THE HUMAN BRAIN PROJECT (NEUROINFORMATICS): PHASE I & PHASE II Release Date: August 5, 1999 (see replacement PAR-03-035) PA NUMBER: PAR-99-138 National Institute of Mental Health National Institute on Drug Abuse National Science Foundation National Institute on Aging National Institute on Child Health and Human Development National Institute on Deafness and Other Communication Disorders National Library of Medicine National Aeronautics and Space Administration Fogarty International Center Department of Energy National Institute on Alcohol Abuse and Alcoholism National Heart, Lung, and Blood Institute National Institute of Dental and Craniofacial Research National Cancer Institute National Institute of Neurological Disorders and Stroke Letter of Intent Receipt Dates: August 15, 1999; April 1, and October 1 in 2000 and beyond Application Receipt Dates: October 20, 1999; July 11, and January 11 in 2000 and beyond THIS PROGRAM ANNOUNCEMENT (PA) USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. IT INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS PA. This PA replaces PA-96-002, Human Brain Project: Phase I Feasibility Studies, which was published in the NIH Guide, Vol. 24, No. 25, October 6, 1995. PURPOSE The purpose of this initiative is to encourage and support investigator-initiated, Neuroinformatics research that will lead to new digital and electronic tools for all domains of neuroscience research reflecting normal and diseased states across the life span. Neuroinformatics combines neuroscience and informatics research to develop and apply advanced tools and approaches essential for a major advancement in understanding the structure and function of the brain. Research in Informatics includes databases, graphical interfaces, querying approaches, information retrieval, data visualization and manipulation, data integration through the development of integrated analytical tools, synthesis, and tools for electronic collaboration. In computational research, the focus is on development of structural, functional, integrative, and analytical models and simulations. The advanced information technologies resulting from this research will be put to wide use by the Neuroscience community. Therefore, the approaches and technologies solicited under this announcement should be generalizable, scalable, extensible, interoperable and use sophisticated powerful computational resources and integrated with significant neuroscience research at and across all levels of analysis of brain function. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS led national activity for setting priority areas. This Program Announcement (PA), THE HUMAN BRAIN PROJECT (NEUROINFORMATICS): PHASE I & PHASE II, is related to the priority area of brain disorders including mental health and mental disorders. Potential applicants may obtain a copy of "Healthy People 2000" at http://odphp.osophs.dhhs.gov/pubs/hp2000/ ELIGIBILITY REQUIREMENTS 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. Foreign institutions are not eligible for exploratory center (P20) or Program Project (P01) grants. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as principal investigators. MECHANISM OF SUPPORT Specific application instructions for R01s up to $250,000 have been modified to reflect "MODULAR GRANT" and "JUST-IN-TIME" streamlining efforts being examined by the NIH. Complete and detailed instructions and information on Modular Grant applications can be found at http://www.nih.gov/grants/funding/modular/modular.htm This program will use the research project grant (R01), exploratory center grant (P20), and the program project (P01) mechanisms for supporting neuroinformatics research. All P01 and P20 applications, as well as R01 applications exceeding $250,000 are to include full budgets and other support information. The National Institutes of Health (NIH) is expanding its use of the Modular Grant Application and Award. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total requested project period may not exceed five years and applicants should apply for the length of time appropriate for the work proposed, typically three to five years. This program is organized and supported by several Agencies and NIH Institutes and is coordinated by the National Institute of Mental Health (see INQUIRIES). The coordination takes place under the activities of the Federal Interagency Coordinating Committee of the Human Brain Project (FICC-HBP) and is chaired by the NIMH. An applicant planning to submit an application requesting $500,000 or more in direct costs for any year is advised that he or she must contact FICC-HBP program staff, listed under INQUIRIES, before submitting the application, i.e., as plans for the study are being developed. Furthermore, the applicant must obtain agreement from FICC-HBP staff that the Institute/Agency will accept the application for consideration for award. Finally, the applicant must identify, in a cover letter sent with the application, the staff member and Institute/Agency who agreed to accept assignment of the application. This policy requires an applicant to obtain agreement for acceptance of both any such application and any subsequent amendment. Refer to the NIH Guide for Grants and Contracts, March 20, 1998 (http://www.nih.gov/grants/guide/notice-files/not98-030.html). Since not all of the Federal organizations participating in this initiative support all of these mechanisms, it is important to contact program staff prior to preparing the application. GLOSSARY OF TERMS R01 Mechanism - The R01 mechanism will be used for research project grants, which will allow investigators to work on highly focused projects related to the integration of informatics research with brain, behavioral, and/or computational research. Applications may include requests for support of expenses for travel and per diem expenses to several laboratories to initiate or explore the possibility of setting up collaboration. It is essential that the scientific questions to be pursued and the unique contribution of each potential group member be explicitly stated. P01 and P20 Mechanism - These awards provide the opportunity for several investigators using different approaches to focus on a common problem. The grants will facilitate coordinated communication across disciplinary and geographic boundaries. This mechanism is intended specifically to support interdisciplinary research and feasibility studies. Not all Federal organizations will provide primary support for P01 and P20 grants. Therefore, prospective applicants should contact program staff (listed under INQUIRIES) prior to preparing an application for this mechanism. P01 and P20 Exploratory Grants are characterized by the synergy of their constituent projects. Each grant application must demonstrate the interrelationship of its constituent projects, and also indicate how the inclusion of each project will enhance the overall goals of the research. Principal Investigator: Each P01 and P20 Exploratory Grant will have a Principal Investigator with a demonstrated ability to organize, administer, and direct the grant. The Principal Investigator must commit at least 25 percent effort to the grant and be a Project Leader on one of the projects. Focus of research: The P01 and P20 Exploratory Grants will combine and integrate informatics with brain and/or behavioral research, including computational research, in an effort to develop novel approaches and technologies for accomplishing the neuroinformatics goals of the Human Brain Project. Group members: Each P01 and P20 Exploratory Grant will be composed of several laboratories, projects, and/or cores. It is expected that the Project Leaders of the constituent laboratories or projects will be regarded as leaders in their respective fields. Information sharing: In research funded by this mechanism, digital and electronic communication, especially via computer networks, will be established among different laboratories, projects and cores within a given P01 and P20 Exploratory Grant group. With evidence of adequate electronic communication channels given in the application, laboratories, projects, and cores participating in a given P01 and P20 Exploratory Grant group need not all be at the same geographic location. RESEARCH OBJECTIVES Background In 1989, the National Institute of Mental Health, the National Institute on Drug Abuse, and the National Science Foundation requested the Institute of Medicine to establish a Committee on a National Neural Circuitry Database. The Committee's charge was to consider the desirability, feasibility, and possible ways of implementing a family of resources, both electronic (e.g., computer networks) and digital (e.g., databases), for the enhancement of neuroscience research. After deliberations spanning almost 2 years and involving more than 150 scientific consultants, the Institute of Medicine endorsed the concept of mapping the brain and brain functions and issued several specific recommendations (Mapping the Brain and Its Functions: Integrating Enabling Technologies into Neuroscience Research, 1991, Institute of Medicine, National Academy Press). On April 2, 1993, the Human Brain Project was announced in Program Announcement PA-93-068, and published in the NIH Guide (Vol. 22, No. 13, April 2, 1993). Subsequently, a Notice and Addendum were published in the NIH Guide (August 27, 1993 and September 16, 1994, respectively) and a Revised Program Announcement was published in the NIH Guide (Vol. 24, No. 35, October 6, 1995). The Human Brain Project is a broadly based Federal research initiative that is sponsored by fifteen Federal organizations from four Federal agencies and coordinated by the National Institute of Mental Health. These sponsoring components are: the National Institutes of Health (National Institute of Mental Health, National Institute on Drug Abuse, National Institute on Aging, National Institute on Child Health and Human Development, National Institute on Deafness and Other Communication Disorders, National Library of Medicine, the National Heart, Lung, and Blood Institute, the National Institute of Dental and Craniofacial Research, the National Institute on Alcohol Abuse and Alcoholism, the National Institute of Neurological Disorders and Stroke, the Fogarty International Center, and the National Cancer Institute); the National Science Foundation (NSF); the National Aeronautics and Space Administration (NASA); and, the Department of Energy (DOE). Representatives from all of these organizations comprise the FICC-HBP. In addition, NASA will make available to Human Brain Project researchers its supercomputer and other resources of the Biocomputation Center. This initiative is being implemented in 3 Phases following the recommendation of the Institute of Medicine report. Phase I consists of research feasibility studies. Refinement of Phase I activities occurs in Phase II. Phase II support will be provided to build on accomplishments in Phase I and will consist of, but not limited to, expanded beta testing, further refinement of the newly developed tools, and the development of appropriate models and simulation capabilities. The tools resulting from this research and development will be made available to the scientific community at large in Phase III. Applications for Phase II are not required to have had Phase I support. The application for Phase II, however, must clearly demonstrate that equivalent neuroinformatics research has been accomplished on software or hardware which now requires Phase II activities and support. The research funded to date under the Human Brain Project has recently been assessed. This revised Program Announcement requests, on behalf of the participating Federal organizations, research grant applications for Phase I and II of the Human Brain Project (Neuroinformatics). This program announcement supersedes previous Program Announcements, Notices, and Addenda. Program Description Phase I of the Human Brain Project supports feasibility research on advanced technologies and novel ways to acquire, store, retrieve, manage, analyze, visualize, manipulate, integrate, synthesize, disseminate and share data about Neuroscience research, including tools for electronic collaboration. The Human Brain Project supports investigator-initiated projects that require both an Informatics research component and a Neuroscience (brain and/or behavioral) research component, with these two components well integrated with one another. Projects that focus only upon archival data are not appropriate for the Human Brain Project, but projects are encouraged to include legacy data in their informatics component. Phase II of the Human Brain Project extends and shares those products developed under Phase I with appropriate improvements, documentation and testing at multiple sites to move towards the distribution of the advanced technologies or tools to the wider community that will occur in Phase III. Phase II applications should include the necessary research components to: (1) build the elements necessary for the construction of maps and models (computational neuroscience); (2) ensure that databases in this area of research will be interoperable with other database resources; (3) incorporate the capability for the addition or linkage with legacy data; and (4) present a plan for the continued support of these capabilities. Objectives and Goals Neuroscientists understand the brain through experimental studies at multiple levels, throughout the life span and in multiple species, including humans in health and disease. Neuroscience data serves to identify the unique cell types, their elements and anatomical connections. Other data helps to elucidate the chemical substrates of function, which include tens of thousands of biochemical, molecular and genetic mechanisms that regulate and control brain structure and function to the level of behavior. Behavioral data encompass constructs as diverse as, but not limited to, attention, perception, learning, memory, cognition, emotion, and language. In addition, structural and functional information are measured and visualized during mental and behavioral activity through the use of the latest imaging technologies. Neuronal electrical activity is also studied to understand the biophysical events within cells, and to monitor neural activity in complicated neural networks. In order to integrate these diverse elements into an understanding of behavior and the functioning brain, the data from these multiple levels would benefit from analyses at the level of neural models. The greatest increment in knowledge about the brain has occurred within the last two decades due to intensive, rapid technological advances in molecular and cellular neurobiology, molecular genetics; brain imaging and other new technologies brought about through the computer revolution. The progressive amount of information being generated is exponentially incremental due to these and other approaches utilized by the estimated 50,000 neuroscientists working around the globe. These individual investigators, working in small groups on highly focused projects, publish their results monthly in one of approximately 200 scientific professional journals. The current challenge in Neuroscience is to integrate all of this information into a meaningful representative picture of how the brain develops, and functions, as well as malfunctions. The complexity and quantity of Neuroscience data create a compelling need to develop a global information management system for the neuroscience community. The potential to create an appropriate information management system has been amply demonstrated within the genomic community through the use of Bioinformatics. Compared to sequence data, data generated via Neuroscience research has many more levels of complexity, presenting both unique database requirements and constraints on interoperability. This effective demonstration in Bioinformatics and the continual advances within the fields of computer and informational sciences clearly point to the crucial need for the neuroscience community to fully embrace and engage in the science of INFORMATICS. The time is propitious for the effective use and integration of all levels of neuroscientific data through the shared global development of the new field of NEUROINFORMATICS. Neuroinformatics combines research in neuroscience and informatics and computation to develop and apply advanced tools and approaches needed for understanding the brain. This new interdisciplinary field, Neuroinformatics, is uniquely positioned at the intersection of medical science, biological science, neuroscience, behavioral science, physical science, computer science, mathematics and engineering. The synergy created by these combined approaches will result in a family of electronically distributed Neuroinformatics capabilities that will accelerate our ability to comprehend, heal and foster understanding of the normal development and function of the human brain. This unique capability will result in rapid scientific and technological progress to provide major medical, social and economic benefits. The brain is so complex that development of Neuroinformatics tools and strategies to adequately master its understanding will require full international cooperation and coordination. Scientific collaboration bridging brain, behavioral, computational research and informatics research (i.e., Neuroinformatics) promises to substantially advance all fields within their domain. Neuroinformatics research will accelerate the understanding of the brain by providing the necessary tools and means to fully understand the structural and functional entities required for successful function of the brain and the resultant appropriate behavior. These novel approaches include: databases, querying, data visualization, graphical interfaces and manipulation tools, and technologies for data synthesis and integration, modeling and electronic collaboration. Driven by the considerable demands made by the diversity, quantity, and complexity of data about the brain, neuroinformatics research will enable neuroscience research to expand the limits of knowledge in that field. Moreover, it is likely that solutions devised through neuroinformatics research will be generalizable to a wide range of scientific and other broad applications. Since each application appropriate to the Human Brain Project must include both an informatics research component and a brain and/or behavioral science research component, it is expected that each application will have substantial involvement of informatics and neuroscience researchers as principal investigators, other key personnel, or as very active consultants. It is expected that the multidisciplinary research components will be well integrated with each other, and will be true scientific collaborations, rather than parallel efforts. The research objectives that will have high priority are the following: INFORMATICS RESEARCH Research on databases, querying approaches, and information retrieval: The diversity of data types in neuroscience research will require unique databases and graphical interfaces that can accommodate varied data types (e.g., numerical, textual, graphic, image, time series). Also required are querying approaches that will allow varied databases to be accessed with a single query, and retrieval and analysis of different types of data into a common interoperable informational space. In addition, databases, querying and retrieval and integrated analytical tools will need to be extensible and easily reconfigurable to adjust to the rapidly changing domain of neuroscience research. Most database configurations have conformed to the needs of the financial or business community. Where as many of these approaches are adequate for various other fields of scientific research, they are not so for neuroscience research. For the latter purpose, new approaches and capabilities will need to be researched and created in order to deal with the dynamically changing data structures in Neuroscience. Research on data visualization and manipulation: Data about brain functions are extremely complex and highly interconnected. This high level of complexity requires novel approaches to manipulate, visualize, and analyze large interconnected data sets. These are necessary to be able to reliably represent and analyze the multiple dimensions across and within levels of analysis, and reflecting the complexity of neuroscience data that may later be cross validated. Both clinical and animal brain data require the development of interactive, multi-resolution capabilities for representation and visualization of tens to hundreds of gigabytes of imaging data at specified levels of resolution. Tools for electronic collaboration: The capacity to quickly assemble teams, independent of geographic location, to address specific scientific questions would greatly accelerate the pace of discovery. The creation of the capability or shared virtual reality space through the use of advanced forms of "groupware" with tools for data acquisition, display, interoperability, querying and manipulation would facilitate this goal. Research that builds bridges across existing informational tools and resources: The tools and approaches developed through the support of the Neuroinformatics field will prove to be most useful if and when they are combined in tandem with one another, and can access other databases and tools, such as those associated with the Human Genome Project and the Macromolecular Structure Database, etc. The informatics research component should be future-oriented and seek to exceed the current state-of-the-art. COMPUTATIONAL RESEARCH Research on data integration and synthesis, modeling and simulation environments: As scientific specialization increases, it become increasingly difficult to integrate and synthesize different types of data to comprehend complex brain structure and function relationships. Various models may serve as informational spaces by which experimentally obtained data of different types and sources can be better integrated and synthesized to derive new knowledge. Computational models are advantageous since they: require the user to make explicit their theory, identifying any inconsistencies or hidden assumptions; can help identify what data are missing, and guide the collections of data appropriate for testing a theory; provide a medium for the discovery of new principles of neural function, by supplementing intuitions that are limited by the complex, dynamical, and non-linear character of neural systems; and provide a clear and precise mechanism for communicating specific theories with other scientists. Research in this area is focused upon models of both physiological function and structure of the nervous system. All levels of models are appropriate, ranging from and between subcellular and molecular levels, to morphological, neuronal, and neural circuit levels, up to large-scale networks responsible for mediating normal behavior (e.g., cognition, emotions, etc.), and various brain disorders. Research in this area is heavily driven by the results of experimental studies and, reciprocally, provides a theoretical framework for the development of innovative, testable concepts that clarify current experimental observations that help to guide new experimental studies. Research to Develop Structural Models: Better models are needed at both the neuronal levels (e.g., three-dimensional structures of neuropil and dendritic trees, distributions of synaptic contacts, etc.), as well as at the level of the whole brain. For example, at the whole brain level, segmentation algorithms are needed for more accurate localization, atlasing and databasing of areas of activation identified in neuroimaging experiments. In addition, better morphometric models are needed for motion correction within subjects, for cross-subject comparisons (e.g., for studies of normal individual variability as well as group differences in patient populations), and for cross-modal registration of datasets (e.g., for Magnetic Resonance Imaging (MRI)-based localization of Event-Related Potentials (ERP) signals). Research to Develop Functional Models: Models are needed at all levels of function to improve our understanding of subcellular, cellular, circuit, and network level mechanisms. For example, the mechanisms underlying active dendritic conduction or coincidence detection are still poorly understood at the subcellular/cellular level, as are the mechanisms underlying temporal binding or sustained activity at the circuit/network level, and those underlying sequential behavior or instructed (versus associative) learning at the cognitive level. Research to Develop Integrative Models: Such models are needed to address two domains: (1) neural function, and (2) data analysis. With regard to neural function, new integrative models are needed to bridge between findings at multiple scales, by simultaneously addressing findings at each, and translating from one scale to another. For example, models are needed that can help us link our understanding at the level of gene expression to that at the level of receptor function and synaptic transmission; from that at the level of synaptic transmission to that at the level of circuit function; from circuit function to network activity; and from network activity to whole brain or its regional components that mediated cognitive, emotional and behavioral processes. Integrative models are also needed for more complete and effective analyses of data about the brain, generated by measurements made at different scales (e.g., direct neurophysiological recordings and functional neuroimaging), or using complementary modalities (e.g., spatially resolved positron emission tomography (PET) or functional Magnetic Resonance Imaging (fMRI) studies with temporally resolved (ERP) or magnetoencephalography (MEG) studies, or with MEG and fMRI studies). Modelers need to give careful consideration to the tools that they employ to construct their models. Simulators need to be developed capable of accommodating multiple scales, thereby facilitating the development of more integrative models. Also, attention must be given to the accessibility, interpretability, and interoperability of models that are generated, which includes documentation at all levels (code, interface, etc.). Improvements along these lines will facilitate the dissemination of models, which in turn would help promote interactions among modelers, and allow their models to realize full potential as valuable mechanisms for communication (e.g., with experimentalists, and for teaching). Finally, all models need to evolve through an iterative process of implementation, critical evaluation (against empirical data and/or competing models), and refinement. NEUROSCIENCE AND/OR BEHAVIORAL RESEARCH Research that includes experimental technologies and methodological approaches for the shared analyses, integration, and communication of neuroscience research. This would include, but is not limited to, data derived from multiple levels of biological organization, such as that at the levels of molecules, genes, cells and systems of cells. This includes those at all levels of behavioral constructs, including but not limited to attention, perception, learning, memory, cognition, emotion, and language. Research that integrates findings across these multiple levels and constructs is strongly encouraged. Research that includes structure-function relationships: This is needed at all levels of organization, from the level of the cell to that at the level of behavior. Research including cross-species comparisons: This is needed to address the issues and saliency of homology of structures, functions and behaviors as assessed across different species of research animal and humans. Research related to normal and abnormal brain development and behavioral function. This includes all mission-oriented research of the participating NIH Institutes and other participating Federal Agencies. Neuroinformatics Research Neuroinformatics research is expected to lead to advanced information technologies and approaches for the neuroscience community. In addition, the tools developed from this research will likely serve the entire neuroscience research community. In order to meet the long-term nature and breadth of this initiative, research projects with the following characteristics are sought: Generalizable: For example, algorithms for quantifying differences in 3-D reconstruction of data obtained from electron microscopy should generalize to volume data from confocal microscopy and MRI of whole brains. Research performed on sophisticated platforms: This initiative is a long-term program to support research and development of advanced information technologies for the neuroscience community. Computers that are sophisticated by current standards are likely to be widely available in five or ten years. Today's low-end machines are likely to be obsolete by the time that the tools currently being researched are later made available to the scientific community-at-large. Extensible, scalable and interoperable: Phase I research efforts will lead to tools and approaches intended for the scientific community-at-large, rather than an individual laboratory. In order to achieve this goal, it is important that issues of scalability and extensibility be addressed from the outset. Phase II will need to also focus on extensibility and scalability and, in addition, consider the importance of interoperability with other tools, databases and workstations. Designed to assess progress: Since research and development is ultimately intended to be of use not only to an individual laboratory, but to a wide range of laboratories, it is important that methods to assess progress towards achieving the objectives of this Neuroinformatics initiative in both Phase I and Phase II be carefully addressed. This includes the development and documentation of standards by which tools are to be tested for reliability and accuracy. Permanence and Maintenance: The lifetime value and use of hardware or software is a function of its broad utilization by the community. For this to occur, a plan must be presented in Phase II for the continued support of these capabilities. This plan can be developed from a variety of options; however, the plan must be viable and self-sustaining, and not be dependent upon support derived from Federal funding in its entirety. Each Human Brain Project supported will have, at the minimum, an informatics research component as well as a neuroscience research component. This initiative will provide support for any or each of these components. It may, however, also be carried out under already funded, on-going peer-reviewed research support. Each project will report the attainment of proposed specific aims through progress reports and the timely publication and dissemination of results, including aspects such as software, database designs, and source codes. It is strongly encouraged that researchers funded by different grants under the Human Brain Project will communicate, coordinate and collaborate across different Project grants. Supplemental funds may be competitively awarded to projects to support such interactions. A listing of investigators participating in Phase I and II is located at http://www.nimh.nih.gov/neuroinformatics/index.cfm and the types of data, software, or other information that is available from or through them will be shared among all grantees to minimize scientifically unnecessary duplication of effort in all Phases. Grantees are expected to participate in the Annual Spring Human Brain Project Meeting of Agencies and Grantees. These meetings will promote communication among different groups of investigators, and will be held in the Washington, D.C. area. NIH is interested in ensuring that the research resources developed through this Program Announcement 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. 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. Indeed, for inventions developed in its intramural program, NIH does file patent applications, in accord with a set of policies described at http://ott.od.nih.gov/phspat_policy.html. Grantees are encouraged to perfect copyright protection of software produced as a result of Human Brain Project funding. These should include prominent notification in the software and its documentation that the software is copyrighted. Notification could consist of the following: Copyright c [year] by [your name, the names of you and your colleagues, or the name of your institution] with funding from the Human Brain Project. This notification will identify the source of the software and help ensure that the software can be shared freely while protecting any commercial rights in it. In addition, grantees will be required to agree that they will provide the primary funding organization, upon its request and at a reasonable cost, a copy of any software produced under this Human Brain Project funding, with the understanding that the Federal organizations directly involved with this Project will have the right to use such software for internal research and archival purposes only, and will not permit its distribution beyond those organizations. Application components related to ethical, legal, and social issues pertinent to this initiative are encouraged. Also encouraged are components of applications that are designed to reach out to the public, academic, and/or commercial sectors to help educate and inform about the available opportunities provided by research and development in the neuroinformatics field. Availability of Computational Resources The choice of computational resources to be used in Human Brain Project research is entirely that of the applicant and the range of appropriate resources extends across the entire spectrum of computer technology. Nevertheless, some investigators may be interested in using, or collaborating with those using supercomputers, massively parallel computers, and other advanced technologies that may not be available at their institution. To facilitate such use and collaboration, the following information is provided. The NSF supports High Performance Computer Centers and Science and Technology Centers. Individuals considering applications for supercomputer use should contact these centers early in the application development process. Cornell Theory Center Linda Callahan 514 Engineering and Theory Center Building Ithaca, NY 14853-3801 Telephone: (607) 254-8610 Email: [email protected] National Center for Atmospheric Research, Scientific Computing Division Visitor/User Information P.O. Box 3000 Boulder, CO 80307 Telephone: (303) 497-1225 Email: [email protected] National Center for Supercomputing Applications Scott Lathrop 605 East Springfield Avenue Champaign, IL 61820-5518 Telephone: (217) 244-1099 Email: [email protected] Pittsburgh Supercomputing Center Robert B. Stock 4400 Fifth Avenue Pittsburgh, PA 15213 Telephone: (412) 268-4960 Email: [email protected] San Diego Supercomputer Center Mark Sheddon P.O. Box 85608 San Diego, CA 92186-9784 Telephone: (619) 534-5130 Email: [email protected] In addition, NASA will make available computational resources of the Biocomputation Center (BC) at Ames Research Center, Moffett Field, California. These resources include computer-controlled transmission electron microscopy for semiautomatic 3-D reconstruction of neural tissue, virtual environments, high-performance workstations, supercomputers, and massively parallel computers. A scientist interested in using the BC as part of their Human Brain Project must submit a written request for facility use to the BC Director prior to submitting an application to the Public Health Service. This request must state the objectives of the intended work and the approaches to be used. This request must also provide enough information to allow BC staff to assess whether or not the intended use is within the capability of the BC. In addition, this request must provide information necessary to allow BC staff to determine the amount of time the proposed work will require. The BC staff will provide the requesting scientist an itemized estimate of the costs for BC resources needed to achieve the stated objectives. The scientist will use this estimate as part of the budget justification in the Public Health Service application for funds to support the Human Brain Project research. Requests for BC use are to be sent to: Dr. Muriel Ross Director Biocomputation Center MS 261-2 Ames Research Center Moffett Field, CA 94035-1000 INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided 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 "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Vol. 23, No. 11, March 18, 1994 available on the web at the following URL address: http://www.nih.gov/grants/guide/1994/94.03.18/notice-nih-guideline008.html INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of NIH that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. This policy applies to all initial (Type 1) applications submitted for receipt dates after October 1, 1998. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects" that was published in the NIH Guide for Grants and Contracts, March 6, 1998, and is available at the following URL address: http://www.nih.gov/grants/funding/children/children.htm 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. LETTER OF INTENT Potential applicants are encouraged to contact the appropriate program official(s) listed under INQUIRIES and submit a letter of intent. The letter should include a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, names of other key personnel, and participating institutions, and the number and title of the program announcement 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 is helpful in planning for the review of applications. The letter is to be submitted to Dr. Stephen H. Koslow at the address listed below. APPLICATION PROCEDURES 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 Modular Grant applications will request direct costs in $25,000 modules, up to a total direct cost request of $250,000 per year. (R01 applications that request more than $250,000 direct costs in any year must follow the traditional PHS 398 application instructions.) 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 $250,000) 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 http://www.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 key 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: http://www.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. Applications are to be submitted on the grant application form PHS 398 (rev. 4/98) and will be accepted only at the application receipt dates listed below. Application kits are available at most institutional offices of sponsored research and may be obtained 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: [email protected]. The PHS 398 application kit is also available on the Internet at http://www.nih.gov/grants/forms.htm. Follow the PHS 398 instructions for "Preparing Your Application" with modifications and additions as described in the sections below. Addition information describing the purpose, eligibility requirements and application instructions for several types of NIH awards is also available at http://www.nih.gov/grants/funding/funding_program.htm Applicants planning to submit an investigator-initiated new (type 1), competing continuation (type 2), competing supplement, or any amended/revised version of the preceding grant application types requesting $500,000 or more in direct costs for any year are advised that he or she must contact the Institute, Center, or Agency (ICA) program staff before submitting the application, i.e., as plans for the study are being developed. Furthermore, the application must obtain agreement from the ICA staff that the ICA will accept the application for consideration for award. Finally, the applicant must identify, in a cover letter sent with the application, the staff member and Institute, Center or Agency who agreed to accept assignment of the application. This policy requires an applicant to obtain agreement for acceptance of both any such application and any such subsequent amendment. Refer to the NIH Guide for Grants and Contracts, March 20, 1998 at (http://www.nih.gov/grants/guide/notice-files/not98-030.html). Each application must clearly articulate the manner in which the informatics research components relate to, and are well integrated with, the brain and/or behavioral research component(s). Because Phase I of the Human Brain Project research supports feasibility studies, each application must describe specific mechanisms proposed to evaluate the success of the research in terms of feasibility. R01 Mechanism: For the R01 mechanism, applicants must follow the instructions provided in grant application form PHS 398 (rev. 4/98). Funds to support travel to the two-day Annual Spring Meeting of Human Brain Project Agencies and Grantees should be included in the budget for the principal investigator and up to one additional key member of the research team. P01 and P20 Mechanism: The application must describe the specific research hypotheses to be tested and how they relate to the overall research issue to be addressed. In applications for the P20 mechanism, funds to support travel to the two-day Annual Spring Human Brain Project Meeting of Agencies and Grantees should be included in the budget for the principal investigator (the director of the grant), the director of each subproject and core, and up to one additional key member from the P01 or P20 research team. For the P01 and P20 applications only, the Research Plan Section of PHS Form 398 (Specific Aims, Background and Significance, Progress Report/Preliminary Studies, and Research Design and Methods) should be replaced by the following: General Description of the Overall Project (Not to exceed 10 pages): The applicant must provide an overview of the proposed project and its central theme and goals, describe the general objectives, and explain the proposed contribution of each of the individual projects and cores towards achieving these objectives. Furthermore, the administrative arrangements and support necessary to effect the research should be carefully described in the application. In particular, when more than one institutional site is involved a detailed description and supporting documentation for the administrative arrangements must be included. Detailed information on collaborations, recruitment, facilities, and resources must also be provided. Individual Projects (Not to exceed 15 pages for any one project): The applicant must describe the major objectives and goals of each individual project and its relationship to the effort of the entire group of constituent projects. Where appropriate, an Information Model should be presented to describe, define and conceptualize the problem domain. In addition, detailed descriptions should be provided on the following: Research Plan: The questions to be addressed and the hypotheses to be tested by the proposed research should be highly focused and fully explained. Full discussion is required on the status of current research efforts, the limitations of existing approaches, and how the research questions posed relate to the objectives of the Human Brain Project. In addition, the integrative relationship between the brain and/or behavioral research component and the informatics research component components should be made explicit, as should the novelty of the informatics research component. Experimental Plan: The description of the experimental design should provide the specific strategies proposed to accomplish the specific aims of the project in clear detail and should include a discussion of the innovative aspects of the approach. New methodology and its advantage over existing methodologies should be fully described. The feasibility of the proposed experiments, the potential pitfalls, alternative approaches, means of assessing success of research to meet the objectives of the Phase I or Phase II of the project, and relevance to the goals of the project as a whole should be fully discussed. The methods to be used should be cited and referenced. Cores (Not to exceed 5 pages for any one core): If cores are required, the applicant must describe how each core will contribute to the goals of the overall project as well as how each individual project will draw upon a particular core. The description of each core should clearly indicate the facilities, resources, services and professional skills that the facility will provide. Moreover, clearly described information must be provided about how the collective operation of the cores will be effected in a coherent manner. Operational Plan: A description of the resources (local and collaborative) and working and logistical arrangements required to implement the research plan should be fully elaborated. If a project includes a clinical component, attention should be devoted to a description of the clinical populations and tissue resources. A distinction must be made between those resources that are already in place (including staff) versus those resources that must be added to carry out the proposed research. Permanence and Maintenance Plan: The lifetime value and use of hardware or software is a function of its broad utilization by the community. For this to occur, a plan must be presented in Phase II for the continued support of these capabilities. This plan can be developed from a variety of options; however, the plan must be viable and self-sustaining, and not be dependent upon support derived from Federal funding in its entirety. Evaluation Plan: A description must be provided specifying the approaches that will be taken to evaluate the success of the new neuroinformatics capability and its utility to neuroscientists. Applications for P01 or P20 grant mechanisms will not be accepted from organizations outside of the United States. The title and number of the program announcement must be typed on line 2 of the face page of the application form and the YES box must be marked. In addition Phase I or Phase II should be indicated. 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 time of submission, two additional copies of the application (including appendices) must also be sent under separate cover to the chair of the FICC- HBP: Stephen H. Koslow, Ph.D. Director, Office on Neuroinformatics National Institute of Mental Health 6001 Executive Boulevard, Room 6167 MSC 9613 Bethesda, MD 20892-9613 Rockville, MD 20852 (for express/courier service) Telephone: (301) 443-1815 FAX: (301) 443-1867 Email: [email protected] It is important to send these copies at the same time that the original and three copies are sent to CSR; otherwise, it cannot be guaranteed that the applications will be reviewed in competition with other applications received in response to this Program Announcement. Schedule 1999 Calendar Year 2000 & Beyond Letter of Intent Receipt Date: Aug 15, 1999 Apr 1, 2000 Oct 1, 2000 Application Receipt Date: Oct 20, 1999 Jul 11, 2000 Jan 11, 2000 Administrative Review: Oct 1999 Jul 2000 Jan 2001 Scientific Review: Feb/Mar 2000 Sep/Oct 2000 Mar/Apr 2001 Advisory Council Review: May/Jun 2000 Jan/Feb 2001 May/Jun 2001 Earliest Starting Date: Jul 2000 Mar 2001 Jul 2001 REVIEW CONSIDERATIONS Applications that are complete will be evaluated for scientific and technical merit by an appropriate peer review group convened by one of the Federal organizations sponsoring the "Human Brain Project" program. As part of the initial merit review, all applications will 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 applications under review, will be discussed, and assigned a priority score. Subsequent processing of the application will follow the procedures of the respective agency, institute and/or center to which it has been assigned. For applications assigned to a Public Health Service (PHS) institute or center, the application will receive further review by the appropriate National Advisory Council. All successful projects will be identified as "A Unit of the NIH/NSF/NASA/DOE Human Brain Project/Neuroinformatics" program. REVIEW CRITERIA The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments reviewers will be asked to discuss the following aspects of the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, 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? Will the proposed project(s) to accomplish the goals of this PA? (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 initial review group will also examine: the appropriateness of proposed project budget and duration; the adequacy of plans to include both genders, minorities and their subgroups, and children as appropriate for the scientific goals of the research and plans for the recruitment and retention of subjects; the provisions for the protection of human and animal subjects; and the safety of the research environment. The research project (R01) grant funding mechanism will be used under this program announcement to allow investigators to work on highly focused projects related to the integration of informatics research with brain, behavioral, and/or computational research. In contrast, the program project research grant (P01) and the exploratory center (P20) grant funding mechanism will provide the opportunity for several investigators using different approaches to focus on a common problem, and to facilitate coordinated communication across disciplinary and geographic boundaries. Therefore, the initial review group needs to adequately consider differences in the respective application requirements and their major section components when applying these 5 review criteria. Phase I applications are to support feasibility research on advanced technologies and novel approaches to create and render data about the brain and behavior more generalizable, scalable, extensible, and interoperable. Hence, the peer review of these applications requires a full assessment of the feasibility of these applications to accomplish their specific major stated objectives. For HBP Phase II applications, both those submitted as new applications and those representing previously funded competitive renewal (type 2) grants under the HBP program, a detailed "Progress Report" should be provided in support of the proposed project. This report, which will be considered as an important part of the initial review, should include detail about the major accomplishments, to date, and currently described plans for further improvement, documentation, and multi-site testing of advanced technologies and tools for shared distribution across the wider community of neuroscientists and Neuroinformaticians. Concerning the latter, relevant information should be included about the validation, expanded beta testing, and further refinement of newly developed tools; the development of appropriate models and simulation capabilities; the interoperability of information sharing; and a careful evaluation of these products for general distribution among the neuroscience and neuroinformatics research communities. The operational, maintenance and evaluation plans should be realistic and deal with relevant issues. These issues should be considered both in terms of their being state-of-the-art, yet also with perspective toward future developments. AWARD CRITERIA Applications will compete for available funds with all other recommended approved applications. The following will be considered in making funding decisions: Quality of the proposed project as determined by peer review, availability of funds, and program priority. POST-AWARD MANAGEMENT The FICC-HBP committee maintains a WWW site containing information about this and related programs and activities. Each funded grant application will be listed and briefly described and hotlinks provided to connect interested parties to the grantees web site that should provide greater details about research activities and the state and availability of research tools and products. In addition, grantees are expected to participate in the Annual Spring Human Brain Project Meetings of Agencies and Grantees. These meetings will promote communications among different groups of investigators, who are involved in research, curricula development, and career development and/or other cross-training activities in Neuroinformatics. Therefore, budget requests should include travel funds for the principal investigator and others to meet annually in the metropolitan Washington, D.C. area for this purpose. INQUIRIES Inquiries are encouraged. The opportunity to clarify any issues or questions regarding an application from potential applicants is welcome. The following FICC-HBP representatives from each of the participating agencies, institutes and center can be contacted for further information or clarification. Potential applicants are strongly encouraged to contact the agency or institute representative to discuss their plans prior to preparing an application. General programmatic inquiries regarding the Human Brain Project/ Neuroinformatics program may be directed to the chair of the coordinating committee: Stephen H. Koslow, Ph.D. Office on Neuroinformatics National Institute of Mental Health 6001 Executive Boulevard, Room 6167, MSC 9613 Bethesda, MD 20892-9613 Telephone: (301) 443-1815 Fax: (301) 443-1867 Email: [email protected] Inquiries regarding fiscal matters may be directed to: Diana S. Trunnell Grants Management Branch National Institute of Mental Health 6001 Executive Boulevard, Room 6120, MSC 9605 Bethesda, MD 20892-9605 Telephone: (301) 443-3065 FAX: (301) 443-6885 Email: [email protected] Questions regarding scientific issues, management issues, issues on cores related to participating Institutes and Centers (ICs), and fiscal matters should be directed to the programmatic and fiscal contacts for each participating IC. A current list of the contacts for the participating ICs may be found at: http://www.nimh.nih.gov/neuroinformatics/agencycontacts.cfm. AUTHORITY AND REGULATIONS This program is described in the Catalogue of Federal Domestic Assistance Nos. 93.242 (NIMH), 93.279 (NIDA), 47.074 (NSF), 93.866 (NIA), 93.865 (NICHD), 93.173 (NIDCD), 93.879 (NLM), 93.934 (FIC), 81.049 (DOE), 93.273 (NIAAA), 93.838 (NHLBI), 93.121 (NIDCR), 93.395 (NCI), and 93.854 (NINDS). Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal regulations 42 CFR 52 and 45 CFR part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 as implemented through Department of Health and Human Services regulations at 45 CFR part 100 or Health Systems Agency Review. Awards by PHS agencies will be administered under PHS grants policy as stated in the NIH Grants Policy Statement (October 1, 1998). PHS strongly encourages all grant and contract recipients to provide a smoke- free workplace and promote the nonuse 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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