||