MOUSE BRAIN ATLAS FOR FUNCTIONAL GENOMICS Release Date: February 3, 1999 PA NUMBER: PAS-99-060 P.T. National Institute of Mental Health National Institute of Neurological Disorders and Stroke National Institute on Aging National Institute on Alcohol Abuse and Alcoholism National Institute on Drug Abuse National Eye Institute National Institute of Child Health and Human Development National Institute on Deafness and Other Communication Disorders Letter of Intent Receipt Date: April 19 Application Receipt Date: May 19 PURPOSE The Brain Molecular Anatomy Project (BMAP) is a multi-institute initiative that supports research on the genomics of the nervous system, with initial efforts focussing on the discovery of new genes and the study of gene expression patterns in mouse and human brains. This initiative will provide the capability to quantify and track the expression of tens of thousands of genes in space and time, and will generate enormous amounts of such data. Ongoing efforts to localize genes to multiple anatomic regions of the mouse nervous system and to identify which genes are expressed in specific regions require a quantitative and highly detailed anatomic map of the mouse nervous system. Furthermore, such a map is essential to realize the full potential of data collected in BMAP-supported projects. In recognition of these needs, this Program Announcement (PA) solicits grant applications to research and develop a digital multidimensional atlas that ultimately will serve as a platform to organize and integrate genomic data obtained from the mouse nervous system. Early efforts are likely to primarily focus on atlases of the brain, due to the technologies available and its relative geometric simplicity, but it is envisioned that atlases and related tools would ultimately accommodate data from the entire central nervous system, the peripheral nervous system and special sense organs (herein, collectively referred to as the "nervous system"). This atlas will likely comprise an array of interoperating informatics tools and approaches for handling gene expression data obtained from the mouse nervous system. It is not expected that any one research group would develop all of the tools needed or atlases of all parts of the nervous system. The algorithms and their implementations resulting from grants funded under this PA must be extensible and scalable, and, ideally, should be modifiable to accommodate genomic data obtained from the human nervous system. It is thus important that informatics tools and approaches supported by this initiative are designed to allow for articulation with other such tools and approaches. Given the nature of the research and development solicited under this PA, hypothesis-driven as well as design-driven efforts are considered appropriate. The research and development supported under this PA will be iterative, with early versions providing basic functions that would be elaborated upon in subsequent versions. The intention is to introduce early versions of these tools to the research community generating gene expression data and to develop an atlas of the nervous system of the C57BL6/J strain of mouse. Ultimately, it is expected that uses of the tools and approaches developed under this PA will extend beyond functional genomics. Atlases, informatics tools, and other materials and information generated in projects funded under this PA will be made widely available to the scientific community. 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), "MOUSE BRAIN ATLAS FOR FUNCTIONAL GENOMICS", is related to various priority area relevant to each sponsoring institute, including Mental Health and Mental Disorders, Alcohol and Other Drugs/Substance Abuse, Heart Disease and Stroke, Cancer, and Maternal and Infant Health. Potential applicants may obtain a copy of "Healthy People 2000" at http://www.crisny.org/health/us/health7.html. 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. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORT This PA will use the National Institutes of Health (NIH) research project grant (R01) mechanism. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for a grant application submitted in response to this PA may not exceed 5 years. Because the nature and scope of the research proposed in response to this PA may vary, it is anticipated that the sizes of awards will vary as well. It is expected that while some grants will support unique efforts, other grants may provide support that would allow investigators to build upon ongoing, funded informatics research and development, such as that supported by informatics initiatives associated with the Digital Library Initiative, the Human Genome Project, or Human Brain Project. Competing supplements will be considered from applicants already funded by participating NIH Institutes and Centers to carry out similar or related informatics research and development under this PA. Investigators who are considering submitting a competing supplement application are strongly encouraged to contact program staff listed under INQUIRIES to obtain specific information. This PA will have one a once a year special receipt date, new, amended, competing supplements and competing applications will be received on that date each year. 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 Institute program staff before submitting the application, i.e., as plans for the study are being developed. Furthermore, the applicant must obtain agreement from Institute staff that the Institute 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 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. Applicants who are uncertain regarding which Institute or Center to contact should call the Referral Office, Center for Scientific Review. Refer to the NIH Guide for Grants and Contracts, March 20, 1998 which is located at http://www.nih.gov/grants/guide/notice-files/not98-030.html. FUNDS AVAILABLE Under this PA, it is estimated that approximately $2,000,000 will be available to support about four to seven grants for which applications are received under the first receipt date. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although the financial plans of the sponsoring NIH Institutes include these proposed levels of support for the first round of applications, awards made under this PA are contingent upon the availability of funds for this purpose. Funding of applications that are submitted under this PA at subsequent receipt dates will compete with all other unsolicited grant applications for funding. RESEARCH OBJECTIVES Background The Brain Molecular Anatomy Project (BMAP) is a multi-institute NIH initiative which supports research on the genomics of the nervous system, with initial efforts focussing on the discovery of new genes and the study of gene expression patterns in mouse and human brains. This initiative will provide the capability to quantify and track the expression of tens of thousands of genes in space and time, and will generate enormous amounts of such data. The value of these data will be derived from understanding not only the spatial and temporal expression patterns of individual genes, but also, how these patterns relate to expression patterns of other genes and to events such as changes in behavioral state, onset of disease, and response to drugs. The kinds of data generated by research funded under BMAP will include: 1) localization of where particular genes are expressed in the nervous system, 2) changes in gene expression patterns as particular genes are expressed through development and across the lifespan, after onset of disease, with exposure to drugs, with changes in behavioral state, etc., and 3) the relationship of expression of a particular gene to expression patterns of other specific genes or gene products. These domains of data will be most meaningful when considered not just alone, but in relation to one another. The capability to fully integrate such data for tens of thousands of genes presents tremendous challenges for informatics research and development, and will ultimately require very powerful and sophisticated tools and approaches. Ongoing efforts to localize genes to multiple anatomic regions of the mouse nervous system via in situ hybridization studies, and to identify which unique transcripts are expressed in specific regions, require a quantitative, precise and highly detailed anatomic map of the mouse nervous system that is developed using standardized anatomic landmarks. Such a map is essential to realize the full potential of data ultimately collected in BMAP-supported projects. This PA solicits grant applications to research and develop such a digital multidimensional atlas that ultimately will serve as a platform to organize and integrate genomic data obtained from the mouse nervous system. As demonstrated in the bioinformatics efforts associated with the Human Genome Project and the neuroinformatics research supported by the Human Brain Project, informatics is increasingly important and widely used in modern biology and biomedicine. The reasons for this derive from the convergence of three factors. First, the amount, diversity, and complexity of biological and biomedical data are enormous, and can be neither fully integrated nor appreciated without the use of informatics solutions. Second, informatics tools are rapidly becoming more powerful and, at the same time, easier to use. Third, the use of informatics tools and approaches, such as the World Wide Web, personal digital assistants, Email, etc., have become a commonly accepted way to interact with data and people, both inside and outside of the laboratory. Consequently, projects supported under this PA are expected to develop a set of informatics tools to support a wide range of uses of the atlas, and to specifically facilitate the integration of anatomic and genomic/genetic data in BMAP. Research Topics Many informatics tools and approaches are needed to make optimal use of gene expression data. The focus of this PA, however, is limited and will focus exclusively on a digital, volumetric atlas and associated tools that will serve as a framework for storing, presenting and analyzing a variety of data in four dimensions. The atlas will also serve as a point of articulation with related informatics technologies and resources, including bibliographic resources, and those associated with the Human Genome Project and the Human Brain Project. A fundamental capability for such an atlas to be useful is to translate data from histological sections into the atlas itself. If invertible, this translation would allow for data to be entered into the atlas for comparison with other data, and retrieved to be re-analyzed, if needed. Translation into and out of the atlas might use algorithms for deforming the digitized images of the sections containing the gene expression patterns, and fitting them into the most appropriate three dimensional space in a time-defined atlas. In addition, tools for quantifying the deformation and assessing variance from other sections, other groups of sections, or even other atlases, would allow for the probabilistic analysis of the distribution of gene expression, and other, patterns in time and space. Another essential feature of such an atlas is the capability to relate gene expression data to architectonic features, such as the borders of a subcortical nucleus or cortical area. This might be achieved by entering images of sections with gene expression data along with images from adjacent sections stained, for example, for Nissl substance. Using warping tools, the architectonic borders could be related to the patterns of gene expression on the adjacent section, and these relationships could be carried into the atlas itself. Similarly, architectonic, connectional or other types of data could be incorporated from other laboratories or atlases (with appropriate permissions and clearances). In this way, it would be possible to compare gene expression data with a variety of interpretations of architectonic and other data. Search functions and data mining approaches will serve to retrieve data, enhance the appreciation of the significance of those data, and reveal information that might not have been otherwise apparent. Data analysis and visualization tools important in this atlas include the means to present and compare multiple datasets. For example, visualizing where in the brain a particular gene is expressed at a given time point, or comparing the expression of multiple gene families in a particular brain structure. Additional features that would be relevant to a digital atlas include algorithms for analyzing signal-to-noise ratios in primary data, filtering and thresholding primary data, and a means to annotate the data, such as fields to describe the experimental conditions and other aspects of the manner in which the data were obtained, bibliographic links, links to other databases, etc. The informatics framework to be developed is expected to eventually be integrated with existing informatics tools by which investigators can order on-line specific clones from BMAP-supported repositories. Finally, as the intention is to make the technologies developed under this PA available to a wide research community, not only should these be user-friendly and documented, but should be largely platform-independent. Research Characteristics It is expected that grants funded under this PA will proceed iteratively, with early prototypes providing some rudimentary functions within a year of funding initiation. These prototypes would be made available to the BMAP research community, and would become increasingly sophisticated, and added to, in subsequent versions. In each application, the features and functions of early versions (i.e., those to be accomplished within the first year of funding) should be described, as well as those expected in later versions. An example of how a particular project might elaborate over time would be the development of a digital, volumetric atlas which starts as a volume dataset (e.g., obtained from magnetic resonance imaging) of an individual animal, and is added to over time with datasets from other animals of varying ages, strains, sizes, etc. In this example, a simple spatial atlas of a particular animal at a particular time in the lifespan would provide the starting point (similar to published brain atlases available now). Subsequent versions of such an atlas could be used in a probabilistic fashion, and could accommodate very accurately data derived at different time points, from different strains, etc. Another example of iterative elaboration would be starting with a volume dataset of a particular animal from a particular modality (e.g., magnetic resonance imaging), with additional datasets from images of that same brain from other modalities being brought into the atlas (e.g., images of Nissl- stained sections of the same brain warped into the three dimensional atlas based on the magnetic resonance image). Again, the early version would be useful for basic data management, but later versions would add functions and power, without making obsolete data entered in earlier versions. Since there will be many opportunities for future research and development of BMAP-related informatics, and since no one investigator would be able to address all of them, investigators are strongly encouraged to use open architectures, shareable code, or other strategies that will allow others to develop tools and approaches which are interoperable. In addition, it is expected that investigators funded under this PA would communicate frequently with others funded under this PA to minimize unnecessary duplication of effort and to optimize the use of resources. Investigators will be expected to attend two meetings each year of researchers funded under this PA. These meetings will be in the Washington, D.C. area, and applicants are advised to budget for two such trips for two individuals each year. Moreover, after funding begins, collaborative efforts among different projects will be strongly encouraged and will be considered for supplemental support. It is expected that BMAP research will extend from mouse to human, and it is important that, to the extent possible, informatics solutions arrived at in the research funded under this PA be generalizable to accommodate such variety. While some features of a digital volumetric atlas will remain important, the need for features not currently envisioned will likely arise as understanding of gene expression develops and as new technologies become available and widely used. Therefore, it is important that tools and approaches developed under this PA be extensible. Similarly, as the amount of data, and the number of laboratories using these new technologies increase, it is essential that the efforts supported under this PA are scalable to these new levels of use. Finally, with the need to develop early, workable informatics solutions, continual evaluation of progress is key, and the manner in which progress will be assessed should be detailed in the grant application. Validity and reliability of informatics approaches to be developed should be carefully evaluated in a scientifically valid, objective, and as quantitative way as possible. SPECIAL REQUIREMENTS Dissemination of Research Resources The sharing of materials, data, and software in a timely manner has been an essential element in the rapid progress that has been made in the genetic analysis of human diseases. PHS policy requires that investigators make unique research resources readily available for research purposes to qualified individuals within the scientific community when they have been published (PHS Grants Policy Statement in the July 12, 1996 issue of the NIH Guide to Grants and Contracts). Research materials and results produced in projects funded by this RFA will be distributed to scientific investigators conducting in the wider research community, and will augment existing resources. 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 patent applications for a large number of atlases and informatics tools 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. 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. To address the joint interests of the government in the availability of, and access to, the results of publicly funded research and in the opportunity for economic development based on these results, NIH requires applicants who respond to this PA to develop and 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, including but not limited to, nervous system atlases and related informatics tools. It is expected that the investigator"s data sharing plan will include the following elements: (1) establishment of a comprehensive description of the atlas and related informatics tools developed in the project, (2) development of documentation to assure reproducible use by other laboratories, (3) elaboration of mechanisms to promote the wide distribution of resources to investigators in the scientific community, including information needed by others to add interoperable, or at least compatible, capabilities, and (4) a distribution timetable. The initial review group will comment on the proposed plan for sharing and data access. The plan will be considered part of the scientific methodology for carrying out the research and, as such, the adequacy of the plan will be considered by NIH program staff in determining whether the grant shall be awarded. The sharing plan as approved, after negotiation with the applicant when necessary, will be a condition of the award. Evaluation of renewal applications will include assessment of the effectiveness of research resource release. It is expected that this plan includes all elements of the guidelines developed by the NIH and the Department of Energy (DOE) to address the special needs of genome research. These guidelines call for material and information from genome research to be made available within six months of the time the data or materials are collected, and are available on the Web at http://www.nhgri.nih.gov/Grant_info/Funding/Statements/data_release.html. Adherence with this time frame is highly desirable. More rapid sharing is encouraged. Requests for exemptions or extensions will require compelling justification and will be fully evaluated through peer review and by program staff. Applicants are also reminded that the grantee institution is required to disclose each subject invention to the Federal Agency providing research funds within two months after the inventor discloses it in writing to grantee institution personnel responsible for patent matters. The awarding Institute reserves the right to monitor grantee activity in this area to ascertain if patents on large numbers of atlases and bioinformatics tools are being filed. Where appropriate, grantees may work with the private sector to make unique resources available to the wider biomedical research community at a reasonable cost. Applicants may request funds to defray the costs of sharing resources, with adequate justification. 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 Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. 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 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/guide/notice-files/not98-024.html. LETTER OF INTENT Prospective applicants are asked to submit, by April 19, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the PA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows program staff to estimate the potential review workload and avoid conflict of interest in the review. The letter of intent is to be sent to: Michael F. Huerta, Ph.D. Division of Basic and Clinical Neuroscience Research National Institute of Mental Health 6001 Executive Boulevard, Room 7196 MSC 9645 Bethesda, MD 20892-9645 Telephone: (301) 443-3563 Fax: (301) 443-1731 Email: mhuerta@helix.nih.gov APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 4/98) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research or from the Office of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone (301) 435-0714, fax (301) 480- 0525, Email: GrantsInfo@NIH.GOV. It is also available at http://www.nih.gov/grants/forms.htm. In addition, the PA title and number must be typed in section 2 of the face page of the application form and the YES box must be marked. 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 courier/express service) At the time of submission, two additional copies of the application must be sent to: Michael F. Huerta, Ph.D. Division of Basic and Clinical Neuroscience Research National Institute of Mental Health 6001 Executive Boulevard, Room 7196 MSC 9645 Bethesda, MD 20892-9645 Telephone: (301) 443-3563 Fax: (301) 443-1731 Email: mhuerta@helix.nih.gov Each year, applications must be received by May 19. If an application is received after that date, it will be returned to the applicant without review. This date pertains to new applications, amended and resubmitted applications, and competitive renewal applications. The Center for Scientific Review (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 substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Applications will be assigned on the basis of established PHS referral guidelines. For administrative purposes, applications will be assigned initially to NIMH. Applications will be evaluated for scientific and technical merit by an appropriate scientific review group convened by NIMH in accordance with the review criteria stated below. 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, assigned a priority score, and receive a second level review by the appropriate national advisory council or board. Review Criteria The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments reviewers will be asked to discuss the following aspects of 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 proposed research address an important problem? If the aims of the application are achieved, how will scientific capabilities be advanced? What will be the effect of these advances on the ability to make sense and use of nervous system gene expression data? (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? Is the approach iterative, allowing for early informatics solutions to be used while latter versions are elaborated upon? Is the proposed approach adequate to allow for interoperability with other efforts? Will this effort be generalizable, extensible and scalable? Will the validity and reliability of tools be assessed appropriately? If multiple sites are involved, is there adequate coordination and oversite among the various groups? Are the plans for sharing resources generated adequate? (3) Innovation: Does the project employ novel concepts, approaches, or methods? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? Will the project result in new or enhanced capabilities? (4) Investigator: Is the investigator or are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)? Is there sufficient expertise in the areas of informatics, molecular biology and neuroscience? (5) Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Does the proposed research and development take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? 6) Budget and duration: Are the proposed budget and duration appropriate in relation to the proposed research and development? 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. AWARD CRITERIA Applications will compete for available funds with all other approved applications. The following will be considered in making funding decisions: o Quality of the proposed project as determined by peer review o availability of funds o program priority INQUIRIES Inquiries concerning this PA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Michael F. Huerta, Ph.D. Division of Basic and Clinical Neuroscience Research National Institute of Mental Health 6001 Executive Boulevard, Room 7196 MSC 9645 Bethesda, MD 20892-9645 Telephone (301) 443-3563 FAX: (301) 443-1731 Email: mhuerta@helix.nih.gov Cheryl A. Kitt, Ph.D. Division of Convulsive, Infectious and Immune Disorders National Institute of Neurological Disorders and Stroke 6001 Executive Boulevard, Room 2116 MSC 9160 Bethesda, MD 20892-9160 Telephone: (301) 496-1431 Fax: (301) 402-2060 Email: ck82j@nih.gov Bradley C. Wise, Ph.D. Neuroscience and Neuropsychology of Aging Program National Institute on Aging 7201 Wisconsin Avenue, Suite 3C307, MSC 9205 Bethesda, MD 20892-9205 Telephone: (301) 496-9350 Fax: (301) 496-1494 Email: bw86y@nih.gov Yuan Liu, Ph.D. Division of Basic Research National Institute on Alcohol Abuse and Alcoholism 6000 Executive Boulevard, Suite 402, MSC 7003 Bethesda, MD 20892-7003 Telephone: (301) 594-6382 Fax: (301) 594-0673 Email: yliu@willco.niaaa.nih.gov Nancy Pilotte, Ph.D. National Institute on Drug Abuse Division of Basic Research 6001 Executive Boulevard, Room 4284 MSC 9555 Bethesda, MD 20892-9555 Telephone: (301) 443-6975 Fax: (301) 594-6043 Email: np22f@nih.gov Maria Y. Giovanni, Ph.D. National Eye Institute 6120 Executive Boulevard, Suite 350, MSC 7164 Bethesda, MD 20892-7164 Telephone: (301) 496-0484 Fax: (301) 402-0528 Email: myg@nei.nih.gov Deborah Henken, Ph.D. Center for Research for Mothers and Children National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 4B01, MSC 7510 Bethesda, MD 20892-7510 Telephone: (301) 496-5541 Fax: (301) 480-0303 Email: dh50g@nih.gov Rochelle Small, Ph.D. Division of Human Communication National Institute on Deafness and Other Communication Disorders 6120 Executive Blvd. MSC 7180, Room 400C Bethesda, MD 20892-7180 Telephone: (301) 402-3464 FAX: (301) 402-6251 Email: rochelle_small@nih.gov Direct inquiries regarding fiscal matters to: Diana S. Trunnell Grants Management Branch National Institute of Mental Health 6001 Executive Boulevard, Room 6115 MSC 9605 Bethesda, MD 20892-9605 Telephone: (301) 443-2805 Fax: (301) 443-6885 Email: Diana_Trunnell@nih.gov Karen D. Shields Grants Management Branch National Institute of Neurological Disorders and Stroke 6001 Executive Boulevard, Room 3261 MSC 9190 Bethesda, MD 20892-9190 Telephone: (301) 496-9231 Fax: (301) 402-0219 Email: shieldsk@ninds.nih.gov Joseph Ellis Grants Management Officer National Institute on Aging 7201 Wisconsin Avenue, Suite 2N212, MSC 9205 Bethesda, MD 20892-9205 Telephone: (301) 496-1472 Fax: (301) 402-3672 Email: ellisj@exmur.nia.nih.gov Linda Hilley Office of Planning and Resource Management National Institute on Alcohol Abuse and Alcoholism 6000 Executive Boulevard, Suite 504, MSC 7003 Bethesda, MD 20892-7003 Telephone: (301) 443-4703 Fax: (301) 443-3891 E-mail: lhilley@willco.niaaa.nih.gov Kathleen Moy Grants Management Specialist National Eye Institute Executive Plaza South 6120 Executive Blvd., Suite 350, MSC 7164 Bethesda, MD 20892-7164 Telephone: (301) 496-5884 Fax: (301) 496-9997 Email: klm@nei.nih.gov E. Douglas Shawver Grants Management Branch National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8A17, MSC 7510 Bethesda, MD 20892-7510 Telephone: (301) 496-1303 Fax: (301) 402-0915 Email: Shawverd@exchange.nichd.nih.gov Gary Fleming Grants Management National Institute on Drug Abuse 6001 Executive Boulevard, Room 3131, MSC 9541 Rockville, MD 20892-9542 Telephone: (301) 443-6710 FAX: (301) 594-6847 Email: gf6s@nih.gov Sharon Hunt Division of Extramural Activities National Institute on Deafness and Other Communication Disorders 6120 Executive Boulevard, Room 400B, MSC 7180, Bethesda, MD 20892-7170 Telephone: (301) 402-0909 FAX: (301) 402-1757 Email: sh79f@nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.242 (NIMH), 93.279 (NIDA), 93.273 (NIAAA), 93.866 (NIA), 93.853 (NINDS), 93.173 (NIDCD), 93.865 (NICHD), and 93.867 (NEI). 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 or Health Systems Agency review. Awards 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 non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.


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