RFA-NS-02-001: MICROARRAY CENTERS FOR RESEARCH ON THE NERVOUS SYSTEM

Department of Health
and Human Services (HHS)

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MICROARRAY CENTERS FOR RESEARCH ON THE NERVOUS SYSTEM Release Date: February 13, 2001 RFA: RFA-NS-02-001 National Institute of Neurological Disorders and Stroke National Institute of Mental Health Letter of Intent Receipt Date: May 15, 2001 Application Receipt Date: July 13, 2001 PURPOSE The National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Mental Health (NIMH) invite applications for support of Microarray Centers. These Centers will support gene expression profiling in the nervous system through the application of microarray technologies. The Microarray Centers, which will function as a consortium, will provide reagents, services, and training to the neuroscience community, on a fee-for-service basis. The term consortium is used here to refer to the Centers that are funded through this RFA, and not to refer to non-grantee, participating organizations. RESEARCH OBJECTIVES Background: Oligonucleotide and cDNA microarrays are used to make quantitative or relative measurements of gene expression. The microarrays contain nucleotide sequences corresponding to known genes or expressed sequence tags. A single array can contain thousands of genes, which may represent a significant subset of the genes, or even the entire genome, of an organism. A comparison of cells or tissues from experimental and control preparations provides data on differences in expression levels between the two conditions. Changes in gene expression of ubiquitously expressed genes might reveal clues to underlying, widespread alterations of cellular physiology. Changes in expression patterns of genes that are regulated temporally or spatially within the organism might provide information on developmental or disease processes. Changes in one or a few genes might lead to the discovery of individual molecular targets for drug therapy. Drawbacks to the application of microarray technologies to research problems include the expense of performing the experiments, and, in some cases, significant technical barriers to success. It is the goal of this RFA to establish up to three Microarray Centers that will work together in a consortium arrangement to provide microarray reagents, services, and training to the neuroscience community. Objective and Scope: NINDS and NIMH will use the U24 Resource-Related Research Projects Cooperative Agreements funding mechanism to establish up to three Microarray Centers. The Centers will serve as regional and national resources to the neuroscience community. Each Center will be directed by a Principal Investigator (PI), and will receive guidance from NINDS and NIMH program staff to assist with identification and implementation of appropriate strategies and priorities. Although the Centers may specialize with regard to equipment, expertise, and proprietary reagents, they will work closely together in a consortium arrangement. The efforts of the Centers will be coordinated, strategically and functionally, with the result that the Centers will function as a single, national resource. Coordination of the Centers will be accomplished through close collaboration between the Center PIs, leadership and direction from NINDS and NIMH program staff, and oversight by a Steering Committee. A Consortium Advisory Panel (CAP), composed of experts not affiliated with the Centers, will be formed. The CAP will advise Center PIs and NINDS and NIMH program staff on the organization and operation of the microarray consortium. The CAP will address long-term strategic issues and policies, and will also assist with the development of general guidelines for daily operations, including the acceptance/rejection of projects and prioritization of workload. The Microarray Centers will provide services to NINDS-funded and NIMH-funded investigators to support microarray analyses on the nervous system. These services will include a broad spectrum of activities. The Centers will produce arrays for use by the neuroscience community. These arrays may be standard, nervous system-specific arrays designed by the Centers for general use, or they may be custom arrays suited to the needs of smaller groups of investigators. The Centers will run array experiments, including hybridization reactions, array reading, and data analyses. The Centers will also advise and train the neuroscience community. They may assist with experimental design, and advise on how best to obtain experimental results. The Centers will train neuroscientists on the effective use of microarray experimental techniques, in an effort to disseminate expertise throughout the neuroscience community. The services provided by the Centers will be on a fee-for-service basis. Fees charged will recover product costs and service delivery costs. Research and development costs for array production and development of best practices will not be recovered, except in specific cases where custom arrays are developed for limited uses. A significant portion of the first-year funding may be requested for equipment. Applications in response to this RFA should include detailed plans for the advisory, training, research and development, and fee-for-service functions of the Centers. Research projects associated with the Centers, including those of the PIs, are expected to have independent funding. SPECIAL REQUIREMENTS Program Income: Fees charged by the Centers will constitute Program Income. Program Income is gross income earned by the awardee that is directly generated by a supported activity or earned as a result of the award (see 45 CFR 74.2 and 74.24 for additional information). An estimate of the amount and source of Program Income that will be generated as a result of the award must be included on the Checklist Page of all competing and non-competing continuation applications. Net program income earned during a budget period must be reported on the annual Financial Status Report (FSR) (except for Program Income earned as a result of inventions, to which special rules apply). Costs incident to the generation of Program Income may be deducted from gross income to determine Program Income to be reported on the FSR, provided that these costs have not been charged to the award. Program Income earned during the project period shall be retained by the award recipient and used in the following way: The first $25,000 earned during a budget period is added to funds committed to the project or program, and used to further eligible project or program objectives, Any amount over $25,000 earned during a budget period is to be deducted from the total project or program allowable costs in determining the net allowable costs on which the federal share of costs is based. The NINDS and NIMH may offset a future award by this amount or reauthorize it for expenditure on a future award. Pre-application Meeting: The NINDS and NIMH strongly encourage all potential applicants to attend a pre- application meeting at the National Institutes of Health (NIH) in June 2001. This meeting will provide NINDS and NIMH program staff with the opportunity to clarify any requirements of the RFA and, thereby, enable applicants to present the strongest possible case for support. After the date, time, and place of the pre-application meeting have been set, the details will be announced in the NIH Guide for Grants and Contracts. For potential applicants who are unable to attend, a summary will be made available within two weeks of the meeting. Biannual Meetings: Center PIs and scientists, along with NINDS and NIMH program staff, will make up a Steering Committee that will meet twice annually at the NIH. Applications in response to this RFA should include a request for funds to cover the expense of attending the biannual Steering Committee meetings in Bethesda, Maryland. Data Sharing: Genomic data from microarray analyses are useful for many purposes. It is very important that the data generated from experiments supported by the Centers are shared with the broader scientific community. The consortium of Centers will require data sharing by users of the Centers products and services. The Centers will collect these data and share them. The Centers are encouraged to share data on the National Center for Biotechnology Information Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/), and to submit data to other public gene expression databases specified by the Steering Committee. Applications in response to this RFA should include a detailed plan for data sharing, which will be considered during review of the proposals. Terms and Conditions of Award: These special Terms of award are in addition to and not in lieu of otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR Parts 74 and 92, and other HHS, PHS, and NIH Grant Administration policy statements. The administrative and funding instrument used for this program is a cooperative agreement (U24). As described previously, the dominant role and prime responsibility for the activity resides with the awardee(s) for the project as a whole, although specific tasks and activities in carrying out the project will be shared among the awardees, NINDS and NIMH program staff, and the CAP. 1. Awardee Rights and Responsibilities Awardees, as Center PIs, have primary responsibilities to define objectives and approaches, and to plan and conduct the activities of the Centers that they manage. Awardees will collaborate with other Center PIs, and coordinate Center developmental and fee-for-service activities with those of the other Centers. Each Center PI must agree to participate with NINDS and NIMH program staff and the CAP in coordinating the activities of the Centers, with the result that the Centers will function as a single consortium. Although each Center will be independently funded and managed, the planning and implementation of Center activities will be done in a way to maximize the overall effectiveness of the consortium of Centers. Each Center will maintain a log of Center usage by NINDS and NIMH grantees that records the products and services provided to the grantees, the fees charged for the products and services, and the institute (NINDS or NIMH) from which the grantee receives support. Prior to each non-competing renewal of these awards, each Center will submit to the NIH a progress report that describes the activities and accomplishments of the Center for the preceding award period, and the goals to be accomplished during the renewal period. The progress report will include the log of Center usage. The contents of the progress report will be used by NINDS and NIMH program staff, along with other information, to determine the amount of funding the Center will receive for the renewal period. Center PIs will attend, and participate in, biannual Steering Committee meetings at the NIH. Awardees will be voting members of the Steering Committee, and will accept any modification, deletion, or addition of Center activities that is approved by the Steering Committee. 2. NINDS and NIMH Program Staff Responsibilities NINDS and NIMH program staff, as Project Scientists, will have substantial scientific-programmatic involvement during conduct of this activity, through technical assistance, advice, and coordination above and beyond normal program stewardship for grants. The NIH Project Scientists will have a single, combined vote on the Steering Committee, and will participate with the other members of the committee in planning the overall structure and strategy of the consortium of Centers. Microarray technologies are evolving rapidly, and program staff will play an active role in assuring that Centers remain on the cutting edge of the research technologies. This role will be carried out by assisting the Center PIs and the CAP with assessing the current state of the technologies and methodologies for gene expression profiling. The Project Scientists will select and recruit the members of the CAP, who will each serve a three-year term. The Project Scientists will also have the responsibility of replacing CAP members that choose to leave the CAP. Project Scientists may, but are not required to, consult with Center PIs, CAP members, or other outside advisors when recruiting members of the CAP. NINDS and NIMH program staff will determine the amount of support that will be awarded to each Center as a non-competing renewal. The progress report received from each Center, along with other information, will be used to make this determination. The criteria used for this decision will include, but not be limited to, Center production, customer satisfaction, and successful performance of the Center as a member of the consortium. NINDS and NIMH program staff will assist with and facilitate the coordination and research efforts of the Centers, but will not direct these activities. 3. Collaborative Responsibilities Consortium Advisory Panel The CAP will be composed of between four and six experts not associated with the Centers. This panel will provide oversight to the consortium, and advice to the Steering Committee and NIH. CAP members will provide technical and operational advice concerning both long-term developments and day-to-day operations at the Centers. The CAP members will choose a chairperson, who will coordinate communication among the members, and between the CAP, the Centers, and the Project Scientists. The CAP members will not vote on the Steering Committee, but may be invited to attend Steering Committee meetings, if attendance would significantly facilitate Steering Committee business. Periodically, at intervals determined by the Steering Committee, a formal request for advice on specific subjects will be submitted to the CAP. The CAP will convene to consider and formulate opinions on the questions submitted to it. NINDS and NIMH program staff will consider the opinions of the CAP with regard to overall consortium functioning, and the performance of individual Centers, when making determinations for renewal funding. Steering Committee A Steering Committee composed of the Center PIs, one additional manager or scientist from each Center, two NINDS Project Scientists, and one NIMH Project Scientist, will convene at the NIH twice annually. Each year the Steering Committee will select a chairperson who will serve a one-year term. The chairperson of the Steering Committee may not be a NINDS or NIMH Project Scientist. Each Center will have one Steering Committee vote, and the NIH will have one Steering Committee vote. In cases where members do not agree, any member may ask the chairperson to solicit a vote. In order for a decision or course of action to be finalized by the Steering Committee, a majority of the possible votes must be cast in favor of the decision or course of action. The Steering Committee will be the main governing board of the consortium of Microarray Centers. The committee may take actions, deemed appropriate by vote of the members when necessary, to facilitate the functioning of the consortium. Such actions might include, but are not limited to, formation of sub-committees, consultations with outside persons, and specialization of the Centers. Awardees will be required to accept and implement the common protocol and procedures approved by the Steering Committee. 4. Arbitration Any disagreement that may arise on scientific/programmatic matters (within the scope of the award), between award recipients and the NINDS or the NIMH may be brought to arbitration. An arbitration panel will be composed of three members one chosen by the Steering Committee (with NIH not voting) or by the individual awardee in the event of an individual disagreement, a second member selected by the NINDS and NIMH, and the third member selected by the two prior selected members. This special arbitration procedure in no way affects the awardee’s right to appeal an adverse action that is otherwise appealable in accordance with the PHS regulations at 42 CFR Part 50, Subpart D and HHS regulation at 45 CFR Part 16. MECHANISM OF SUPPORT The administrative and funding instrument to be used for this program will be the NIH Resource-Related Research Projects Cooperative Agreements award mechanism (U24), an assistance mechanism in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during performance of the activity. Under the cooperative agreement, the NIH purpose is to support and/or stimulate the recipient’s activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. The total project period for an application submitted in response to this RFA may not exceed three (3) years. At this time, NINDS and NIMH have not determined whether or how this solicitation will be continued beyond the present RFA. The earliest anticipated award date is April 1, 2002. FUNDS AVAILABLE NINDS and NIMH intend to commit up to $3.5 million in total costs to fund up to three successful applications in FY 2002 in response to this RFA. Applicants may request up to three years of support. Although the financial plans of NINDS and NIMH provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic, 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. INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding scientific and other application-related issues, and inquiries specific to NINDS to: Thomas Miller, Ph.D. Technology Development National Institute of Neurological Disorders and Stroke 6001 Executive Blvd., Room 2139 Bethesda, MD 20892 Tel: 301-496-1779 Fax: 301-402-1501 Email: tm208y@nih.gov Direct inquiries specific to NIMH to: Hemin R. Chin, Ph.D. Genetics Research Branch Division of Neuroscience & Basic Behavioral Science National Institute of Mental Health 6001 Executive Blvd., Room 7190 Bethesda, MD 20892 Tel: 301-443-1706 Fax: 301-443-9890 Email: hc7v@nih.gov Direct inquiries regarding review issues to: Lillian Pubols, Ph.D. Chief, Scientific Review Branch National Institute of Neurological Disorders and Stroke 6001 Executive Blvd., Room 3208 Bethesda, MD 20892 Tel: 301-496-9223 Fax: 301-402-0182 Email: lp28e@nih.gov Direct inquiries regarding fiscal matters to: King P. Bond, Jr. Grants Management Branch National Institute of Neurological Disorders and Stroke 6001 Executive Blvd., Room 3258 Bethesda, MD 20892 Tel: 301-496-9231 Fax: 301-402-0219 Email: kb33s@nih.gov LETTER OF INTENT Prospective applicants are asked to submit, by May 15, 2001, a Letter of Intent that includes a descriptive title, the name, address, telephone number, and email address of the PI, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a Letter of Intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows institute staff to estimate the potential review workload and avoid conflict of interest in the review. The Letter of Intent is to be sent to: Thomas Miller, Ph.D. Technology Development National Institute of Neurological Disorders and Stroke 6001 Executive Blvd., Room 2139 Bethesda, MD 20892 Tel: 301-496-1779 Fax: 301-402-1501 Email: tm208y@nih.gov SCHEDULE SUMMARY Letter of Intent Receipt Date: May 15, 2001 Application Receipt Date: July 13, 2001 Peer Review Date: November 2001 Council Review: February 2002 Early Anticipated Start Date: April 1, 2002 APPLICATION PROCEDURES The Research grant application form PHS 398 (rev. 4/98) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research, and from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, Room MSC 7910, Bethesda, MD 20892, telephone 301-710-0267, email: GrantsInfo@nih.gov. The RFA label available in the PHS 398 (rev. 4/98) application form must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. There is a sample RFA label available at: http://grants.nih.gov/grants/funding/phs398/label-bk.pdf. Note that this is in pdf format. Submit a signed, typewritten original of the application, including the Checklist, and three (3) signed photocopies, in one package to: CENTER FOR SCIENTIFIC REVIEW NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application must be sent to: Lillian Pubols, Ph.D. Chief, Scientific Review Branch National Institute of Neurological Disorders and Stroke 6001 Executive Blvd., Room 3208 Bethesda, MD 20892 Rockville, MD 20852 (for express/courier service) Applications must be received by the application receipt date listed in the heading of this RFA. If an application is received after that date, it will be returned to the applicant without review. The Center for Scientific Review (CSR) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by CSR and responsiveness by NINDS. Incomplete applications will be returned to the applicant without further consideration. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NINDS 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 the applications under review, will be discussed, assigned a priority score, and receive a second level review by the NINDS and NIMH National Advisory Councils. 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? (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? In addition to the above criteria all applications will also be reviewed with respect to the following: o The adequacy of plans to include both genders, minorities and their subgroups, and children as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. o The reasonableness of the proposed budget and duration in relation to the proposed research. o The adequacy of the proposed protection for humans, animals, or the environment, to the extent they may be adversely affected by the project proposed in the application. o The adequacy of the proposed plan to provide advice and training to the neuroscience community. o The adequacy of the proposed fee-for-service plan, including administration and funds management o The adequacy of the proposed plan to share data. AWARD CRITERIA Award criteria that will be used to make award decisions include: o scientific merit (as determined by peer review) o availability of funds o programmatic priorities, and program balance o geographic balance 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 UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research," published in the NIH Guide for Grants and Contracts on August 2, 2000 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html), a complete copy of the updated Guidelines are available at http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm. The revisions relate to NIH defined Phase III clinical trials and require: a) all applications or proposals and/or protocols to provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable, and b) all investigators to report accrual, and to conduct and report analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. NIH POLICY AND GUIDELINES ON THE 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://grants.nih.gov/grants/guide/notice-files/not98-024.html Investigators also may obtain copies of these policies from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. URLS IN NIH GRANT APPLICATIONS OR APPENDICES All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Reviewers are cautioned that their anonymity may be compromised when they directly access an Internet site. HEALTHY PEOPLE 2010 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This RFA, "Microarray Centers for Research on the Nervous System" is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople. AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.853 (NINDS), and 93.242 (NIMH). Awards are made under authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and administered under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant 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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