and Human Services (HHS)
EXPIRED
NOVEL GENETIC METHODS TO MAP FUNCTIONAL NEURONAL CIRCUITS AND SYNAPTIC CHANGE RELEASE DATE: October 10, 2002 PA NUMBER: PAR-03-007 (see change NOT-DA-04-003) APPLICATION RECEIPT DATE: The receipt dates for this Program Announcement are: February 12, 2003, February 12, 2004, and February 14, 2005. National Institute on Drug Abuse (NIDA) (http://www.nida.nih.gov) National Institute on Aging (NIA) (http://www.nia.nih.gov) National Institute of Alcohol Abuse and Alcoholism (NIAAA) (http://www.niaaa.nih.gov) National Institute on Deafness and Other Communication Disorders (NIDCD) (http://www.nidcd.nih.gov) National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) (http://www.niddk.nih.gov) National Eye Institute (NEI) (http://www.nei.nih.gov) National Institute of Mental Health (NIMH) (http://www.nimh.nih.gov) National Institute of Neurological Disorders and Stroke (NINDS) (http://www.ninds.nih.gov) National Institute of Child Health and Human Development (NICHD) (http://www.nichd.nih.gov) THIS PROGRAM ANNOUNCEMENT (PA) CONTAINS THE FOLLOWING INFORMATION o Purpose of the PA o Research Objectives o Mechanisms of Support o Eligible Institutions o Individuals Eligible to Become Principal Investigators o Special Requirements o Where to Send Inquiries o Submitting an Application o Peer Review Process o Review Criteria o Award Criteria o Required Federal Citations PURPOSE OF THIS PA This PA solicits applications to develop new genetic-based methods and technologies for the purpose of mapping functional neuronal circuits and synaptic changes in the mammalian nervous system. Emerging genetic and transgenic technologies can be used to single out functionally related cells or neuronal populations for analysis or intervention. This PA would support the development of genetic-based tools to map neuronal interconnectivity, to monitor functional changes, or to drive functional changes within neuronal circuits as the first step in an effort by the NIH to create integrated genomic and functional connectivity maps of the mammalian nervous system. Other corollary efforts needed to generate integrated connectivity maps such as improved neuroinformatics and the development of a large consortia of investigators, however, are outside the scope of this program announcement. Wide distribution to the scientific community of the methods and resulting resources developed under this program is essential for the eventual goal of creating large-scale functional connectivity maps of the mammalian nervous system. The unrestricted distribution of methods and resources developed under this program will also facilitate the rapid transfer of technology for the development of diagnostic tools and treatment interventions for brain disease. RESEARCH OBJECTIVES Background In January 2002, the National Institute of Mental Health (NIMH), the National Institute on Drug Abuse (NIDA), and the National Institute of Neurological Disorders and Stroke (NINDS) held a meeting at Laguna Beach, California, on "Setting Priorities for Functional Molecular Neuroanatomy in the Post-Genomic Era" http://trans.nih.gov/bmap/reports/reports.htm. One of the major recommendations from the meeting is for the National Institutes of Health (NIH) to develop initiatives directed toward mapping the functional neuronal circuits and plastic changes in the brain using powerful new genetic-based strategies. Highest priority was given to mapping functional circuits in the mouse and other mammalian systems that are amenable to genetic manipulation and intervention. It was recognized that an important first step toward this goal is the further development of genetic-based methods and technologies for this purpose. Understanding the pattern of interconnections of specific neural cells is essential to understanding their roles in nervous system function and dysfunction. Traditionally, the connections a neuron makes have been identified using electrophysiological recordings, from histochemical techniques or through the use of anterograde or retrograde tracers that make it possible to visualize the patterns of projections of individual neurons. While these approaches have been useful to identify certain aspects of neural connectivity, their utility is limited by their invasiveness, unavoidable confounding artifacts, and the inability to reproduce findings with great fidelity. Methods for mapping functional activity in neuronal circuits also suffer limitations, particularly with respect to resolution in space and time. For example, Positron Emission Tomographic imaging using radioactive deoxyglucose is limited in both temporal and spatial resolution. The use of early immediate genes, such as fos, to detect neuronal activity has high cellular resolution but the temporal resolution of this method is limited. Magnetic Resonance Imaging (MRI), on the other hand, reveals the activation of specific brain areas but does not permit an analysis of functionally interconnected neuronal circuits, and the relationship between MRI-detected activation and neuronal activity is not well understood. Other technologies used to study functional activity, such as voltage sensitive dyes and calcium indicators, provide good temporal and spatial resolution, but also pose technical obstacles. These include toxicity, lack of dye penetration into the cells of interest, and chemical degradation of the dye once inside the cell. Current methods for manipulating activity in neuronal circuits are crude. These include electrolytic or mechanical lesions, microinjection of tetrodotoxin or other neurotoxic agents into target areas, and the local administration of anesthetics or other pharmacologic agents. Many of these manipulations, however, are not reversible, difficult to control, and frequently disrupt more than one neuronal circuit. Despite the importance that plasticity plays in brain function, dysfunction, and recovery from injury, existing methods do not permit the visualization of dynamic or fluctuating changes at central synapses that may occur over prolonged time periods or the altered network properties that accompany learning and memory; nor do methods exist to image dynamic changes between neuronal connections during development, learning, aging, adaptation to chronic exposure to drugs, etc. Thus, new methods are needed if the process of plasticity is to be better understood at all levels of organization, from the subcellular to the systems level. Powerful new genetic approaches offer new opportunities to overcome many of the obstacles described or alluded to above. For example, subpopulations of neurons are increasingly being distinguished based on their pattern of gene expression. Cell-type specific promoters, therefore, allow the isolation of functionally related cells or neuronal populations, and can be used to trace the connections of these cells by driving the expression of genetically- encoded markers of neural connectivity (e.g., green fluorescent protein and its variants). Much effort is currently being devoted to devising genetically-encoded tracers that are transported across synapses and thus permit transsynaptic tracing of connections, both anterogradely and retrogradely, allowing extended, multisynaptic patterns of neural connectivity to be defined. Other studies have suggested the feasibility of using virus-assisted mapping of neuronal circuits that can be activated by focal injections of a catalyst or by electromagnetic radiation. A powerful variation on this theme is the recent development of a recombinant viral vector that is dependent on a Cre recombinase for replication and for expression of a genetically-encoded reporter. Potentially even more powerful are genetically-encoded reporters that can be used to monitor neural activity, the activity of signal transduction pathways, transmitter release, or other functional changes within neurons (e.g., Clomeleon, FlaSH, cameleons and synapto-pHluorins using optical or FRET-based approaches). Technologies like these have the potential to dramatically facilitate the mapping of functional neuronal circuits in the complex environment of the brain. Recent studies also suggest that genetic approaches can be used to alter or drive patterns of neural activity or signaling responses in defined neuronal populations. Transfection of neurons with the phototransduction apparatus has been shown to confer white light responsiveness within selected groups of neurons. This has worked in vitro but has not yet been tested in vivo. The ability to successfully activate selected neurons and their neural circuits in vivo in response to penetrating radio waves, light, or a magnetic field would be a very powerful technology for understanding the function of these selected neurons and neural circuits in the awake behaving animal. The primary goal of this program announcement, then, is to support the development of novel (or significantly improve existing) genetic-based methods and technologies for the purpose of mapping functional neuronal circuits and synaptic changes in the mammalian nervous system. The R21 mechanism is intended for feasibility studies while the R01 mechanism is intended for the development and initial application of these methods to mammalian model systems. Research Scope The types of projects supported by this initiative include but are not limited to: o Development of cell-type specific promoters or improvement of BAC technology to specifically label or isolate distinct neuronal classes and their projections for the purpose of mapping functional neuronal circuits (e.g., Fugu promoters, BAC clones to drive cell-specific expression of markers or reporters); o Development or improvement of genetic-based methods to map neuronal circuits and identify the afferents and efferents of defined neuronal populations including complex patterns of interconnectivity (e.g., using optical indicators or other genetically-encoded reporters coupled to a cell- type specific promoter); o Methods for detecting electrical activity in mammalian neurons by optical recording from genetically-encoded reporters (e.g., membrane potential sensors, calcium indicators, etc.); o Methods for detecting neuronal activity in deep brain structures using genetically-encoded reporters particularly suited for in vivo applications (e.g., caged contrast agents for magnetic resonance imaging, expression of bacterial genes involved in magnetic particle synthesis); o Methods for visualizing the activity of signal transduction pathways in neurons and neuronal circuits using genetically-encoded reporters or other fusion constructs (e.g., using FRET-based or other optical technologies); o Genetic-based methods for the persistent labeling of neurons over prolonged periods of time in order to follow plastic changes in morphology, connections or function; o Genetic-based methods for visualizing dynamic changes in neuronal connections, such as pulse-chase labeling of synapses (e.g., using different colors of fluorophores to label older and younger protein molecules); o Methods to correlate the genetic expression profile of a cell or defined neuronal population with its pattern of neuronal activity and neuronal interconnectivity; or conversely, to develop better in vivo methods for detecting alterations in gene expression that are induced by neural activity or other means; o Genetic-based methods for controlling or driving neural activity or signaling responses in defined neuronal populations (e.g., using genetically- encoded modulators of electrical activity that can be activated by specific signals such as pharmacological agents or light). MECHANISMS OF SUPPORT This PA will use the NIH research project grant (R01) and exploratory/developmental grant (R21) award mechanisms. The R21 mechanism is intended to encourage exploratory research projects where sound methodology and strong rationales exist, but for which preliminary data do not. Applicants should note that the R21 grant is limited to $100,000 for direct costs (including facilities and administrative costs on consortium arrangements, if any) per year up to three years. The R01 mechanism should be used in cases where the applicant has developed a body of preliminary data or previous methods or technology upon which the application will build. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. This PA is a three-time solicitation. Competing continuation applications if submitted in response to this PA, will compete with all investigator-initiated applications and be referred and reviewed according to the customary peer review procedures. The earliest anticipated award date is September 30, 2003. FUNDS AVAILABLE The participating institutes will commit a minimum of $1,100,000 in total costs [direct plus Facilities and Administrative (F & A) costs] in FY 2003 to fund 5 to 6 new grants in response to this PA. Applicants may use the dollars available and anticipated number of awards as a guide to develop reasonable budgets for their research projects. For an exploratory/development grant (R21), an applicant may request a budget for direct costs of up to $100,000 per year, including F & A costs on consortium arrangements for up to three years. This PA uses just-in-time concepts. It also uses the modular and 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. Because the nature and scope of the research proposed may vary, it is anticipated that the size of awards also will vary. Although the financial plans of the participating institutes provide support for this program, awards pursuant to this PA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. ELIGIBLE INSTITUTIONS 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 o Foreign INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs. SPECIAL REQUIREMENTS Restricted availability of unique research resources upon which further studies are dependent can impede the advancement of research and delivery of medical care. The sharing of biomaterials, data, and software in a timely manner, on the other hand, has been an essential element in the rapid progress that has been made in the genetic analysis of mammalian genomes. NIH policy requires investigators to make unique research resources readily available for research purposes to qualified individuals within the scientific community when they have been published [NIH Grants Policy Statement (http://grants.nih.gov/grants/policy/nihgps/); Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources: Final Notice, December 1999 (http://www.nih.gov/od/ott/RTguide_final.html)]. Biomaterials and other patentable research resources (e.g., genetically encoded reporters, vectors, embryonic cell lines, etc.) produced in projects funded by this PA are expected to be made available and distributed to the broader scientific community. The NIH is interested in ensuring that the research resources developed through this PA become readily available to the research community for further research, development, and application, in the expectation that this will lead to products and knowledge of benefit to the public. For this reason, NIH is concerned that patents on the vectors, mutagenesis methods, cell lines, and other research resources might have a chilling effect on the future development of products and information that may improve the public health. At the same time, NIH recognizes the rights of grantees to elect and retain title to subject inventions developed under federal funding under the provision of the Bayh-Dole Act. There are two special requirements for this PA regarding research resources produced in proposed projects: (1) Applicants are required to include in their application a specific plan by which they will share research resources with the wider scientific community. (2) Applicants are required to include a plan addressing if, or how, they will exercise their intellectual property rights while making available to the broader scientific community patentable research resources. These plans should be consistent with the policies of their institutional offices of technology transfer. Applicants are encouraged to discuss their proposed plans for addressing these requirements with their institutional offices of technology transfer. Each of the two requirements is discussed in detail below. Plan to Share Research Resources To address the joint interests of the government in the availability of, and access to, the results of publicly funded research, NIH requires applicants, who respond to this PA to propose detailed plans for sharing the research resources generated through the grant. It is expected that the resources to be shared include all materials developed in projects funded under the PA. A reasonable time frame for release of materials should be specified in the application and will be considered during the review of the plan for sharing. It is expected that the investigator's data and biomaterials sharing plan will include the access to biomaterials and methods not currently available to the wider scientific community. It is also expected that the investigator's data, papers, and biomaterials will be linked to the Brain Molecular Anatomy Project (BMAP) web page http://trans.nih.gov/bmap/. The scientific review group will evaluate the adequacy of the proposed plan for sharing and data access. Comments on the plan and any concerns will be presented in an administrative note in the Summary Statement. The adequacy of the plan will be considered by NIH program staff and will be important in determining whether the grant shall be awarded. The sharing plan approved by program staff, after negotiation with the applicant when necessary, will become part of the terms and conditions of the award. NIH program staff will evaluate the compliance with the sharing plan and scientific progress in the non-competing continuation of the grant award application. Intellectual Property Rights NIH is interested in ensuring that the research resources developed through this PA become readily available to the research community. With regard to patentable research results, such as genetically encoded reporters, cell lines, and vectors, the NIH requires applicants who respond to this PA to develop a plan addressing if, or how, they will exercise their intellectual property rights while making available to the broader scientific community research resources produced in projects funded under this PA. This is expected to include an elaboration of the applicant's anticipated plans to generate, or not generate, patents and/or exclusive or non-exclusive licensing of biomaterials and other patentable subject matter created in projects funded under this PA. This plan should be consistent with the applicant's institution's policies on intellectual property rights. This plan is also expected to include disclosure of any pre-existing agreements involving intellectual property rights, including options to for- profit research sponsors that are associated with biomaterials and data that may be generated. The requirement for this plan is in addition to the requirement for the plan for sharing and disseminating research resources described in the previous section. The majority of transfers to not-for-profit entities should be implemented under terms no more restrictive than the Uniform Biological Materials Transfer Agreement (UBMTA). In particular, recipients are expected to use the Simple Letter Agreement provided at http://www.nih.gov/od/ott/RTguide_final.htm, or another document with no more restrictive terms, to readily transfer unpatented tools developed with NIH funds to other recipients for use in NIH-funded projects. If the materials are patented or licensed to an exclusive provider, other arrangements may be used, but commercialization option rights, royalty reach-through, or product reach-through rights back to the provider are inappropriate. Similarly, when for-profit entities are seeking access to NIH-funded tools for internal use purposes, recipients should ensure that the tools are transferred with the fewest encumbrances possible. The Simple Letter Agreement may be expanded for use in transferring tools to for-profit entities, or simple internal use license agreements with execution or annual use fees may be appropriate. The scientific review group will evaluate the adequacy of the proposed plan for handling intellectual property rights. Comments on the plan and any concerns will be presented in an administrative note in the Summary Statement. NIH program staff in determining whether the grant shall be awarded will consider the adequacy of the proposed plan. The plan as approved, after negotiation with the applicant when necessary, will be a condition of the award. Evaluation of non-competing continuation applications will include assessment of the awardee's adherence to the proposed plan. Applicants also are reminded that the grantee institution is required to disclose each subject invention to NIH within two months after the inventor discloses it in writing to grantee institutional personnel responsible for patent matters. The awarding institute reserves the right to monitor awardee activity in this area to ascertain if patents or patent applications on mutagenesis protocols, cell lines, vectors, or other patentable subject matter are adversely affecting the goals of this PA. Principles and guidelines for recipients of NIH research awards on obtaining and disseminating biomedical research resources can be found at http://www.nih.gov/od/ott/RTguide_final.htm. WHERE TO SEND INQUIRIES We encourage inquiries concerning this PA and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into two areas: scientific or research, and financial or grants management issues: o Direct your questions about scientific and research issues to: Dr. Jonathan Pollock National Institute on Drug Abuse 6001 Executive Boulevard, Room 4282, MSC 9555 Bethesda, MD 20892-9555 Telephone: (301) 443-6300 Email: jpollock@mail.nih.gov Dr. Bradley C. Wise National Institute on Aging 7201 Wisconsin Avenue, Suite 3C307 MSC 9205 Bethesda, MD 20892-9205 Telephone: (301) 496-9350 FAX: (301) 496-1494 Email: wiseb@nia.nih.gov Dr. Lisa A. Neuhold National Institute on Alcohol Abuse and Alcoholism 6000 Executive Boulevard, Suite 402, MSC 7003 Bethesda, MD 20892-7003 Telephone: (301) 594-6228 Fax: (301) 594-0673 Email: Lneuhold@willco.niaaa.nih.gov Dr. Lynn Luethke National Institute on Deafness and Other Communication Disorders 6120 Executive Boulevard, MSC 7180 Bethesda, MD 20892-7180 Telephone: 301-402-3458 Email: luethkel@mail.nih.gov Dr. Philip Smith National Institute of Diabetes and Digestive and Kidney Diseases 2 Democracy Plaza Bethesda, MD 20892 Telephone: 301-594-8816 Email: SmithP@ep.niddk.nih.gov Dr. Michael D. Oberdorfer National Eye Institute 6120 Executive Boulevard Bethesda, MD 20892 Telephone: 301-451-2020 Email: mdo@eps.nei.nih.gov Dr. Michael F. Huerta National Institute of Mental Health 6001 Executive Boulevard, Room 7202, MSC 9645 Rockville, MD 20852-9645 Telephone: (301) 443-3563 Fax: (301) 443-1731 Email: mhuerta@helix.nih.gov Dr. Laura A. Mamounas National Institute of Neurological Disorders and Stroke (NINDS) Neuroscience Center, Room 2206, MSC 9525 6001 Executive Boulevard, MSC 9525 Bethesda, MD 20892-9525 (courier: Rockville, MD 20852-9525) Telephone: (301) 496-1447 Fax: (301) 480-1080 Email: mamounas@ninds.nih.gov Dr. Mary Lou Oster-Granite Health Scientist Administrator Mental Retardation and Developmental Disabilities Branch Center for Research for Mothers and Children 6100 Executive Boulevard, Room 4B09D, MSC 7510 National Institute of Child Health and Human Development Bethesda, MD 20892-7510 Telephone: (301) 435-6866 Fax: (301) 496-3791 Email: mo96o@nih.gov o Direct your questions about financial or grants management matters to: Gary Fleming, J.D., M.A. Grants Management Branch Office of Planning and Resource Management National Institute on Drug Abuse 6001 Executive Boulevard, Room 3131, MSC 9541 Bethesda, MD 20892-9541 Phone: (301) 443-6710 Fax: (301) 594-6847 Email: gf6s@nih.gov Ms. Linda Whipp Grants and Contracts Management Office National Institute on Aging 7201 Wisconsin Avenue, Suite 2N212, MSC 9205 Bethesda, MD 20892-9205 Telephone: (301) 496-1472 FAX: (301) 402-3672 Email: WhippL@nia.nih.gov Ms. Judy Simons Grants Management Branch National Institute on Alcohol Abuse and Alcoholism 6000 Executive Boulevard, Suite 504, MSC 7003 Bethesda, MD 20892-7003 Telephone: (301)-443-4704 FAX: (301)-443-3891 Email: jsimons@willco.niaaa.nih.gov Ms. Sara Stone Grants Management Branch National Institute on Deafness and Other Communication Disorders Executive Plaza South, Room 400B 6120 Executive Boulevard, MSC-7180 Bethesda, MD 20892-7180 Rockville, MD 20852 (express mail) Telephone: (301) 402-0909 FAX: (301) 402-1758 Email: stones@nidcd.nih.gov Ms. Kieran Kelley Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases 6707 Democracy Boulevard, Rm. 721 MSC 5460 Bethesda, MD 20892-5460 Telephone: (301) 594-0417 FAX: (301) 480-3504 E-mail: kk27g@nih.gov Mr. William Darby Grants Management Officer National Eye Institute/NIH Executive Plaza South, Suite 350 Bethesda, MD 20892-7164 Phone: (301) 496-5884 Fax: (301) 496-9997 Email: wwd@nei.nih.gov Ms. Carol Robinson Grants Management Branch National Institute of Mental Health 6001 Executive Boulevard, Room 6118 Bethesda, MD 20892 Telephone: (301) 443-3858 FAX: (301) 443-6885 Email: crobinso@mail.nih.gov Ms. Rebecca Claycamp Grants Management Branch National Institute of Neurological Disorders and Stroke 6001 Executive Boulevard, Room 3290 Bethesda, MD 20892 Telephone: 301-496-9231 Fax: 301-402-0219 Email: rc253d@nih.gov Ms. Mary E. Daley Grants Management Branch National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8A-17, MSC 7510 Bethesda, MD 20892-7510 Telephone: (301) 496-1305 FAX: (301) 402-0915 E-mail: md74u@nih.gov 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 Grants Info, Telephone (301) 710-0267, Email: GrantsInfo@nih.gov. SUPPLEMENTAL INSTRUCTIONS: The Research Plan for an application using the R21 mechanism need not include preliminary data. Figures are allowed in the appendix. APPLICATION RECEIPT DATES: Applications submitted in response to this program announcement will be accepted at the three dates listed at the beginning of this PA. 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 are capped at $100,000 for R21 mechanism. 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 the receipt dates listed at the top of this PA. 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 by the Center for Scientific Review 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 on 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) o DATA SHARING: The adequacy of the proposed plan to share data. o BUDGET: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. AWARD CRITERIA Criteria that will be used to make award decisions include: o Scientific merit (as determined by peer review) o Availability of funds o Programmatic priorities. REQUIRED FEDERAL CITATIONS MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD: Research components involving Phases I and II clinical trials must include provisions for assessment of patient eligibility and status, rigorous data management, quality assurance, and auditing procedures. In addition, it is NIH policy that all clinical trials require data and safety monitoring, with the method and degree of monitoring being commensurate with the risks (NIH Policy for Data Safety and Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html). 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. HIV/AIDS COUNSELING AND TESTING POLICY FOR THE NATIONAL INSTITUTE ON DRUG ABUSE: Researchers funded by NIDA who are conducting research in community outreach settings, clinical, hospital settings, or clinical laboratories and have ongoing contact with clients at risk for HIV infection, are strongly encouraged to provide HIV risk reduction education and counseling. HIV counseling should include offering HIV testing available on-site or by referral to other HIV testing services. Persons at risk for HIV infection including injecting drug users, crack cocaine users, and sexually active drug users and their sexual partners. For more information see http://grants.nih.gov/grants/guide/notice-files/NOT-DA-01-001.html NATIONAL ADVISORY COUNCIL ON DRUG ABUSE RECOMMENDED GUIDELINES FOR THE ADMINISTRATION OF DRUGS TO HUMAN SUBJECTS: The National Advisory Council on Drug Abuse recognizes the importance of research involving the administration of drugs to human subjects and has developed guidelines relevant to such research. Potential applicants are encouraged to obtain and review these recommendations of Council before submitting an application that will administer compounds to human subjects. The guidelines are available on NIDA's Home Page at www.nida.nih.gov under the Funding, or may be obtained by calling (301) 443-2755. 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 93.866, (NIA), 93.273 (NIAAA), 93.279 (NIDA), 93.173 (NIDCD), 93.847 (NIDDK), 93.867 (NEI), 93.242 (NIMH), 93.853 (NINDS), and 93.865 (NICHD), 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.
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NIH Funding Opportunities and Notices
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