and Human Services (HHS)
EXPIRED
EVOLUTIONARY MECHANISMS IN INFECTIOUS DISEASE RELEASE DATE: PA NUMBER: PA-02-113 (This PA has been reissued, see PA-05-079) EXPIRATION DATE: March 29, 2005 National Institute of General Medical Sciences (http://www.nigms.nih.gov/) National Institute of Diabetes and Digestive and Kidney Diseases (http://www.niddk.nih.gov/) THIS PA CONTAINS THE FOLLOWING INFORMATION o Purpose of the PA o Research Objectives o Mechanism(s) of Support o Eligible Institutions o Individuals Eligible to Become Principal Investigators o Where to Send Inquiries o Submitting an Application o Peer Review Process o Review Criteria o Award Criteria o Required Federal Citations PURPOSE The goal of the announcement is to encourage development of a predictive science of infectious disease by applying the perspectives, theories, and methods from relevant scientific disciplines to important issues of disease emergence, prevention, and the consequences of treatment. Research projects involving interdisciplinary collaborations are an explicit goal of this announcement. Approaches might include, but are not limited to, evolutionary biology, microbiology, population dynamics, chemistry, biochemistry, and computational biology. The focus is limited to discovery of fundamental biological principles rather than to detailed knowledge or treatment of specific diseases. RESEARCH OBJECTIVES Background A predictive science of infectious disease depends on our ability to anticipate with some confidence the behavior of host/parasite systems. Predictions might include when and where new infectious diseases will emerge, under what conditions drug resistance will arise, the consequences of therapeutic interventions, and the impact of ecological changes. The rise of infectious systems consisting of parasite(s), vector(s), and host(s) are subject to dynamic interactions at many levels from the chemical to the populational. For example, the ability of an infectious species to colonize plant or animal hosts, to proliferate, to cause disease, and to spread depends on a variety of factors, such as its genetic characteristics, its life history, and its mode of transmission, all of which are subject to evolutionary change. The ability of a host species to prevent, control, and/or promote interactions similarly depends on its innate defense system (including immune defenses), its behavior, its environment, and human intervention. Population dynamics, including population density, migration, population subdivision, and competition for resources, affect the evolution of pathogens, vectors, and hosts. Evolutionary biology, molecular biology, genetics, systematics, chemistry, biochemistry, mathematics, and other disciplines, will contribute significantly to the development of a predictive science of infectious systems. For example, identifying the origins and host ranges of infectious agents requires a variety of molecular, genetic, mathematical, and evolutionary tools. Intervention to prevent or treat infections by behavior modification, control of vectors, vaccination, drug therapy or other means influences a variety of dynamic evolutionary processes in individual hosts, communities of hosts, and communities of pathogenic organisms. Understanding the conditions under which interventions fail (e.g., antibiotic resistance or reversion of live vaccines to virulence) and designing protocols to prevent these failures requires application of evolutionary understanding. Multidisciplinary approaches are essential for anticipating the conditions under which new infectious diseases will emerge and old ones will re- emerge. While there is widespread interest in understanding, preventing, and treating infectious diseases and anticipating their emergence and re-emergence, research into evolutionary aspects of infectious systems has been limited. With a few exceptions, broad interdisciplinary approaches are rarely employed in infectious disease research or in the design of protocols to prevent and treat infections. The goal of this initiative is to remedy this situation by supporting collaborations among scientists with diverse areas of expertise. Scientific Objectives Proposals for research projects responsive to this announcement should address broad evolutionary questions that are relevant to infectious disease in general. Because host/parasite and other symbiotic systems exhibit a continuum of behavior, ranging from beneficial to pathological associations, general evolutionary principles can be expected to emerge from studies using a variety of models. For this reason, a variety of model systems, including plant and microbial systems will also be considered when they are used to address fundamental mechanisms of evolution. Human studies are included when the goal of the research is basic knowledge of the evolution of infectious systems rather than of a specific disease entity. Studies that combine quantitative, theoretical, and experimental approaches are especially encouraged. Applicants must clearly explain how the proposed approaches and perspectives are expected to contribute to development of a predictive science of infectious disease. Within the areas of investigation described below, relevant applications could focus on, but are not limited to, one or more of the following aspects: 1. Causes and sources of infectious disease. o Genetic variation and structure of pathogen populations and the genetic relationships between commensal and pathogenic members of closely related taxa o Population analyses of the contributions and sources of the vertical and horizontal transfer of genes and accessory elements coding for virulence determinants, host range and specificity, and drug resistance o Genetic factors (pathogen, host, or vector) responsible for geographic and temporal variation in disease frequency and severity 2. Interactions between hosts and pathogens. o Contribution of population dynamic and evolutionary processes to the pathogenesis and virulence of infecting organisms o Establishment of model systems to explore the relationship between the evolution of pathogenic organisms and factors affecting host susceptibility, including ecological, social, and other environmental factors o Mechanisms of chemical signaling and communication 3. Consequences of intervention strategies. o Within-host population dynamics related to intervention strategies, including reversion to virulence of live vaccines (as opposed to outgrowth of existing unattenuated organisms), as well as evolution of resistance following antimicrobial drug therapy or vaccination o Establishment of model systems (either in vitro systems, or in vivo systems involving non-human pathogens and/or animal, microbe, or plant hosts) to predict the ecological and evolutionary consequences of programs involving host behavior, vaccination, antimicrobial drug therapy, and other intervention strategies on pathogen, host, and vector populations o Novel mechanisms of antibiotic action o Use of evolutionary approaches to create new strategies for drug development and delivery o Identification of new resistance mechanisms, including how they arose 4. Establishment of model systems to explore the environmental, physiological and genetic factors responsible for generating and maintaining variation in pathogen, vector, and host populations, including co-evolutionary dynamics. 5. Natural history of pathogenic organisms. o Evolutionary basis for the normal range of pathogen habitats and hosts o Establishment of model systems to explore the molecular basis of host barriers that must be overcome by pathogens in order to extend their ranges o Establishment of model systems to explore the molecular, individual, and population dynamics of extending the niche or host range of a pathogen. MECHANISM OF SUPPORT This PA will use the National Institutes of Health (NIH) research project grant (R01). As an applicant, you will be solely responsible for planning, directing, and executing the proposed project. Supplements to existing NIH grants will also be considered. The total project period for an application submitted in response to this PA may not exceed five years. This PA uses just-in-time concepts. It also uses the modular as well as the non-modular budgeting formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if you are submitting an application with direct costs in each year of $250,000 or less, use the modular format. Otherwise follow the instructions for non- modular research grant applications. ELIGIBILITY REQUIREMENTS You may submit (an) application(s) 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 institutions 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. WHERE TO SEND INQUIRIES We encourage your inquiries concerning this PA and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into two areas: scientific/research and financial or grants management issues: o Direct your questions about scientific/research issues to: Dr. Irene Anne Eckstrand Division of Genetics and Developmental Biology National Institute of General Medical Sciences Building 45 Center Drive, Room MSC 6200 Bethesda, MD 20892 Telephone: (301) 594-0943 FAX: (301) 480-2228 Email: [email protected] Frank A. Hamilton, M.D., MPH Division of Digestive Diseases and Nutrition National Institute of Diabetes and Digestive and Kidney Diseases 6707 Democracy Blvd., Democracy 2, Room 669 Bethesda, Maryland 20892-5450 Telephone: (301) 594-8877 FAX : (301) 480-8300 Email: [email protected] o Direct your questions about financial or grants management matters to: Ms. Marcia Cohn Grants Management Office National Institute of General Medical Sciences Building 45 Center Drive, Room MSC 6200 Bethesda, MD 20892 Telephone: (301) 594-3918 FAX: (301) 480-1969 Email: [email protected] Ms. Carolyn Kofa Grants Management Branch Division of Extramural Activities National Institutes of Diabetes and Digestive and Kidney Diseases 6707 Democracy Blvd. 2 Democracy Plaza, Room 727 Bethesda, Maryland 20892 Telephone: (301) 594-6787 FAX: (301) 480-3604 Email: [email protected] 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 http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: [email protected]. APPLICATION RECEIPT DATES: Applications submitted in response to this program announcement will be accepted at the standard application deadlines, which are available at http://grants.nih.gov/grants/dates.htm. Application deadlines are also indicated in the PHS 398 application kit. SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications requesting up to $250,000 per year in direct costs 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 http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step guidance for preparing modular grants. Additional information on modular grants is available at http://grants.nih.gov/grants/funding/modular/modular.htm. SPECIFIC INSTRUCTIONS FOR APPLICATIONS REQUESTING $500,000 OR MORE PER YEAR: Applications requesting $500,000 or more in direct costs for any year must include a cover letter identifying the NIH staff member within one of NIH institutes or centers who has agreed to accept assignment of the application. Applicants requesting more than $500,000 must carry out the following steps: 1) Contact the IC program staff at least 6 weeks before submitting the application, i.e., as you are developing plans for the study, 2) Obtain agreement from the IC staff that the IC will accept your application for consideration for award, and, 3) Identify, in a cover letter sent with the application, the staff member and IC who agreed to accept assignment of the application. This policy applies to all investigator-initiated new (type 1), competing continuation (type 2), competing supplement, or any amended or revised version of these grant application types. Additional information on this policy is available in the NIH Guide for Grants and Contracts, October 19, 2001 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html. SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of the application, including the checklist, and five 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) APPLICATION PROCESSING: Applications must be received by or mailed on or before the receipt dates described at http://grants.nih.gov/grants/funding/submissionschedule.htm. The CSR will not accept any application in response to this PA 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 a substantial revision of an application already reviewed, but such application must include an Introduction addressing the previous critique. PEER REVIEW PROCESS Applications submitted for this PA will be assigned on the basis of established PHS referral guidelines. An appropriate scientific review group convened in accordance with the standard NIH peer review procedures (http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific and technical merit. As part of the initial merit review, all applications will: o Receive a written critique o Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score o Receive a second level review by the appropriate national advisory council or board 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? ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your application will also be reviewed with respect to the following: 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. INCLUSION: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. (See Inclusion Criteria included in the section on Federal Citations, below) DATA SHARING: The adequacy of the proposed plan to share data. BUDGET: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. AWARD CRITERIA Applications submitted in response to a PA will compete for available funds with all other recommended applications. The following will be considered in making funding decisions: o Scientific merit of the proposed project as determined by peer review o Availability of funds o Relevance to program priorities REQUIRED FEDERAL CITATIONS INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: 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 clinical research projects unless a clear and compelling justification is 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 clinical research should read the AMENDMENT "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research - Amended, October, 2001," published in the NIH Guide for Grants and Contracts on October 9, 2001 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html), a complete copy of the updated Guidelines are available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm . The amended policy incorporates: the use of an NIH definition of clinical research, updated racial and ethnic categories in compliance with the new OMB standards, clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398, and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must 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) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: The NIH maintains a policy 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 is available at http://grants.nih.gov/grants/funding/children/children.htm. REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH policy requires education on the protection of human subject participants for all investigators submitting NIH proposals for research involving human subjects. You will find this policy announcement in the NIH Guide for Grants and Contracts Announcement, dated June 5, 2000, at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html. HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on hESCs can be found at http://grants.nih.gov/grants/stem_cells.htm and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (see http://escr.nih.gov). It is the responsibility of the applicant to provide the official NIH identifier(s)for the hESC line(s)to be used in the proposed research. Applications that do not provide this information will be returned without review. 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 http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this PA 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 PA 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. AUTHORITY AND REGULATIONS: This program is described in the Catalog of Federal Domestic Assistance No. 93.862, 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 administered under NIH grants policies described at http://grants.nih.gov/grants/policy/policy.htm and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. 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.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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