RFA-HG-01-002: BAC LIBRARY PRODUCTION

Department of Health
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BAC LIBRARY PRODUCTION Release Date: April 18, 2001 RFA: RFA-HG-01-002 (Request for competing renewal applications, see NOT-HG-05-003) National Human Genome Research Institute (http://www.nhgri.nih.gov) National Center for Research Resources (http://www.ncrr.nih.gov) Letter of Intent Receipt Date: June 1, 2001 Application Receipt Date: June 27, 2001 PURPOSE The National Human Genome Research Institute (NHGRI) and the National Center for Research Resources (NCRR) invite applications for support of efforts to produce BAC libraries from the DNA of a number of different eukaryotic organisms that are important in biomedical and biological research. Under this initiative, NHGRI and NCRR expect to support the production of 10 new libraries in the first 12-18 months of funding, and to develop the capacity to double this rate subsequently if there is a continuing demand for new BAC libraries, with the possibility of constructing as many as 50 BAC libraries in three years. 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 Request for Applications (RFA), Title of RFA, is related to several priority areas including cancer, heart disease and stroke, diabetes and chronic disability conditions, and maternal and infant health. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople/. ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and non- profit organizations, public and private, such as universities, colleges, private companies, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from foreign institutions will be accepted. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORT The administrative and funding mechanism to be used to support this program will be the Cooperative Agreement (U01), an "assistance" mechanism, which is distinguished from a regular research grant in that substantial scientific and/or programmatic involvement by NHGRI and NCRR staff with the awardee is anticipated. The cooperative agreement is used when participation by NIH staff is warranted to support and/or stimulate the recipient"s activity by involvement in and otherwise working jointly with the award recipient in a partner role, NIH staff will not assume direction, prime responsibility, or a dominant role in the activity. Details of the responsibilities, relationships, and governance of the studies funded under cooperative agreement(s) are discussed later in this document under the section "Terms and Conditions of Award". This RFA is a one-time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to the customary peer review procedures. The anticipated award date is December 1, 2001. FUNDS AVAILABLE The NHGRI and NCRR together intend to commit a total of approximately $2.5 million in FY 2002 to fund two to four new and/or competitive continuation grants in response to this RFA. Applicants may request a project period of up to three years. Because the nature and scope of the research proposed by different investigators may vary, it is anticipated that the size of each award would also vary. Although the financial plans of the NHGRI and NCRR 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. RESEARCH OBJECTIVES Background Over the past several years, the bacterial artificial chromosome (BAC) has emerged as the vector system of choice for the construction of the large- insert chromosomal DNA libraries that are needed in genomic studies. The BAC cloning system allows the isolation of genomic DNA fragments that are large enough (80 to >200 kilobases [kb]) to be useful for both genomic sequence determination and for a variety of functional studies. BAC clones are less prone to artifacts than either of the other available vector systems for large-fragment cloning, cosmids (cosmid libraries generally contain considerably more unstable clones than BAC libraries) and yeast artificial chromosomes (YACs, BAC libraries contain significantly fewer chimeric clones). To date, the complete sequencing of all large eukaryotic genomes (including C. elegans, D. melanogaster, A. thaliana and H. sapiens) has involved BAC clones. Recent experience in sequencing the human genome shows that determination of the sequence of a large, repeat-rich genome requires the availability of a clone map for localizing sequence contigs and for assembling regions containing repeated sequences. While whole genome shotgun sequence data will likely be part of any strategy adopted to sequence such genomes, it does not obviate the need for well-mapped BAC clones and therefore for BAC libraries. Because BAC clones are relatively large and appear to represent an organism"s genome well, the BAC system will also be the vehicle of choice for the isolation of targeted regions of genomic DNA from additional human individuals, other mouse strains, or other organisms for specific biological studies. BAC libraries representing the genomes of a small number of organisms have been constructed and are publicly available http://www.chori.org/bacpac/home.htm. It is of concern to the NHGRI and NCRR that the current national capacity for making BAC libraries may be too low to meet future demand, and that BAC library construction could become a bottleneck in the advancement of the application of genomic approaches to biomedical and biological research. Research Objectives NHGRI currently funds only a limited amount of BAC library construction, sufficient to produce about two 10-fold deep mammalian libraries per year. With the increasing interest in genomic approaches to biological research, there is concern that this level will not be sufficient to produce the number of libraries that will be needed and that the consequent lack of availability of more libraries could become a bottleneck to research. To increase the number of available BAC libraries, NHGRI and NCRR wish to encourage the establishment of additional BAC library-making capacity. The primary purpose of this solicitation is to ensure an adequate capacity for BAC library making and to generate a large number of BAC libraries that will be generally useful to the biological and biomedical research communities. There are several factors that affect the difficulty of and time required to make a BAC library, and therefore that affect the cost of a library. Prominent among these are the size of the genome being cloned, the method used to generate the sub-genomic fragments being cloned, the number of clones in the library, and the average size of the cloned genomic DNA fragments (inserts). Typically, the most useful BAC libraries contain at least a 10-fold (10X) representation of the organism"s genome (an average region of the genome is present ten times in the library, the product of the number of clones and the average insert size divided by the size of the genome determines the "depth," or "fold coverage" of the library). However, the cloning efficiency is not usually uniform for all of the fragments. Therefore, to ensure that a library contains as much of the genome as possible, libraries with as much as 20X representation have been produced. Similarly, typical BAC libraries contain inserts that average about 150 kb in size. However, for some purposes, such as generating a fingerprint map of the genome, larger inserts are preferable. Libraries containing fragments of 200 kb average size have been made, but are usually considerably more difficult and more expensive to construct than those containing smaller inserts. There are basically two methods used to generate DNA fragments for library construction. The most commonly used method is partial digestion of genomic DNA with a restriction enzyme. This is a proven technique that is relatively easy to control. However, the sites at which the DNA is cut are fixed by the location of the restriction enzyme recognition sites, so the inserts in these libraries are not random. Furthermore, if the restriction sites are located in repeated DNA sequences, there will be problems in making use of the end sequence data. Random DNA fragments can be generated by shearing the DNA. However, the techniques for producing and cloning sheared DNA fragments in the 100 to 200 kb range are not routine, and the methods for construction of randomly-sheared BAC libraries are still under development. Applicants should take into account the need to improve the process of library production, as well as the need for a reliable level of BAC library construction capacity. As a guideline, the NHGRI and NCRR are planning to support a national capacity to make at least ten 10X libraries of human-sized genomes (three gigabases) per year. Applicants may propose any level of capacity that they feel is appropriate to their capabilities, NHGRI and NCRR are willing to fund as many as four different laboratories under this RFA. Applicants should also address the issues of library quality and cost of library production. The quality of a BAC library is extremely important in determining the actual utility of the library. Applicants must propose a plan for assessing the quality of the libraries produced including, but not limited to, parameters such as the fraction of clones containing inserts, the distribution of insert sizes, the fraction of chimeric clones, and the fraction of unstable clones. At present, the relatively high cost of making a BAC library limits the number of libraries that can be constructed each year with NHGRI and NCRR support. To the degree that library production costs can be reduced, the number of libraries produced each year could be increased without an increase in overall spending on this component of the NHGRI and NCRR research programs. Applicants should, therefore, discuss plans for improving methods for BAC library construction, particularly those that would lead to a reduction in the cost of library production over the term of the award (three years). In addition to approaches based on increasing the efficiency of current library production methods, applicants may include a technology development component in their proposals. Applicants need not attempt to enumerate all of the organisms for which they plan to prepare BAC libraries. At present, neither the NIH nor the applicants can predict the actual needs that the research enterprise will have for particular BAC libraries over the next few years. The NHGRI is currently developing a process that will allow the establishment and dissemination, on an on-going basis, of a set of priorities for NHGRI-supported genomic research, including the on-going need for new BAC libraries. By the time applications submitted in response to this RFA are funded, the NHGRI will have implemented that process and, through the cooperative agreement mechanism, NHGRI staff and awardees will be able to decide which BAC libraries to produce and on what schedule to produce them. Other institutes and centers at the NIH may also identify, or may have already identified, specific organisms for which they will want BAC libraries constructed. For example, the NCRR has a particular interest in BAC libraries from non-human primate species. These priorities will be integrated into those identified by the NHGRI for BAC library making at the time of award. Applicants should describe their plans for the release and dissemination of data about the libraries they produce. While funds for distribution of the libraries should not be requested in applications responding to this RFA, applicants should discuss any plans they have ,for library distribution (for example, distribution by a company to which the library is given or through a distribution service set up by the awardee which recovers its cost through charges to the requestors). The adequacy of the plans for dissemination of the libraries and data about the libraries is included as a review criterion for this RFA. Once a dissemination plan is worked out that is satisfactory to the grantee, NHGRI and NCRR it will be made a condition of the award. Applicants should also be familiar with the NIH statements regarding intellectual property of resources developed with Federal funds (http://www.ott.nih.gov/policy/rt_guide_final.html) In summary, applicants for awards under this RFA: o should provide information about their prior experience in making BAC libraries, o should discuss all issues currently associated with the construction, evaluation and distribution of BAC libraries, o should address the approaches they propose to take toward library construction, o should address the issue of library production costs and ways to reduce costs, o should discuss approaches to disseminating of the libraries and information about the libraries, o may include proposals to improve library-making technology, and o do not have to propose a set of specific organisms for which libraries will be made. SPECIAL REQUIREMENTS FOR COOPERATIVE AGREEMENTS Definitions ARBITRATION PANEL: A panel that is formed to review scientific or programmatic disagreement (within the scope of the award) that may arise between an award recipient and NHGRI. It will be composed of three members: (1) a designee of the awardee, (2) an NHGRI designee, and (3) a third designee with relevant expertise who is chosen by the other two. The Arbitration Panel will help resolve both scientific and programmatic issues that develop during the course of work and that restrict progress. AWARDEE: The institution to which the cooperative agreement is awarded. COOPERATIVE AGREEMENT: An assistance mechanism in which there is anticipated to be substantial involvement by NHGRI program staff with the recipient organization during the performance of the planned activity. NHGRI PROGRAM DIRECTOR: A scientist of the NHGRI extramural staff who provide normal stewardship for the awards and who, in addition, has substantial scientific/programming involvement during conduct of this activity, as defined in the terms and conditions of award. The nature of this involvement is described below. PRINCIPAL INVESTIGATOR (P.I.): The person who assembles the project, is responsible for submitting the application in response to this RFA, and is responsible for the performance of the project. The Principal Investigator will coordinate project activities scientifically and administratively. SCIENTIFIC ADVISORY PANEL (SAP): A panel that evaluates the progress of the NHGRI large-scale sequencing program and provides recommendations to the Director, NHGRI, about continued support of all components of the program. The Advisory Panel is composed of four to six senior scientists with relevant expertise who are not P.I.s of a cooperative agreement involved in large-scale genomic sequencing or BAC library production. Terms and Conditions of Award The following terms and conditions will be incorporated into the award statement of each cooperative agreement awarded under RFA HG-01-002 and will be provided to the Principal Investigator, as well as the appropriate institutional official, at the time of award. The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, DHHS grant administration regulations at 45 CFR Parts 74 and 92 [Part 92 are applicable when State and local Governments are eligible to apply], as are other DHHS, NIH, and NIH grant administration policies: (1) The administrative and funding instrument used for this program will be the Cooperative Agreement (U01). The cooperative agreement is an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during the 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. Consistent with this concept, the dominant role and prime responsibility for the BAC library production project as a whole will reside with the awardee(s), although specific tasks and activities in carrying out the study will be shared among the awardee(s) and the NHGRI Program Director. (2) P.I. Rights and Responsibilities: The P.I. will have the primary responsibility for defining the details for the BAC library production project within the guidelines of RFA HG-01-002 and for performing the scientific activities. The P.I. will agree to accept close coordination, cooperation, and participation of NHGRI staff in those aspects of scientific and technical management of the project as described under "NHGRI Program Staff Responsibilities." The P.I. of a BAC library production center will: o Determine experimental approaches, design protocols, set project milestones and conduct experiments, o Ensure that the BAC libraries produced meet the quality standards and cost agreed upon at the time of award, o Ensure that the BAC clone resources developed as part of this project are made publicly available and that results are published, o Ensure that the decisions about the BAC libraries produced under NHGRI and NCRR funding meet the needs of the Institute/Center"s programs, as determined at the time of initiation of each library-making effort, o Coordinate and collaborate with other U.S. and international groups producing BAC libraries, o Be required to accept and implement any common guidelines and procedures developed for the BAC library production program. (3) NHGRI Program Staff Responsibilities: The NHGRI Program Director will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination. However, the role of NHGRI staff will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus between the Principal Investigator(s) and NHGRI staff. The Program Director will: o Participate in discussing research priorities, including choice of organisms from which to make BAC libraries, deciding optimal research approaches and protocol designs (including quality assessment), and contributing to any necessary adjustment of research protocols or approaches. o Serve as liaison, helping to coordinate activities among and for the awardees, including acting as a liaison to the NHGRI and the other Institutes and Centers of the NIH, and as an information resource about extramural genome research activities. o Coordinate the efforts of the BAC library makers with the NHGRI sequence production program, with other U.S. large-scale sequencing efforts and with the international sequencing community. o Assist awardees in the development, if needed, of policies for dealing with situations that require coordinated action. o Periodically report on the progress of the BAC library construction program to the NHGRI Director, the Sequencing Advisory Panel and other interested NIH Institutes and Centers. o Assist in promoting the availability of the BAC libraries and related resources developed in the course of this project to the scientific community at large. o Retain the option to recommend, with the advice of the Scientific Advisory Panel, the withholding or reduction of support from any cooperative agreement that substantially fails to achieve its goals at the quality and cost agreed to at the time of award, fails to remain state of the art in its library- making capabilities, or fails to comply with the Terms and Conditions of the award. (4) Collaborative Responsibilities The awardees and Program Director will be responsible for: o Discussing progress in meeting the research community’s need for BAC libraries. o Advising NHGRI as to how the requisite number of BAC libraries can be met within the stated goals of time and accuracy, and within budget. o Helping to develop uniform procedures for library quality assessment. o Awardees and Program Directors will be required to accept and implement the common guidelines and procedures mutually agreed upon. (5) Scientific Advisory Panel (SAP) The Scientific Advisory Panel will be responsible for reviewing and evaluating the progress of the BAC library-making activity, and its coordination with large-scale genomic sequencing and other uses of BAC clones in genomic research. The membership of the SAP is described in the Definitions section, above. The membership of the SAP may be enlarged permanently, or on an ad hoc basis, as needed. At least once a year, there will be an opportunity, either in a meeting or by conference call, for the SAP members to interact directly with the P.I.s of the BAC library-making awards. Annually, the SAP will make recommendations regarding progress of the BAC library-making effort and present advice about changes, if any, which may be necessary in the BAC library program to the Director, NHGRI. (6) Arbitration Process Any disagreement that may arise on scientific/programmatic matters (within the scope of the award), between award recipients and the NHGRI may be brought to arbitration. An Arbitration Panel, whose composition is described in the Definitions (above) will be convened. This special arbitration procedure in no way affects the awardee"s right to appeal an adverse action that is otherwise appealable in accordance with NIH regulations 42 CFR Part 50, Subpart D and HHS regulation at 45 CFR Part 16. (7) Yearly Milestones All awardees participating in the BAC library-making program will be asked to define yearly milestones at the time of the award and to update these milestones annually at the anniversary date. These will be made a condition of the award. In accord with the procedures described above, NHGRI may withhold or reduce funds for any project that substantially fails to meet its milestones or to maintain the state of the art. 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 sub-populations must be included in all NIH-supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification are provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing 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 is 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: o 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 o all investigators to report accrual, and to conduct and report analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. 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. LETTER OF INTENT Prospective applicants are asked to submit 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 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 IC staff to estimate the potential review workload and plan the review. The letter of intent should be sent by June 1, 2001 to: Dr. Jane L. Peterson Program Director, Large Scale Sequencing National Human Genome Research Institute National Institutes of Health Building 31, Room B2B07, MSC2033 Bethesda, MD 20892-2033 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, MSC 7910, Bethesda, MD 20892-7910, 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. The sample RFA label available at: http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to allow for this change. Please note this is in pdf format. 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 the time of submission, two additional copies of the application must be sent to: Dr. Rudy Pozzatti Scientific Review Administrator Office of Scientific Review Building 31, Room B2B37, MSC 2032 National Human Genome Research Institute National Institutes of Health Bethesda, MD 20982-2032 Telephone: (301) 402-0838 Applications must be received by June 27, 2001. 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 the CSR and responsiveness by the NHGRI. Incomplete and/or non-responsive applications will be returned to the applicant without further consideration. Applications that are complete and responsive to RFA HG-01-002 will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NHGRI 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 National Advisory Council for Human Genome Research and the National Advisory Research Resources Council. Review Criteria The application must be directed toward attaining the programmatic goals as stated under RESEARCH OBJECTIVES AND SCOPE. The following criteria will be used by peer review groups to evaluate these applications: o Significance: Does the proposal address the problem outlined in this RFA? o Approach: Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, and appropriate to the aims of the project and as outlined in this RFA? Does the applicant identify potential problem areas and consider reasonable solutions? Is the proposed effort likely to produce an adequate number of high quality, quality controlled BAC libraries during the term of an award? Are the plans for data and library dissemination appropriate? o Innovation: Does the project employ novel concepts, approaches or method to improve the scientific utility of BAC libraries? to reduce the costs, or increase the efficiency of constructing BAC libraries? o Data release and library dissemination: Are the plans for data release and library dissemination appropriate? o 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)? o 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, in accordance with NIH policy, 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. Schedule Letter of Intent Receipt Date: June 1, 2001 Application Receipt Date: June 27, 2001 Peer Review Date: early August, 2001 Council Review: September 10-11 , 2001 Earliest Anticipated Start Date: December 1, 2001 AWARD CRITERIA Awards will be made on the basis of scientific and technical merit as determined by peer review, programmatic needs and balance, availability of funds and: o Likelihood that the proposed program will make a significant contribution toward meeting the research community"s need for BAC libraries. o Cost effectiveness of the proposed BAC library production effort. o Likelihood that any proposed technology development effort will lead to significant improvement in the scientific quality of BAC libraries and/or to a reduction in the cost of generating BAC libraries. INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or answer questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Dr. Jane L. Peterson Division of Extramural Research National Human Genome Research Institute National Institutes of Health Building 31, Room B2B07 MSC 2033 Bethesda, MD 20892-2033 Telephone: (301) 496-7531 FAX: (301) 480-2770 E-mail: Jane_Peterson@nih.gov John D. Harding, Ph.D. Division of Comparative Medicine National Center for Research Resources 6705 Rockledge Drive, Suite 6050, MSC 7965 Bethesda, MD 20892-7965 Telephone: (301) 435-0776 FAX: (301) 480-3819 E-mail: hardingj@ncrr.nih.gov Direct inquiries regarding review issues to: Dr. Rudy Pozzatti Scientific Review Administrator Office of Scientific Review National Human Genome Research Institute National Institutes of Health Building 31, Room B2B37, MSC 2032 Bethesda, MD 20982-2032 Telephone: (301) 402-0838 FAX: (301) 435-1580 E-mail: Rudy_Pozzatti@nih.gov Direct inquiries regarding fiscal matters to: Ms. Jean Cahill Grants Administration Branch National Human Genome Research Institute Building 31, Room B2B34, MSC 2031 Bethesda, MD 20892-2031 Telephone: (301) 402-0733 FAX: (301) 402-1951 E-mail: Jean_Cahill@nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.172, (use appropriate program number). 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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