Vol. 18, No. 2, January 20, 1989 NOTICES EXTRAMURAL RESEARCHERS' FINANCIAL CONFLICTS OF INTEREST ...(84/126)......... 1 National Institutes of Health Index: NATIONAL INSTITUTES OF HEALTH DATED ANNOUNCEMENTS (RFPs AND RFAs) ANALYTICAL CHEMISTRY OF CHEMICALS AND PHARMACEUTICAL PRODUCTS FOR TREATMENT OF INFECTIOUS DISEASES (RFP) ................(132/175)........ 1 National Institute of Allergy and Infectious Diseases Index: ALLERGY, INFECTIOUS DISEASES DEVELOPMENT AND MANUFACTURE OF DOSAGE FORMS OF COMPOUNDS WITH POTENTIAL FOR TREATING INFECTIOUS DISEASES (RFP) ..........(178/221)........ 2 National Institute of Allergy and Infectious Diseases Index: ALLERGY, INFECTIOUS DISEASES NOTICE - SURVEILLANCE EPIDEMIOLOGY AND END RESULTS (SEER) (RFP) ..(224/264). 2 National Cancer Institute Index: CANCER ACADEMIC RESEARCH ENHANCEMENT AWARD ........................(267/370)....... 3 National Institutes of Health Index: NATIONAL INSTITUTES OF HEALTH CORE GRANTS FOR CLINICAL NUTRITION RESEARCH UNITS (CNRUs) (RFA) ..(373/473). 4 National Institute of Diabetes and Digestive and Kidney Diseases (804/913) National Institute on Aging Index: DIABETES, DIGESTIVE AND KIDNEY DISEASES, AGING MENTAL HEALTH SERVICES RESEARCH DEMONSTRATION GRANTS (RFA) ...(481/519)..... 6 National Institute of Mental Health Index: MENTAL HEALTH NEW APPROACHES TO STUDYING EPSTEIN-BARR VIRUS ONCOGENESIS (RFA) ..(522/655). 6 National Cancer Institute (916/1248) Index: CANCER DEVELOPMENT OF SOMATIC CELL GENE THERAPY APPROACHES FOR SPECIFIC INBORN METABOLIC DISEASES (RFA) ....................(658/789, 1251/1473).... 8 National Institute of Diabetes and Digestive and Kidney Diseases Index: DIABETES, DIGESTIVE AND KIDNEY DISEASES NOTICES EXTRAMURAL RESEARCHERS' FINANCIAL CONFLICTS OF INTEREST P.T. 34; K.W. 1014004, 1014006 National Institutes of Health Growing expressions of public concerns suggest that NIH act to limit possibilities for actual or apparent financial conflicts of interest by investigators in research and development projects funded by NIH extramural awards. Of particular concern are circumstances that might affect investigators' objectivity, or where researchers might unduly influence, or might be perceived to influence, NIH-funded R&D projects in directions favorable to personal financial interests of themselves, their spouses, children, close professional associates, or organizations where they have appointments or other relationships. NIH expects that participating investigators and consultants will not have financial interests in organizations or entities that produce drugs, devices, or other interventions studied in a controlled clinical trial. NIH therefore intends to take steps to develop appropriate guidance for such relationships. Guidelines would seek to outline pertinent types of research situations and personal financial interests, in accord with the PHS Grants Policy Statement, January 1, 1987, revision, concerning Standards of Conduct for Employees for awardee organizations, and to define appropriate distributions of governance between NIH and awardee organizations. Guidelines should also recognize special conditions under which restrictions should be waived to permit investigators with unusual skills and expertise to conduct studies which might otherwise be proscribed. (These guidelines should not concern financial benefits resulting from logical steps in product research/development/testing under NIH awards, e.g., Small Business Innovation Research.) NIH encourages preliminary comments from parties wishing to suggest points to be included in this future guidance. Please address your remarks within 30 days of this publication to: Dr. Katherine L. Bick Deputy Director for Extramural Research National Institutes of Health Shannon Building, Room 144 Bethesda, Maryland 20892 Further opportunity for comments will be provided following subsequent notices in the NIH Guide for Grants and Contracts. DATED ANNOUNCEMENTS (RFPs AND RFAs) ANALYTICAL CHEMISTRY OF CHEMICALS AND PHARMACEUTICAL PRODUCTS FOR TREATMENT OF INFECTIOUS DISEASES RFP AVAILABLE: RFP-NIH-NIAID-AIDSP 89-14 P.T. 34; K.W. 1003008, 0740025 National Institute of Allergy and Infectious Diseases The purpose of the solicitation is to provide analytical chemistry support to the drug discovery effort for the treatment of infectious diseases in the areas of method development and control of chemical and pharmaceutical quality. Responsibilities of the contractor will include: characterization of the identity of the drug substance; preformulation determinations of compound solubility and stability; analysis of pharmaceutical dosage forms; and extensions of the methodologies to the detection of the drug in selected biological fluids. This announcement is a new solicitation. The issuance of the RFP will be on January 26, 1989, and proposals will be due COB on March 29, 1989. This NIAID-sponsored project will take approximately five years to complete. A cost-reimbursement contract is anticipated and the Institute expects to make one award. Vol. 18, No. 2, January 20, 1989 - Page 1 Requests for the RFP should be directed in writing to: Mr. Charles Hayes Contract Management Branch Westwood Building, 5333 Westbard Avenue, Room 707 National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda, Maryland 20892 Telephone: (301) 496-0349 To receive a copy of the RFP, please supply this office with two (2) self-addressed mailing labels. All responsible sources may submit a proposal which will be considered. This advertisement does not commit the Government to award a contract. DEVELOPMENT AND MANUFACTURE OF DOSAGE FORMS OF COMPOUNDS WITH POTENTIAL FOR TREATING INFECTIOUS DISEASES RFP AVAILABLE: RFP-NIH-NIAID-AIDSP-89-12 P.T. 34; K.W. 0740025, 0740020 National Institute of Allergy and Infectious Diseases The purpose of this solicitation is to provide a pharmaceutical research and development capability to permit further evaluation of compounds in animal models of infectious diseases, in pharmacological disposition studies in laboratory animals, in toxicological investigations and in clinical trial. Dosage form development and manufacturing capabilities will be needed for sterile small volume parenteral freeze dried and liquid dosage forms, tablets, and capsules. Quality control testing of ingredients in the formulation and of the final product will be required. Manufactured batches will be prepared in accord with FDA's current good manufacturing practice regulations. Anticipated annual requirements are one or two drugs requiring development of injectable and of oral dosage forms, one or two injectable batches of about 4000 vials each, and two of three table/capsule batches of 50,000 units/lot. This announcement is a new solicitation. The issuance of the RFP will be on January 25, 1989, and proposals will be due COB March 28, 1989. This NIAID sponsored project will take approximately five years to complete. A cost-reimbursement contract is anticipated and the Institute expects to make one award. Requests for the RFP should be directed in writing to: Ms. Mary Anne Glitz Contract Management Branch Westwood Building, 5333 Westbard Avenue, Room 707 National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda, Maryland 20892 Telephone: (301) 496-1642 To receive a copy of the RFP, please supply this office with two (2) self-addressed mailing labels. All responsible sources may submit a proposal which will be considered. This advertisement does not commit the Government to award a contract. NOTICE - SURVEILLANCE EPIDEMIOLOGY AND END RESULTS (SEER) NCI-CN-95112, NCI-CN-95113, NCI-CN-95114, NCI-CN-95115, NCI-CN-95116, NCI-CN-95117, NCI-CN-95118, NCI-CN-95119, NCI-CN-95120, NCI-CN-95121, NCI-CN-95122 P.T. 34; K.W. 0785055, 0755018, 0715035 National Cancer Institute The Division of Cancer Prevention and Control, National Cancer Institute, intends to negotiate with the Connecticut Department of Health Services, the Commonwealth of Puerto Rico Department of Health, Emory University, Fred Hutchinson Cancer Research Center, Michigan Cancer Foundation, New Jersey Dept. of Health, Northern California Cancer Center, Research Corporation of Vol. 18, No. 2, January 20, 1989 - Page 2 the University of Hawaii, University of Iowa, University of New Mexico, and the University of Utah for a seven-year continuation contract for the Surveillance, Epidemiology and End Results (SEER) Program. The project includes collecting and reporting on population-based cancer incidence, treatment and survival data for the United States. (Authority: 41 U.S.C. 253 (c) (1), as set forth in FAR 6.302-1 and HHSAR 306.302.-1.) Only one responsible source and no other supplies or services will satisfy agency requirements. In accordance with FAR 6.302-1 (a) (2) (ii) and HHSAR 306.302(a) (2) (ii), services may be deemed to be available only from the original sources for follow-on contracts for continued development. Inherent duplication of cost to the Government and unacceptable delays in completing this follow-up project make competition unfeasible for this project. The above named organizations have the prerequisite knowledge, experience and facilities for continued performance of the proposed tasks by virtue of their preliminary and current work on these projects. For Informational Purposes Only. RFP is not available. For further information contact: Shirley Kyle Contracting Officer Prevention and Cancer Control Section, RCB National Cancer Institute, NIH Executive Plaza South, Suite 635 Bethesda, Maryland 20892 Telephone: (301) 496-8603 ACADEMIC RESEARCH ENHANCEMENT AWARD P.T. 34; K.W. 0710030, 1014002, 1014006 National Institutes of Health Application Receipt Date: June 22, 1989 The National Institutes of Health (NIH) is making a special effort to stimulate research in educational institutions which provide the baccalaureate training for a significant number of our nation's research scientists but which historically have not been major recipients of NIH support. Since Fiscal Year (FY) 1985, Congressional appropriations for the NIH have included funds for this initiative, which NIH has implemented through the Academic Research Enhancement Award (AREA) Program. In FY 85, the NIH made 75 awards, totalling $5 million. In FY 86, 146 such grants were awarded, amounting to $9.57 million. In FY 87, a total of 152 AREA grants were awarded from the Congressional appropriation of $10 million. In FY 88, 173 awards were made, totalling approximately $11 million. This award is designed to enhance the research environment of educational institutions that have not been traditional recipients of NIH research funds. The AREA funds are intended to support new research projects or expand ongoing research activities proposed by faculty members of these institutions in areas related to the health sciences. Applications for FY 1989 AREA grants are currently undergoing review for scientific merit. Since it is anticipated that additional funds will be available next year, the NIH is inviting grant applications for the FY 1990 competition for AREA grants. Eligibility requirements of the AREA Program include the following: Applicant Institutions o All domestic institutions offering baccalaureate or advanced degrees in the sciences related to health are eligible, except those that have received an NIH Biomedical Research Support Grant (BRSG) of $20,000 or more per year for four or more years during the period from FY 1982 through FY 1988. o Health professional schools (e.g., schools of medicine, dentistry, nursing, osteopathy, pharmacy, veterinary medicine, public health, allied health and optometry) as well as organizationally discrete campuses of a university system are eligible if they meet the above criterion. o Multiple applications proposing different research projects may be submitted by an applicant institution. Applicant Principal Investigators o Must not have active research grant support (including an AREA) from either NIH or the Alcohol, Drug Abuse and Mental Health Administration (ADAMHA) at the applicant institution at the time of award of an AREA grant. Vol. 18, No. 2, January 20, 1989 - Page 3 o May not submit a regular NIH or ADAMHA research grant application for essentially the same project as a pending AREA application. o Are expected to conduct the majority of their research at their own institution, although limited access to special facilities or equipment at another institution is permitted. o May not be awarded more than one AREA grant at a time nor be awarded a second AREA grant to continue the research initiated under the first AREA grant. Those in doubt about eligibility should consult their institution's Office of Sponsored Research, or the Director, Special Programs and Initiatives (Building 31, Room 1B54, NIH, Bethesda, MD 20892, 301/496-1968). Funding decisions will be based on the proposed research project's scientific merit and relevance to NIH programs, and the institution's contribution to the undergraduate preparation of doctoral-level health professionals. Among projects of essentially equivalent scientific merit and program relevance, preference will be given to those submitted by institutions that have granted baccalaureate degrees to 25 or more individuals who, during the period 1978-1988, obtained academic or professional doctoral degrees in the health related sciences. AREAs are awarded on a competitive basis. Applicants may request support for up to a total of $75,000 in direct costs (plus applicable indirect costs) for a period not to exceed 36 months. Although this award is non-renewable, it will enable qualified individual scientists within the eligible institutions to receive support for feasibility studies, pilot studies and other small-scale research projects preparatory to seeking more substantial funding from the regular NIH research grant programs. Applications for this award will be accepted under the regular application submission procedures of the Division of Research Grants (DRG) of NIH. Grant applications must be prepared and submitted on Form PHS 398 (Rev. 9/86). An abbreviated format and simplified instructions will be provided upon request to the Office of Grants Inquiries (see address below) for use in preparing these applications. The receipt date is June 22, 1989. Those individuals and institutions meeting eligibility requirements and wishing to receive further information and/or application materials should write to: AREA Office of Grants Inquiries Division of Research Grants National Institutes of Health Westwood Building, Room 449 Bethesda, Maryland 20892 Telephone: (301) 496-7441 CORE GRANTS FOR CLINICAL NUTRITION RESEARCH UNITS (CNRUs) RFA AVAILABLE: 89-DK-02 P.T. 34; K.W. 0710095, 0710030 National Institute of Diabetes and Digestive and Kidney Diseases National Institute on Aging Application Receipt Date: April 12, 1989 The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institute on Aging (NIA) invite applications for Clinical Nutrition Research Unit (CNRU) grants to be awarded in Fiscal Year 1990. The award of up to two CNRU grants is anticipated in Fiscal Year 1990. A CNRU is an integrated array of research, educational, and service activities that is oriented toward human nutrition in health and disease. A research core center grant is awarded to facilitate the planning and coordination of the activities of the CNRU primarily by providing funding for core facilities and associated staff that serve the various projects of the CNRU on a shared basis. Vol. 18, No. 2, January 20, 1989 - Page 4 ESSENTIAL COMPONENTS OF A CNRU A CNRU, at a minimum, must comprise the following seven components which also should have other sources of support such as a regular NIH research grant (RO1), NIH FIRST Award (R29), NIH Program Project (PO1), NIH Individual Fellowship (F32), and the NIH Institutional National Research Service Award (T32) or other Federal and non-federal sources: 1. Research with human subjects and populations; 2. Laboratory investigations; 3. Research training (funds to be derived from other sources*); 4. Shared facilities and research services; 5. Education programs for medical students, house staff, practicing physicians, and allied health personnel (funds to be derived from other sources*); 6. Research components of nutritional support services; and 7. Public information activities (funds to be derived from other sources*). * Funds to support these components may not be requested as part of an application in response to this announcement. Potential applicants are urged to submit a letter of intent that provides a descriptive title, names of investigators involved and other participating institutions regarding their application. The letter of intent is non-binding and is not a precondition for an award and should be submitted by February 15, 1989, to Dr. Bain at the address below. In addition, the general description of a Core Center, copies of Core Center Guidelines, a more detailed RFA and consultation may be obtained from: Van S. Hubbard, M.D., Ph.D. Ralph L. Bain, Ph.D. Director, Clinical Nutrition Program Director for Digestive Research Units Diseases Centers Program and Westwood Building, Room 3A18B Assistant Program Director for CNRU 5333 Westbard Avenue Westwood Building, Room 3A16 Bethesda, Maryland 20892 5333 Westbard Avenue Telephone: (301) 496-7823 Bethesda, Maryland 20892 Telephone: (301) 496-6045 For information concerning NIA research interests in nutrition contact: Ann Sorenson, Ph.D. Program Director for the NIA Nutrition Program Building 31, Room 5C-21 9000 Rockville Pike Bethesda, Maryland 20892 Telephone: (301) 496-1033 Applications for the CNRU Core Center grant will be evaluated in national competition by the NIH grant peer review process. The receipt of two competitive continuation applications is anticipated. Applications will be reviewed initially by a special review committee convened by the NIDDK and subsequently by the National Diabetes and Digestive and Kidney Diseases Advisory Council and/or the National Institute on Aging's Advisory Council. The special single receipt date for submissions in response to this announcement is April 12, 1989, with earliest funding December 1989. Applications are unlikely to be reviewed by a site visit team; therefore, the written application should be complete so as to facilitate review without a site visit. Extensive additional material submitted subsequent to the stated receipt date will not be accepted. The RFA label available in the 9/86 revision of Application Form 398 must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of your application such that it may not reach the review committee in time for review. Complete line 2 of the application face page with the title of this RFA, "Core Grants for Clinical Nutrition Research Units (CNRUs)," and the RFA number 89-DK-02. Vol. 18, No. 2, January 20, 1989 - Page 5 MENTAL HEALTH SERVICES RESEARCH DEMONSTRATION GRANTS (COMMUNITY SUPPORT PROGRAM FOR ADULTS) RFA AVAILABLE: MH-88-11 P.T. 34; K.W. 0715095, 0403004 National Institute of Mental Health Application Receipt Date: April 10, 1989 The National Institute of Mental Health (NIMH) requests applications for research demonstration grants to evaluate the effectiveness and generalizability of various approaches to case management services, community crisis-response services, and psychiatric rehabilitaton services. The purpose is to generate new knowledge on effective, replicable approaches to providing the three service components and to begin building the infrastructure required to conduct future systematic research on community support services. Only State mental health authorities are eligible to apply; they may submit only one application for one project under this RFA. In 1989, it is estimated that the community support program will fund a total of approximately 8-12 projects averaging $250-350,000 per year in the three service areas. NIMH will accept applications in response to this RFA under the receipt date of April 10, 1989. Potential applicants wishing to seek further information should contact: Neil Brown, Chief, Community Support and Advocacy Branch or Jacqueline Parrish, Program Director Community Support Program Division of Education and Service Systems Liaison National Institute of Mental Health Parklawn Bulding, Room 11C-22 5600 Fishers Lane Rockville, Maryland 20857 Telephone: (301) 443-3653 NEW APPROACHES TO STUDYING EPSTEIN-BARR VIRUS ONCOGENESIS RFA AVAILABLE: 89-CA-08 P.T. 34; K.W. 0715035, 0715125, 1002045, 1002008, 0760045 National Cancer Institute Application Receipt Date: August 3, 1989 Letter of Intent Receipt Date: June 3, 1989 I. INTRODUCTION Epstein-Barr virus (EBV) has been associated with several neoplasias, including Burkitt's lymphoma and nasopharyngeal carcinoma and with several infectious diseases, including infectious mononucleosis and severe chronic infectious mononucleosis. Recent evidence appears to link EBV with parotid gland tumors and B-cell lymphomas in immunosuppressed individuals. In vivo studies of EBV oncogenesis are complicated by the long interval between primary infection and the occurrence of neoplasia; and by the high prevalence of EBV infection in geographic areas where a high frequency of EBV-associated neoplasias occurs: e.g., in the malaria belt in Africa in the case of Burkitt's lymphoma, and in the Far East in the case of nasopharyngeal carcinoma. In vitro studies of EBV have been hampered by the lack of a lytic infection system. Studies have focused on lymphocytes which have been immortalized/transformed by EBV infection and in which a limited set of viral gene products are expressed. The application of recombinant DNA technology to this system has led to progress in elucidating the structure of the viral genome, further definition of viral gene products, and identification of several regulatory regions of the viral genome. However, the viral and host factors determining the disease manifestations and clinical outcomes for EBV infections are as yet undefined. Additionally, both B-cells and epithelial cells appear to be sites of viral latency and replication. While a number of investigators are studying specific aspects of EBV replication and tumorigenesis, delineation of viral and host factors which may determine the outcome of individual EBV infections has been difficult to approach directly. Vol. 18, No. 2, January 20, 1989 - Page 6 The present RFA is for a single competition with a deadline of August 3, 1989 for receipt of applications, and June 3, 1989 for receipt of letters of intent. Applications should be prepared and submitted in accordance with the aims and requirements described in the complete RFA document which may be obtained from the program director listed in Section IV below. II. RESEARCH GOALS AND SCOPE The overall thrust of this RFA is to stimulate research on the mechanism(s) of EBV oncogenesis by developing and using new methodological approaches to overcome the difficulties inherent in EBV research. Examples of research objectives (which are not all inclusive) would include the following: (i) use of novel methods and probes to define RNA transcripts unique to or with clinical significance for different EBV neoplasias; (ii) use of new approaches to alter (mutate) the viral genome followed by the study of the effect of altered genes on viral oncogenesis; (iii) use of cell lines expressing individual EBV gene products (both structural and regulatory) to define viral genes and assess their role in the neoplastic process; (iv) use of specific reagents such as monoclonal antibodies to viral gene products to determine the role of regulatory and structural EBV proteins in the neoplastic process; (v) measurement of host response to individual viral proteins with the goal of delineating differences in the host response in specific EBV-associated neoplasias; (vi) delineation of differences in cell-mediated responses in individuals with different EBV neoplasias; and (vii) exploitation of EBV's unique pathologic aspects, such as the use of the CR-2 receptor and the activation of B-cells during the infectious process, to develop approaches to alter these unique aspects of EBV pathogenesis with the ultimate aim of preventing or reversing neoplastic conversion. Where appropriate, collaborative arrangements to facilitate the achievement of research goals should be considered. Applications should contain as goals both methodological development and application to a specific area of EBV oncogenesis; basic and/or clinical issues are considered as appropriate subjects for this RFA. Furthermore, in studies involving differences between various EBV-associated neoplasias, investigators should consider not only the classical EBV-associated neoplasias, such as Burkitt's lymphoma and nasopharyngeal carcinoma, but also give some emphasis to newer EBV-related neoplasias such as EBV lymphomas in immunocompromised individuals, EBV tumors in other areas of the oropharynx such as the parotid gland, and other new EBV-associated diseases such as hairy leukoplakia. III. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) grant-in-aid. Responsibility for the planning, direction and execution of the proposed project will be solely that of the applicant. Except as stated in this RFA, awards will be administered under PHS grants policy as stated in the Public Health Service Grants Policy Statement, DHHS Publication No. (OASH) 82-50,000, revised January 1, 1987. This RFA is a one-time solicitation. Generally future unsolicited competing renewal applications will compete as research project applications with all other investigator-initiated applications and be reviewed in a standing Division of Research Grants study section. However, should the NCI determine that there is a sufficient continuing program need, NCI may announce a request for renewal applications. Approximately $ 850,000 in total costs per year for five (5) years will be committed to specifically fund applications which are submitted in response to this RFA. It is anticipated that four (4) to five (5) awards will be made. This funding level is dependent on the receipt of a sufficient number of applications of high scientific merit. The total project period for applications submitted in response to the present RFA should not exceed five (5) years. The earliest feasible start date for the initial awards will be April 1, 1989. Although this program is provided for in the financial plans of the National Cancer Institute (NCI), award of grants pursuant to this RFA is also contingent upon the availability of funds for this purpose. Non-profit and for-profit institutions are eligible to apply. Foreign as well as domestic institutions are eligible. IV. INQUIRIES A copy of the complete RFA describing the research goals and scope, the review criteria, and the method of applying can be obtained by contacting: Vol. 18, No. 2, January 20, 1989 - Page 7 Dr. Susan B. Spring Program Director DNA Virus Studies I Biological Carcinogenesis Branch Division of Cancer Etiology National Cancer Institute Executive Plaza North, Room 540 Bethesda, Maryland 20892 Telephone: (301) 496-4533 Written or telephone inquiries concerning the objectives and scope of this RFA or inquiries about whether or not specific proposed research would be responsive are encouraged and should be directed to Dr. Susan B. Spring at the above address. The program director welcomes the opportunity to clarify any issues or questions from potential applicants. DEVELOPMENT OF SOMATIC CELL GENE THERAPY APPROACHES FOR SPECIFIC INBORN METABOLIC DISEASES RFA AVAILABLE: 89-DK-04 P.T. 34; K.W. 0715135, 1002058, 0780015, 0755020 National Institute of Diabetes and Digestive and Kidney Diseases Application Receipt Date: July 15, 1989 INTRODUCTION AND BACKGROUND The Metabolic Diseases and the Cystic Fibrosis Research Programs, Division of Diabetes, Endocrinology and Metabolic Diseases, support basic and clinical research and research training related to the etiology, diagnosis, prevention and treatment of inborn metabolic diseases such as: cystic fibrosis (CF), other diseases of transport, aminoacidemias, organic acidurias, lysosomal storage diseases, diseases of purine and pyrimidine metabolism, glycogen storage diseases, diseases of copper metabolism, hereditary amyloidosis, etc. This initiative is an important component of a broad program for the development or improvement of therapies for orphan diseases. This initiative is intended to encourage qualified scientists to submit regular research project grant (R01) or program project grant (P01) applications which propose novel studies to facilitate development of approaches to somatic cell gene therapy. For the purposes of this program gene therapy is defined as a molecular genetic therapeutic approach that utilizes somatic cell gene transfer to correct or ameliorate the inborn error. OBJECTIVES AND SCOPE This program is intended to encourage submission of proposals to develop approaches to human gene therapy for inborn metabolic diseases. Areas of research include but are not limited to the following: development of more efficient and more rapid approaches to chromosomal localization of relevant genes; identification and characterization of retroviral and other vectors suitable for gene transfection; development of efficient gene transfection techniques; development of techniques for homologous recombination of transfected gene/s and the host chromosome in cells, or mice or other animals that serve as models for specific metabolic diseases; development of cell lines and/or mouse models suitable for gene therapy studies; development of techniques for isolation and maintenance of host cells suitable for gene therapy; and introduction of the transfected cell into the relevant target organs of an animal model and the study of in vivo expression of the functional protein. This program is intended to stimulate basic research and development of techniques focused on achieving successful human gene therapy. In this regard, studies on the general mechanisms of recombination and transfection are not suitable. MECHANISM OF SUPPORT The mechanism of support for this program will be the grant-in-aid (R01) and the program project grant (P01). Although this solicitation is included in the funding plans for Fiscal Year 1990 for NIDDK, support is contingent upon actual availability of appropriated funds. The NIDDK plans to designate a total of $2.0 million (direct and indirect costs) for the support of applications submitted in response to this solicitation; however, the amounts to be awarded will depend upon the overall merit, budget, and scope of the Vol. 18, No. 2, January 20, 1989 - Page 8 applications received. It is anticipated that approximately 5 to 10 grants will be awarded under this solicitation. APPLICATION AND REVIEW PROCEDURES Applications must be submitted on Form PHS 398 (revised 9/86), available at most institutional business offices or from the Division of Research Grants, NIH. To identify the application as a response to this RFA, please check "Yes" on item two of page one of the application and enter "NIDDK-RFA-89-DK-04 on "Somatic Cell Gene Therapy Approaches". The RFA label (found in the 9/86 revision of application form PHS 398) must be affixed to the bottom of the face page of the orginal copy of the application. Applications received in response to this solicitation will be reviewed in accord with the usual NIH peer review procedures. It is expected that site visits will not be conducted and therefore the submitted applications should be complete and stand alone for purposes of review. If an application submitted in reponse to this RFA is identical to a research grant application already submitted to the NIH for review, the applicant will be asked to withdraw the pending application before the new one is accepted. Simultaneous submission of identical applications will not be allowed. Both a P01 application and the projects which are components of this P01 may not be submitted simultaneously in response to this RFA. A single reply date of July 15, 1989, will be strictly enforced. An anticipated schedule for review and award is detailed below: APPLICATION INITIAL COUNCIL EARLIEST RECEIPT REVIEW REVIEW START DATE July 15, 1989 Oct/Nov 1989 Feb. 1990 April 1990 The original and four copies of the application should be sent to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, Maryland 20892** Two additional copies of the application are to be sent to: Review Branch National Institute of Diabetes and Digestive and Kidney Diseases, NIH Westwood Building, Room 406 Bethesda, Maryland 20892 CONSULTATION WITH PROGRAM STAFF Prospective applicants are encouraged to request a copy of the complete RFA and to discuss their ideas with Program staff (see below) to determine whether they fit guidelines of this RFA. Applicants who intend to submit P01 applications should request a copy of NIDDK's guidelines for program project grants. Robert Katz, Ph.D. Nancy Lamontagne, Ph.D. Director, Metabolic Diseases Director, Cystic Fibrosis Research Program, NIDDK Program, NIDDK Westwood Building, Room 607A Westwood Building, Room 607 Bethesda, Maryland 20892 Bethesda, Maryland 20892 Telephone: (301) 496-7997 Telephone: (301) 496-4980 This program is described in the Catalog of Federal Domestic Assistance, No.13.847, Diabetes, Endocrinology, and Metabolic Diseases. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301, (Public Law 78-410), as amended; 42 USC 241) and administered under PHS grant policies and Federal Regulations, most specifically at 42 CFR Part 52 and CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. **THE MAILING ADDRESS GIVEN FOR SENDING APPLICATIONS TO THE DIVISION OF RESEARCH GRANTS OR CONTACTING PROGRAM STAFF IN THE WESTWOOD BUILDING IS THE CENTRAL MAILING ADDRESS FOR THE NATIONAL INSTITUTES OF HEALTH. APPLICANTS WHO USE EXPRESS MAIL OR A COURIER SERVICE ARE ADVISED TO FOLLOW THE CARRIER'S REQUIREMENTS FOR SHOWING A STREET ADDRESS. THE ADDRESS FOR THE WESTWOOD BUILDING IS: 5333 Westbard Avenue Bethesda, Maryland 20816 Vol. 18, No. 2, January 20, 1989 - Page 9 FULL TEXT OF RFAs FOR ONLINE ACCESS CORE GRANTS FOR CLINICAL NUTRITION RESEARCH UNITS (CNRUS) RFA AVAILABLE: 89-DK-02 P.T. 34; K.W. 0710095, 0710030 NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES NATIONAL INSTITUTE ON AGING Application Receipt Date: April 12, 1989 The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institute on Aging (NIA) invite applications for Clinical Nutrition Research Unit (CNRU) grants to be awarded in Fiscal Year 1990. The award of up to two CNRU grants is anticipated in Fiscal Year 1990. A CNRU is an integrated array of research, educational, and service activities that is oriented toward human nutrition in health and disease. A research core center grant is awarded to facilitate the planning and coordination of the activities of the CNRU primarily by providing funding for core facilities and associated staff that serve the various projects of the CNRU on a shared basis. The Core Center is a mechanism designed to enhance and extend the effectiveness of a group of related projects and investigators that are already funded through other mechanisms such as Research Project Grants or Research Program Projects. In this respect, the Core Center mechanism builds upon an established base of research excellence which emphasizes common themes or foci. The Core Center Grant may provide funds for: (1) core units such as trace mineral analyses, lipid analyses or isotope analyses. These facilities must be utilized by two or more center participants who are already funded; (2) pilot/feasibility projects which encourage new investigators or investigators from other fields to pursue new innovative ideas to a point where they can compete for independent support; (3) temporary salary support to one new named investigator, usually for 24 months, in specified areas of research complementary to ongoing activities of the group and with an approved pilot/feasibility project; (4) program enrichment funds to provide for small conferences or symposia, advisory committee expenses and special consultants. The objectives of the Core Center are to encourage a multidisciplinary approach to clinical nutrition research and to bring together, on a cooperative basis, clinical and basic science investigators in a manner which will enhance and extend the effectiveness of research being conducted in the field of nutritional sciences. An average Center may include about 5 to 7 pilot/feasibility projects and 4-6 core units with a total cost of approximately $500,000. However, the actual cost of the Center will vary depending on the needs of the Center. The anticipated award(s) will be for 5 years and is contingent upon the availability of appropriated funds. Potential applicants are urged to submit a letter of intent that provides a descriptive title, names of investigators involved and other participating institutions regarding their application. The letter of intent is non-binding and is not a precondition for an award and should be submitted by February 15, 1989, to Dr. Bain at the address below. In addition, the general description of a Core Center, copies of Core Center Guidelines and consultation may be obtained from: Van S. Hubbard, M.D., Ph.D. Ralph L. Bain, Ph.D. Director, Clinical Nutrition Program Director for Digestive Research Units Program Diseases Centers Program and Westwood Building, Room 3A18B Assistant Program Director for CNRU 5333 Westbard Avenue Westwood Building, Room 3A15B Bethesda, Maryland 20892 5333 Westbard Avenue Telephone: (301) 496-7823 Bethesda, Maryland 20892 Telephone: (301) 496-6045 For information concerning the NIA research interest in nutrition contact: Ann Sorenson, Ph.D. Program Director for the NIA Nutrition Program Building 31, Room 5C-21 9000 Rockville Pike Bethesda, Maryland 20892 Telephone: (301) 496-1033 Applications for the CNRU Core Center grant will be evaluated in national competition by the NIH grant peer review process. The receipt of two competitive continuation applications is anticipated along with other applications. Applications will be reviewed initially by a special review committee convened by the NIDDK and subsequently by the National Diabetes and Digestive and Kidney Diseases Advisory Council and/or the National Institute on Aging's Advisory Council. The special single receipt date for submissions in response to this announcement is April 12, 1989 with earliest funding December 1989. Applications are unlikely to be reviewed by a site visit team; therefore, the written application should be complete so as to facilitate review without a site visit. Extensive additional material submitted subsequent to the stated receipt date will not be accepted. The RFA label (found in the 9/86 revision of application form PHS 398) must be affixed to the bottom of the face page of the original copy of the application. Failure to use this label could result in delayed processing of an application such that it may not reach the review committee in time for a review. Complete line 2 of the application face page with the title of this RFA, "Core Grants for Clinical Nutrition Research Units (CNRUs)," and the RFA number 89-DK-02. Two copies of the application are to be sent to: Review Branch NIDDK 5333 Westbard Avenue Westwood Building, Room 406 Bethesda, Maryland 20892 Four copies of the application are to be sent to the address on the mailing label in the application kit. RFA NUMBER: 89-CA-08 RFA TITLE: New Approaches to Studying Epstein-Barr Virus Oncogenesis P.T. 34; K.W. 0715035, 0715125, 1002045, 1002008, 0760045 NATIONAL CANCER INSTITUTE APPLICATION RECEIPT DATE: August 3, 1989 LETTER OF INTENT RECEIPT DATE: June 3, 1989 I. INTRODUCTION Epstein-Barr virus (EBV) has been associated with several neoplasias, including Burkitt's lymphoma and nasopharyngeal carcinoma and with several infectious diseases, including infectious mononucleosis and severe chronic infectious mononucleosis. Recent evidence appears to link EBV with parotid gland tumors and B-cell lymphomas in immunosuppressed individuals. In vivo studies of EBV oncogenesis are complicated by the long interval between primary infection and the occurrence of neoplasia; and by the high prevalence of EBV infection in geographic areas where a high frequency of EBV-associated neoplasias occurs: e.g., in the malaria belt in Africa in the case of Burkitt's lymphoma, and in the Far East in the case of nasopharyngeal carcinoma. In vitro studies of EBV have been hampered by the lack of a lytic infection system. Studies have focused on lymphocytes which have been immortalized/transformed by EBV infection and in which a limited set of viral gene products are expressed. The application of recombinant DNA technology to this system has led to progress in elucidating the structure of the viral genome, further definition of viral gene products, and identification of several regulatory regions of the viral genome. However, the viral and host factors determining the disease manifestations and clinical outcomes for EBV infections are as yet undefined. Additionally, both B-cells and epithelial cells appear to be sites of viral latency and replication. While a number of investigators are studying specific aspects of EBV replication and tumorigenesis, delineation of viral and host factors which may determine the outcome of individual EBV infections has been difficult to approach directly. The present RFA is for a single competition with a deadline of August 3, 1989 for receipt of applications, and June 3, 1989 for receipt of letters of intent. II. BACKGROUND On April 25-26, 1988, the Biological Carcinogenesis Branch, Division of Cancer Etiology, NCI and the Bacteriology and Microbiology Branch, Microbiology and Infectious Disease Program, NIAID co-sponsored a workshop, entitled "Mechanisms of Pathogenic Diversity of Epstein-Barr Virus." The goals of the workshop were to assess the state of our knowledge of the mechanisms of pathogenic diversity of Epstein-Barr virus (EBV) and to determine whether there were particular research areas that needed additional emphasis or support. The workshop participants identified a number of issues in EBV oncogenesis in which our knowledge is limited and there is a need for more active investigation. For example, EBV has been associated with both lymphoid and epithelial neoplasias, which presumably are initiated from a reservoir(s) of EBV latently infected cells. It is not clear whether there is a continuous infection and immortalization/transformation of B-cells from an epithelial reservoir, or whether separate or single reservoirs of EBV exist in EBV infected individuals. The viral and host factors which normally prevent the progression from latent infection to oncogenesis and the viral gene products which are involved in the neoplastic conversion have not been defined. Experiments to approach these issues are technically difficult and are limited by a number of factors including: the lack of a lytic replication system, the lack of virus mutants, the lack of animal models, limited quantities of human tissues, limited availability of gene product specific reagents such as monoclonal antibodies, and limitation of methodologies currently available to detect viral gene products present in low quantities or in a small percent of cells. Thus, new approaches to address these fundamental issues of EBV oncogenesis are needed. III. RESEARCH GOALS AND SCOPE The overall thrust of this RFA is to stimulate research on the mechanism(s) of EBV oncogenesis by developing and using new methodological approaches to overcome the difficulties inherent in EBV research. Examples of research objectives (which are not all inclusive) would include the following: (i) use of novel methods and probes to define RNA transcripts unique to or with clinical significance for different EBV neoplasias, (ii) use of new approaches to alter (mutate) the viral genome followed by the study of the effect of altered genes on viral oncogenesis, (iii) use of cell lines expressing individual EBV gene products (both structural and regulatory) to define viral genes and assess their role in the neoplastic process, (iv) use of specific reagents such as monoclonal antibodies to viral gene products to determine the role of regulatory and structural EBV proteins in the neoplastic process, (v) measurement of host response to individual viral proteins with the goal of delineating differences in the host response in specific EBV-associated neoplasias, (vi) delineation of differences in cell-mediated responses in individuals with different EBV neoplasias, and (vii) exploitation of EBV's unique pathologic aspects, such as the use of the CR-2 receptor and the activation of B-cells during the infectious process, to develop approaches to alter these unique aspects of EBV pathogenesis with the ultimate aim of preventing or reversing neoplastic conversion. Where appropriate, collaborative arrangements to facilitate the achievement of research goals should be considered. Applications should contain as goals both methodological development and application to a specific area of EBV oncogenesis; basic and/or clinical issues are considered as appropriate subjects for this RFA. Furthermore, in studies involving differences between various EBV-associated neoplasias, investigators should consider not only the classical EBV-associated neoplasias, such as Burkitt's lymphoma and nasopharyngeal carcinoma, but also give some emphasis to newer EBV-related neoplasias such as EBV lymphomas in immunocompromised individuals, EBV tumors in other areas of the oropharynx such as the parotid gland, and other new EBV-associated diseases such as hairy leukoplakia. IV. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) grant-in-aid. Responsibility for the planning, direction and execution of the proposed project will be solely that of the applicant. Except as stated in this RFA, awards will be administered under PHS grants policy as stated in the Public Health Service Grants Policy Statement, DHHS Publication No. (OASH) 82-50,000, revised January 1, 1987. This RFA is a one time solicitation. Generally future unsolicited competing renewal applications will compete as research project applications with all other investigator initiated applications and be reviewed in a standing Division of Research Grants study section. However, should the NCI determine that there is a sufficient continuing program need, NCI may announce a request for renewal applications. Approximately $ 850,000 in total costs per year for five (5) years will be committed to specifically fund applications which are submitted in response to this RFA. It is anticipated that four (4) to five (5) awards will be made. This funding level is dependent on the receipt of a sufficient number of applications of high scientific merit. The total project period for applications submitted in response to the present RFA should not exceed five (5) years. The earliest feasible start date for the initial awards will be April 1, 1989. Although this program is provided for in the financial plans of the National Cancer Institute (NCI), award of grants pursuant to this RFA is also contingent upon the availability of funds for this purpose. Non-profit and for-profit institutions are eligible to apply. Foreign as well as domestic institutions are eligible. V. REVIEW PROCEDURES AND CRITERIA REVIEW PROCEDURE Upon receipt, applications will be reviewed initially by the Division of Research Grants for completeness. Incomplete applications will be returned to the applicant without further consideration. Evaluation for responsiveness to the RFA is an NCI program staff function. Applications will be judged to determine how well they meet the goals and objectives of the program as described in the RFA. Applications which are judged non-responsive will be administratively inactivated, but may be submitted as investigator initiated grants at the next receipt date. Questions concerning the relevance of proposed research to the RFA should be directed to program staff as described in Section VII. In cases where the expected number of applications is large compared to the number of awards to be made, the NIH will conduct an administrative prereview (triage) to eliminate those which are clearly not competitive. The NIH will withdraw from further competition those applications judged to be noncompetitive and notify the applicant and institutional business official. Those applications judged to be both responsive and competitive will be evaluated, in accordance with the criteria stated below for scientific/technical merit by an appropriate peer review group convened by the Division of Extramural Activities, NCI. The second level of review by the National Cancer Advisory Board considers the special needs of the Institute and the priorities of the National Cancer Program. REVIEW CRITERIA Proposals responsive to this competitive solicitation will be reviewed in accordance with the criteria stated below. 1 Relevance of the proposed research to the aims of the RFA, i.e., potential for providing insight on the mechanism(s) of oncogenesis by Epstein-Barr virus. 2 The scientific merit of the proposed approach, including the adequacy and quality of the methodological approach and the research design. Familiarity with the proposed techniques should be demonstrated, e.g., by the presentation of preliminary data. 3 The expertise and qualifications of the principal investigator and proposed staff and/or collaborators to perform the proposed experiments. 4 Documentation of the adequacy of the facilities and resources. The review group will recommend an appropriate budget for each approved application. VI. METHOD OF APPLYING The regular research grant application, form PHS-398 (revised 9/86) must be used in applying for these grants. These forms are available at most institutional business offices; from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Room 449, Westwood Building, 5333 Westbard Avenue, Bethesda, Maryland 20892; or from the NCI Program Director named below. The RFA label available in the 9/86 revision of Application Form 398 must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of your application such that it may not reach the review committee in time for review. In addition, the title of the application and the RFA number should be typed on line 2 of the face page of the application form. Submit a signed, typewritten original of the application, including the Checklist, and four (4) signed, exact photocopies, in one package to the Division of Research Grants at the address below. The photocopies must be clear and single sided. DIVISION OF RESEARCH GRANTS National Institutes of Health Westwood Building, Room 240 Bethesda, Maryland 20892** At the time of submission, two (2) additional copies of the application should also be sent to: REFERRAL OFFICER Division of Extramural Activities National Cancer Institute Room 848, Westwood Building 5333 Westbard Avenue Bethesda, Maryland 20892 Applications should be received by August 3, 1989. If an application is received after that date, it will not be accepted. Also the Division of Research Grants will not accept any application in response to this announcement that is the same as one currently being considered by an NIH awarding unit. Animal and human subject approval clearances should be submitted with the applications to expedite the review process. LETTER OF INTENT Prospective applicants are asked to submit, by June 3, 1989, a letter of intent that includes a descriptive title of the proposed research, the name and address of the principal investigator, the names of other key personnel, the participating institutions, and the number and title of the RFA in response to which the application is being submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information which it contains is extremely helpful in planning for the review of applications. First, it allows NCI staff to estimate the potential review workload and to avoid possible conflict of interest in the review. In addition, should it appear that the potential applicant has misunderstood the objects of the RFA or opted for an inappropriate funding mechanism, NCI staff will respond to such letters. Therefore, NCI would like to emphasize the benefits to the applicant and to staff of having a principal investigator submit a letter of intent. The letter establishes communication between the potential applicant and program staff initiating the RFA. Program staff may be able to assist prospective applicants in several areas including scientific content and objectives of an application, size and focus of a research program, organization of an application, and appropriate use of consultants. The letter of intent should be sent to: Dr. Susan B. Spring Program Director DNA Virus Studies I Biological Carcinogenesis Branch Division of Cancer Etiology National Cancer Institute Executive Plaza North, Room 540 Bethesda, Maryland 20892 Telephone: (301) 496-4533 VII. INQUIRIES Written or telephone inquiries concerning the objectives and scope of this RFA or inquiries about whether or not specific proposed research would be responsive are encouraged and should be directed to Dr. Susan B. Spring at the above address. The program director welcomes the opportunity to clarify any issues or questions from potential applicants. ------------------------ This program is described in the Catalog of Federal Domestic Assistance No. 13.393, Cancer Cause and Prevention Research. Awards are under authorization of the Public Health Service Act, Section 301 (c), Public Law 78-410, as amended; 42 U.S.C. 241; the Small Business Innovation Development Act, Public Law 97-219, and Section 410 as amended by Public Law 99-158, 42 U.S.C. 285; and administered under PHS grant 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. DEVELOPMENT OF SOMATIC CELL GENE THERAPY APPROACHES FOR SPECIFIC INBORN METABOLIC DISEASES RFA AVAILABLE: 89-DK-04 P.T. 34; K.W. 0715135, 1002058, 0780015, 0755020 National Institute of Diabetes and Digestive and Kidney Application Receipt Date: July 17, 1989 Introduction and Background: The Metabolic Diseases and the Cystic Fibrosis Research Programs, Division of Diabetes, Endocrinology and Metabolic Diseases, support basic and clinical research and research training related to the etiology, diagnosis, prevention and treatment of inborn metabolic diseases such as: cystic fibrosis (CF), other diseases of transport, aminoacidemias, organic acidurias, lysosomal storage diseases, diseases of purine and pyrimidine metabolism, glycogen storage diseases, diseases of copper metabolism, hereditary amyloidosis, etc. This initiative is an important component of a broad program for the development or improvement of therapies for orphan diseases. This initiative is intended to encourage qualified scientists to submit regular research project grant (R01) or program project grant (P01) applications which propose novel studies to facilitate development of approaches to somatic cell gene therapy. For the purposes of this program gene therapy is defined as a molecular genetic therapeutic approach that utilizes somatic cell gene transfer to correct or ameliorate the inborn error. A recent meeting on "Gene Therapy: It's Potential Application to Cystic Fibrosis," called for development of techniques for somatic cell gene therapy in cystic fibrosis. Therefore, proposals related to CF or other inborn metabolic diseases could focus on any of the applicable research areas described in this announcement. Objectives and Scope: This program is intended to encourage submission of proposals to develop approaches to human gene therapy for inborn metabolic diseases. Areas of research include but are not limited to the following: o development of more efficient and more rapid approaches to chromosomal localization of relevant genes o identification and characterization of retroviral and other vectors suitable for gene transfection o development of efficient gene transfection techniques o development of techniques for homologous recombination of transfected gene/s and the host chromosome in model cells, or mice or other animal models o development of cell lines and/or mouse models suitable for gene therapy studies o development of techniques for isolation and maintenance of host cells suitable for gene therapy o introduction of the transfected cell into the relevant target organs of an animal model and the study of in vivo expression of the functional protein This program is intended to stimulate basic research and development of techniques focused on achieving successful human gene therapy. In this regard, studies on the general mechanisms of recombination and transfection are not suitable. It is recommended that the system selected by the applicant for study be relevant to the disease categories described under the "Introduction and Background" Section. 1. The program encourages studies of cell types already successfully used in gene transfection, e.g. the pluripotent hematopoietic stem cell, hepatocytes, fibroblasts, or of other cells, such as epithelial cells, which are potential targets for gene therapy. Therefore, finding markers and other assay systems to identify cell types suitable for transfection as well as developing cell lines with appropriate characteristics for transfection are important goals of this program. 2. Retroviral vectors are widely used in studies of mammalian gene transfer and expression. Further studies on developing new, more effective, transcriptionally disabled retroviral or viral vectors, viral vectors with tropism for particular cell types, or improvement of presently available vectors, are encouraged. In addition, studies of design and development of new types of transfection vectors are relevant to this announcement. 3. New mouse models of disease could be particularly useful for evaluation of therapeutic efficacy and possible toxicity of somatic gene transfer and ultimately gene therapy. The novel techniques of germ line transfection allow the development of transgenic mice as models of disease. This program encourages development of such models and of transgenic cell and mouse models by homologous or site specific recombination. 4. Studies of the in vivo expression and regulation of transfected genes are of great interest. A major objective of this research area is the achievement of homologous recombination with in vivo expression of the transfected gene at therapeutic levels. Studies on regulatory elements such as tissue specific enhancers which would affect in vivo expression of the exogenous gene following transplantation could help in achieving successful gene therapy. Also, defining growth factors which regulate cell division and viability in vivo could be important. The above examples are by no means intended to restrict the range of research. Prospective applicants are encouraged to consider other topics of relevance to achieving successful gene therapy in inherited metabolic diseases. Mechanism of Support The mechanism of support for this program will be the grant-in-aid (R01) and the program project grant (P01). Although this solicitation is included in the funding plans for Fiscal Year 1990 for NIDDK, support is contingent upon actual availability of appropriated funds. The NIDDK plans to designate a total of $2.0 million (direct and indirect costs) for the support of applications submitted in response to this solicitation; however, the amounts to be awarded will depend upon the overall merit, budget, and scope of the applications received. It is anticipated that approximately 5 to 10 grants will be awarded under this solicitation. APPLICATION AND REVIEW PROCEDURES Applications must be submitted on Form PHS 398 (revised 9/86), available at most institutional business offices or from the Division of Research Grants, NIH. To identify the application as a response to this RFA, please check "Yes" on item two of page one of the application and enter "NIDDK-RFA-89-DK-04 on "Somatic Cell Gene Therapy Approaches". The RFA label (found in the 9/86 revision of application form PHS 398) must be affixed to the bottom of the face page of the orginal copy of the application. Failure to use this label could result in delayed processing of your application such that it will not reach the review committee in time. If an application submitted in reponse to this RFA is identical to a research grant application already submitted to the NIH for review, the applicant will be asked to withdraw the pending application before the new one is accepted. Simultaneous submission of identical applications will not be allowed. Both a P01 application and the projects which are components of this P01 may not be submitted simultaneously in response to this RFA. Applications received in response to this solicitation will be reviewed in accord with the usual NIH peer review procedures. Applications will first be reviewed for scientific and technical merit by a Special Initial Review Group, convened solely to review these applications by the Review Branch, Division of Extramural Activities, NIDDK. This group will be composed primarily of non- federal scientific consultants. It is expected that site visits will not be conducted and therefore the submitted applications should be complete and stand alone for purposes of review. The applications will then be reviewed by the National Diabetes and Digestive and Kidney Diseases Advisory Council of NIDDK. Application Receipt A single reply date of July 15, 1989, will be strictly enforced. Applications received after that day will be returned. An anticipated schedule for review and award is detailed below: APPLICATION INITIAL COUNCIL EARLIEST RECEIPT REVIEW REVIEW START DATE July 15, 1989 Oct/Nov 1989 Feb. 1990 April 1990 The original and four copies of the application should be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building - Room 240 Bethesda, Maryland 20892** Two additional copies of the application are to be sent to: Review Branch National Institute of Diabetes and Digestive and Kidney Diseases, NIH Westwood Building, Room 406 Bethesda, MD 20892 CONSULTATION WITH PROGRAM STAFF Prospective applicants are encouraged to discuss their ideas with Program staff (see below) to determine whether they fit guidelines of this RFA. Applications which, in the opinion of staff, do not meet the stated objectives, wil be returned without review. Applicants who intend to submit P01 applications should request a copy of NIDDK's guidelines for program project grants. Robert Katz, Ph.D. Nancy Lamontagne, Ph.D. Director, Metabolic Diseases Reseach Director, Cystic Fibrosis Research Program, NIDDK Program, NIDDK Westwood Bldg., Room 607A Westwood Bldg., Room 607 Bethesda, Maryland 20892 Bethesda, Maryland 20892 Telephone: (301) 496-7997 Telephone: (301) 496-4980 This program is described in the Catalog of Federal Domestic Assistance, No.13.847, Diabetes, Endocrinology, and Metabolic Diseases. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301, (Public Law 78-410), as amended; 42 USC 241) and administered under PHS grant policies and Federal Regulations, most specifically at 42 CFR Part 52 and CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. **THE MAILING ADDRESS GIVEN FOR SENDING APPLICATIONS TO THE DIVISION OF RESEARCH GRANTS OR CONTACTING PROGRAM STAFF IN THE WESTWOOD BUILDING IS THE CENTRAL MAILING ADDRESS FOR THE NATIONAL INSTITUTES OF HEALTH. APPLICANTS WHO USE EXPRESS MAIL OR A COURIER SERVICE ARE ADVISED TO FOLLOW THE CARRIER'S REQUIREMENTS FOR SHOWING A STREET ADDRESS. THE ADDRESS FOR THE WESTWOOD BUILDING IS: 5333 Westbard Avenue Bethesda, Maryland 20816