From owner-sci-resources@net.bio.net Sun Aug 04 23:00:00 1996 Path: biosci!biosci!not-for-mail From: Mary Hilts Newsgroups: bionet.sci-resources Subject: DoD Fast Track Date: 5 Aug 1996 15:25:13 -0700 Organization: Foresight Science & Technology Lines: 79 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <32023EBB.1D0F@foresnt.com> NNTP-Posting-Host: net.bio.net We (Foresight Science & Technology) are under contract with the DoD to assist them in finding candidates for their SBIR "Fast Track" program. Through this program funds are available for research and technology areas that fall within the DoD's mission. This task is awkward in this particular forum (newsgroups) in that it is not research exchange, yet it is not advertisement either. What I believe it could be categorized as is information exchange; "The DoD has R&D money available, your readers may be eligible, we are informing them of the availability of this funding". If you have any questions, please e-mail me, I appreciate your communication. Otherwise, please post the following. Mary Hilts, Internet support maryh@foresnt.com Foresight Science & Technology *************************************************** ************************ Defense Department offering up to 4X match on private sector investments in small high-technology companies. *************************************************** ************************ DoD's Small Business Innovation Research (SBIR) program will fund $450 million in early-stage R&D projects at small high-technology companies in 1996, in technology areas that fall within the broad DoD mission. Effective immediately, DoD will give its highest priority in making SBIR awards to small companies that are able to attract independent third-party investors -- such as venture capital firms, large companies, or "angel" investors. If selected for award, these small companies will receive uninterrupted DoD funding of up to $850,000 over a two-and-a-half year period. In practice, this means that an investor that offers to help fund an early-stage technology project at a small company can obtain a match of between $1 and $4 in DoD SBIR funds for every $1 the investor puts in. This new policy -- the SBIR "Fast Track" -- was approved for implementation by Under Secretary of Defense (Acquisition & Technology) Dr. Paul Kaminski in June, 1995. Its purpose is to significantly increase DoD's success in converting SBIR research into affordable, high-performance products which serve military and commercial customers. For more information: * call David Speser at (407) 791-0720 or e-mail david@foresnt.com * see the page entitled "DoD SBIR Fast Track" on the World Wide Web at http://www.seeport.com/SBIR/fasttrk.htm * contact our DoD Fast Track listserver by e-mailing list@seeport.com with the message "join DoD" on the first line of your e-mail. *************************************************** ****************** From owner-sci-resources@net.bio.net Sun Aug 04 23:00:00 1996 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS, 3 August 1996 Date: 5 Aug 1996 16:15:14 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 96 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <4u5va2$gi8@net.bio.net> NNTP-Posting-Host: net.bio.net This message contains a summary of the documents added to the NSF STIS system for the week ending August 3, 1996. Reference material concerning STIS follows the summary. ------------------------------------------------------------------------ ** NEW DOCUMENTS ON STIS ** Document Type: Program Guideline Title: NSF 94-100 - University-Industry Cooperative Research Programs in the Mathematical Sciences File size (bytes): 36441 STIS Filename: nsf94100.txt Title: NSF 96-119 CISE Postdoctoral Research Associates in Computational Science and Engineering & Experimental Computer Science File size (bytes): 14404 STIS Filename: nsf96119.txt Document Type: Report Title: NSF 96-30 Graduate Education and Postdoctoral Training in the Mathematical and Physical Sciences File size (bytes): 20449 STIS Filename: nsf9630.txt ------------------------------------------------------------------------ ** UPDATES TO EXISTING STIS DOCUMENTS ** Document Type: Phone Book Title: NSF Alpha Telephone Directory File size (bytes): 113743 STIS Filename: phnalpha.txt Also available: phnalpha.dlm Title: NSF Organization Telephone Directory File size (bytes): 123609 STIS Filename: phnorg.txt Document Type: Program Guideline Title: NSF 94-100 - University-Industry Cooperative Research Programs in the Mathematical Sciences File size (bytes): 36441 STIS Filename: nsf94100.txt Title: NSF 95-111 Grant Opportunities for Academic Liaison with Industry(GOALI) File size (bytes): 23416 STIS Filename: nsf95111.txt Title: NSF 95-112 Grant Opportunities for Academic Liaison with Industry File size (bytes): 16989 STIS Filename: nsf95112.txt ------------------------------------------------------------------------ ** FOR YOUR REFERENCE ** ------------------------------------------------------------------------ HOW TO OBTAIN DOCUMENTS The above files can be retrieved in electronic form using the STIS system. If you don't know how to use STIS, send an E-mail message to stisinfo@nsf.gov (Internet). You will receive a copy of the STIS flyer via E-mail. If you are already using STIS, you can use the information above to retrieve these files: Documents via E-mail: Send a message to stisserve@nsf.gov (Internet). Use the "STIS Filename" shown above in the "get" command. For example, to retrieve nsf95112.txt, the text of your message should be as follows: get nsf95112.txt Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve nsf95112.txt, you would enter: ftp> get nsf95112.txt WAIS or Gopher: Do a word search on the filename as shown in the summary. If you want a *printed* copy of a document: Send your name and postal mailing address, and the document title and number to "pubs@nsf.gov" (Internet). If you have problems with the above procedures: Send a message to "stis@nsf.gov" (Internet). From owner-sci-resources@net.bio.net Tue Aug 06 23:00:00 1996 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 25, no. 26, pt. 1of1, 2 August 1996 Date: 7 Aug 1996 16:33:41 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 369 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <4ub94l$h78@net.bio.net> NNTP-Posting-Host: net.bio.net NIH GUIDE - Vol. 25, No. 26 - August 2, 1996 $$INDEX BEGIN ******************************************************* NOTICES $$INDEX N1 ********************************************************** JAPAN SOCIETY FOR THE PROMOTION OF SCIENCE FELLOWSHIPS Fogarty International Center INDEX: FOGARTY INTERNATIONAL CENTER $$INDEX N2 ********************************************************** INTERNATIONAL GRANTS FOR U.S. AND FORMER SOVIET UNION SCIENTISTS Fogarty International Center INDEX: FOGARTY INTERNATIONAL CENTER NOTICES OF AVAILABILITY (RFPs/RFAs/PAs) $$INDEX R1 12/18/96 ************************************************* STRUCTURAL BIOLOGY OF AIDS RELATED PROTEINS (RFA GM-96-012) National Institute of General Medical Sciences INDEX: GENERAL MEDICAL SCIENCES $$INDEX R2 03/12/97 ************************************************* MITOCHONDRIAL DNA MUTATIONS IN HEART, LUNG AND BLOOD DISEASES (RFA HL-96-013) National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD $$INDEX P1 ********************************************************** INNOVATIVE DRUG DISCOVERY RESEARCH IN AIDS OPPORTUNISTIC INFECTIONS (PA-96-068) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES THE NIH GUIDE IS AVAILABLE ELECTRONICALLY VIA BITNET OR INTERNET, BY SUBSCRIPTION, AND IS ALSO ON THE NIH GOPHER (GOPHER.NIH.GOV) AND THE NIH WEBSITE (HTTP://WWW.NIH.GOV). ALTERNATIVE ACCESS IS THROUGH THE NIH GRANT LINE VIA MODEM (DATA LINE 301/402-2221); CONTACT DR. JOHN JAMES AT 301/435-2801 FOR DETAILS ON THE NIH GRANT LINE. THE PHS STRONGLY ENCOURAGES ALL GRANT AND CONTRACT RECIPIENTS TO PROVIDE A SMOKE-FREE WORKPLACE AND PROMOTE THE NON-USE OF ALL TOBACCO PRODUCTS. IN ADDITION, PUBLIC LAW 103-227, THE PRO-CHILDREN ACT OF 1994, PROHIBITS SMOKING IN CERTAIN FACILITIES (OR IN SOME CASES, ANY PORTION OF A FACILITY) IN WHICH REGULAR OR ROUTINE EDUCATION, LIBRARY, DAY CARE, HEALTH CARE OR EARLY CHILDHOOD DEVELOPMENT SERVICES ARE PROVIDED TO CHILDREN. THIS IS CONSISTENT WITH THE PHS MISSION TO PROTECT AND ADVANCE THE PHYSICAL AND MENTAL HEALTH OF THE AMERICAN PEOPLE. ALL COMPETING GRANT APPLICATIONS SUBMITTED TO THE NATIONAL INSTITUTES OF HEALTH MUST BE SENT TO: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) THE GRANTS INFORMATION OFFICE, DRG, HAS BEEN INCORPORATED INTO THE NEW OFFICE OF EXTRAMURAL OUTREACH & INFORMATION RESOURCES, OFFICE OF EXTRAMURAL RESEARCH, OFFICE OF THE DIRECTOR, NIH. REQUESTS FOR APPLICATION FORMS, PUBLICATIONS, AND OTHER INFORMATION MAY BE DIRECTED TO THE FOLLOWING: OFFICE OF EXTRAMURAL OUTREACH & INFORMATION RESOURCES NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, MSC 7910 BETHESDA, MD 20892-7910 TELEPHONE: (301) 435-0714 EMAIL: ASKNIH@ODROCKM1.OD.NIH.GOV $$INDEX END ********************************************************* NOTICES $$N1 BEGIN ********************************************************** JAPAN SOCIETY FOR THE PROMOTION OF SCIENCE FELLOWSHIPS NIH GUIDE, Volume 25, Number 26, August 2, 1996 P.T. 22; K.W. 0710030, 0404000 Fogarty International Center Through arrangements made with the Fogarty International Center, the Japan Society for the Promotion of Science (JSPS) will award up to 30 short-term fellowships for U.S. researchers in the biomedical and behavioral sciences to pursue collaborative research visits to Japan for periods ranging from seven to sixty days. Applicants must be U.S. citizens or permanent residents and hold a doctoral degree or equivalent in the biomedical or behavioral sciences. Ph.D. and M.D. candidates who can demonstrate that their collaboration with Japanese colleagues holds exceptional professional promise also may apply. The deadline for receipt of applications is October 1. INQUIRIES Inquiries regarding this program may be directed to: Mr. Michael Snyder Program Officer for Japan Fogarty International Center Building 31, Room B2C11 31 Center Drive, MSC 2220 Bethesda, MD 20892-2220 Telephone: (301) 496-4784 FAX: (301) 480-3414 Email: snyderm@nih.gov $$N1 END ************************************************************ $$N2 BEGIN ********************************************************** INTERNATIONAL GRANTS FOR U.S. AND FORMER SOVIET UNION SCIENTISTS NIH GUIDE, Volume 25, Number 26, August 2, 1996 P.T. 34; K.W. 0710030 Fogarty International Center Through a program made possible by an award from the NIH, the U.S. Civilian Research and Development Foundation (CRDF) for the Newly Independent States of the Former Soviet Union (FSU) has announced a new competition for grants to support research projects between U.S. scientists and their counterparts in the FSU. Current NIH grantees and intramural scientists are invited to apply jointly with their counterparts in the FSU. Two-year cooperative grants of up to $80,000 will be awarded. All proposals will be evaluated through competitive peer review. The deadline for receipt of applications is February 15, 1997. INQUIRIES A detailed program announcement and application instructions are available from the U.S. Civilian Research and Development Foundation (CRDF) at http://www.crdf.inter.net; Email: information@crdf.org; telephone: (703) 526-9720; FAX: (703) 526-9721; and from: Ms. Karen Peterson Program Officer for Russia and the NIS Fogarty International Center Building 31, Room B2C11 31 Center Drive, MSC 2220 Bethesda, MD 20892-2220 Telephone: (301) 496-4784 FAX: (301) 480-3414 Email: p9k@cu.nih.gov $$N2 END ************************************************************ NOTICES OF AVAILABILITY (RFPs/RFAs/PAs) $$R1 BEGIN GM-96-012 FULL-TEXT ************************************** STRUCTURAL BIOLOGY OF AIDS RELATED PROTEINS NIH GUIDE, Volume 25, Number 26, August 2, 1996 RFA AVAILABLE: GM-96-012 P.T. 34; K.W. 0715008, 0755025, 0760070 National Institute of General Medical Sciences Letter of Intent Receipt Date: November 18, 1996 Application Receipt Date: December 18, 1996 PURPOSE The National Institute of General Medical Sciences (NIGMS) reannounces its interest in receiving applications to apply modern methods of molecular structure determination and analysis in developing new approaches to structure-based drug design. The intent is to develop new approaches to the treatment of AIDS and associated opportunistic infections. The mechanism of support will be the program project grant (P01). The estimated funds (total costs) available for the first year of support for the entire program is $8,000,000. It is anticipated that six to ten new and competing applications will be funded. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), Structural Biology of AIDS-Related Proteins, is related to the priority area of HIV infection. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800). INQUIRIES The RFA, which describes the research objectives, application procedures, review considerations, and award criteria for this solicitation, may be obtained electronically through the NIH Grant Line (data line 301/402-2221), the NIH GOPHER (gopher.nih.gov), and the NIH Website (http://www.nih.gov), and by mail and email from the program contact listed below. James C. Cassatt, Ph.D. Division of Cell Biology National Institute of General Medical Sciences 45 Center Drive, Room 2AS-19C - MSC 6200 Bethesda, MD 20892 Telephone: (301) 594-0828 FAX: (301) 480-2004 Email: czj@cu.nih.gov $$R1 END ************************************************************ $$R2 BEGIN HL-96-013 FULL-TEXT ************************************** MITOCHONDRIAL DNA MUTATIONS IN HEART, LUNG AND BLOOD DISEASES NIH GUIDE, Volume 25, Number 26, August 2, 1996 RFA AVAILABLE: HL-96-013 P.T. 34; K.W. 0760053, 0715040, 0715032, 0715165 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: January 24, 1997 Application Receipt Date: March 12, 1997 PURPOSE This initiative will foster research on molecular, cellular, genetic, and epidemiologic approaches to elucidate the role of mitochondrial DNA (mtDNA) mutations in heart, blood vessels, blood and lung diseases. Its goals are to define mechanisms by which mtDNA mutations cause tissue-specific, progressive diseases, and to elucidate the cause and effect relationships between alterations in this genome and pathological phenotypes. The ultimate purpose of this initiative is the development of effective strategies for prevention and treatment of cardiovascular, pulmonary, and hematologic disorders due to mitochondrial DNA mutations in humans. Although this Request for Applications (RFA) is sponsored by the National Heart, Lung, and Blood Institute (NHLBI), other Institutes and Centers of the NIH may also have an interest in mitochondrial research. Applications will be assigned to the most appropriate Institute/Center on the basis of established PHS referral guidelines. It is anticipated that for FY 1997, approximately $1,800,000 total costs will be available to support approximately six new research project grants (R01) under this Request for Applications (RFA). HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Mitochondrial DNA Mutations in Heart, Blood and Lung Diseases, is related to the priority areas of heart disease and stroke, diabetes and chronic disabling conditions, and environmental health. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800). INQUIRIES The RFA, which describes the research objectives, application procedures, review considerations, and award criteria for this solicitation, may be obtained electronically through the NIH Grant Line (data line 301/402-2221), the NIH GOPHER (gopher.nih.gov), and the NIH Website (http://www.nih.gov), and by mail and email from the program contact listed below. Dr. Isabella Liang Division of Heart and Vascular Diseases National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Suite 9142, MSC 7940 Bethesda, MD 20892-7940 Telephone: (301) 435-0520 FAX: (301) 480-1335 Email: liangi@gwgate.nhlbi.nih.gov $$R2 END ************************************************************ $$P1 BEGIN PA-96-068 FULL-TEXT ************************************** INNOVATIVE DRUG DISCOVERY RESEARCH IN AIDS OPPORTUNISTIC INFECTIONS NIH GUIDE, Volume 25, Number 26, August 2, 1996 PA AVAILABLE: PA-96-068 P.T. 34; K.W. 0715008, 0755025, 0765035, 0715125 National Institute of Allergy and Infectious Diseases PURPOSE The National Institute of Allergy and Infectious Diseases gives special consideration for funding to scientifically meritorious and appropriate applications in response to Program Announcements. Program Announcements identify areas of ongoing research emphasis for the NIAID. The Opportunistic Infections Research Branch (OIRB) of the Therapeutics Research Program in the Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), invites applications for Innovative Drug Discovery Research in AIDS Opportunistic Infections. The purpose of this PA is to encourage investigator-initiated grant applications that involve creative and original research that emphasizes under-exploited facets of the basic biology, biochemistry, and pathophysiology of the opportunistic pathogens necessary to propel advances in improved therapies. The PA encourages applications for studies on the following AIDS-associated pathogens: human cytomegalovirus, JC virus, Mycobacterium avium, Pneumocystis carinii, Cryptosporidium parvum, the Microsporida, and Cryptococcus neoformans. Funding mechanisms to be used are research project grants (R01), First Independent Research Support and Transition (FIRST) (R29) awards, and Interactive Research Project Grants (IRPG). Applications in this area are also accepted for the SBIR and STTR programs. Research in the following areas will be considered responsive to this PA: discovery of efficacious new antibiotics; cellular and molecular biology of the pathogens leading to identification of new chemo- or immuno-therapeutic targets; pathogen physiology, biochemistry and metabolism relating to drug susceptibility and resistance; development of improved culture and animal model systems; identification of new drugs from natural products and synthetic chemical compounds; rapid, noninvasive diagnostic methods; and development of improved drug delivery systems. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This PA, Innovative Drug Discovery Research in AIDS Opportunistic Infections, is related to the priority area of HIV infection. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-0325 (telephone 202/512-1800). INQUIRIES The PA, which describes the research objectives, application procedures, review considerations, and award criteria for this solicitation, may be obtained electronically through the NIH Grant Line (data line 301/402-2221), the NIH GOPHER (gopher.nih.gov), and the NIH Website (http://www.nih.gov), and by mail and email from the program contact listed below. Chris Lambros, Ph.D. Division of AIDS National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 2C40, MSC 7620 Bethesda, MD 20892-7620 Telephone: (301) 402-2304 FAX: (301) 402-3171 Email: chris_lambros@nih.gov $$P1 END ************************************************************ From owner-sci-resources@net.bio.net Tue Aug 06 23:00:00 1996 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA GM-96-012 - V25(26) 08/02/96 Date: 7 Aug 1996 16:34:04 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 333 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <4ub95c$h7v@net.bio.net> NNTP-Posting-Host: net.bio.net STRUCTURAL BIOLOGY OF AIDS RELATED PROTEINS NIH Guide, Volume 25, Number 26, August 2, 1996 RFA: GM-96-012 P.T. 34; K.W. 0715008, 0755025, 0760070 National Institute of General Medical Sciences Letter of Intent Receipt Date: November 18, 1996 Application Receipt Date: December 18, 1996 PURPOSE The National Institute of General Medical Sciences (NIGMS) reannounces its interest in receiving applications to apply modern methods of molecular structure determination and analysis in developing new approaches to structure-based drug design. The intent is to develop new approaches to the treatment of AIDS and associated opportunistic infections. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), Structural Biology of AIDS Related Proteins, is related to the priority area of HIV infection. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Foreign organizations are not eligible to apply. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORT The mechanism of support will be the program project grant (P01). The circumstances under which NIGMS will support this RFA are the same as those described in the notice, "Support of Program Project Grants," published in the NIH Guide, Vol. 25, No. 10, March 29, 1996. It is expected that three or more investigators, all pursuing independent, interrelated projects, will be involved. One scientist must be designated by the applicant institution as the Principal Investigator and must bear the responsibility for the scientific and fiscal management of the program project grant. Most of the collaborating scientists should be independent investigators in accordance with the NIGMS program project notice cited above. Equipment and other core resources necessary for the accomplishment of the objectives of the program project grant may be requested. This RFA is 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. FUNDS AVAILABLE This RFA is a one-time solicitation, and represents a request for competing renewal applications funded under RFA GM-91-02 (STRUCTURAL BIOLOGY AS APPLIED TO THE PROBLEM OF TARGETED DRUG DESIGN, WITH POTENTIAL APPLICABILITY TO THE TREATMENT OF AIDS), and an opportunity for new groups to apply. The estimated funds (total costs) available for the first year of support for the entire program is $8,000,000. It is anticipated that six to ten applications will be funded. The level of support 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 this RFA may not exceed five years. The anticipated award date will be July 1, 1997. Although this program is provided for in the financial plans of NIGMS, the award of grants pursuant to this RFA is contingent on the availability of funds for this purpose. RESEARCH OBJECTIVES Background In 1987 the NIGMS initiated a program to support groups interested in developing the area of structure-based drug design with a specific emphasis on AIDS related systems. Since that time, considerable progress has been made through this program as well as elsewhere at NIH and in industry. The structures of several HIV proteins have been determined. These structures include the HIV, SIV and FIV proteases, the HIV reverse transcriptase, the zinc finger domains of the HIV nucleocapsid protein, and the catalytic domain of integrase. The first generation of HIV protease inhibitors have either been approved or are awaiting approval by the FDA. Other Although this progress has been significant, many areas require further investigation. For example, some targets, such as the membrane-bound gp120/gp41 complex, have not yielded to detailed structural determination. As another example, the development of drug resistance and complications raised by opportunistic infections present new challenges. Finally, despite the major advances that have been made in the speed with which structures can be determined and in our understanding of the theoretical basis of ligand binding to proteins, the limiting step in the process of drug design remains the lack of generalizable, efficient and reproducible approaches to the use of macromolecular structures to design lead compounds. Consequently, we are encouraging applications from research groups with an interest in developing the concepts and methodologies of structure-based drug design. Because of the progress that has been made in the determination of the structures of either AIDS-related proteins or proteins key to the survival of organisms that commonly cause opportunistic infections in people infected with HIV, it is expected that these will serve as a test bed for any new methodologies developed. Other possible targets that can be considered are biological macromolecules from the host that are involved in the uptake, transport, and integration of the viral genome. Furthermore, since drug resistance is now well-established as a major problem, the ability of potential inhibitors to withstand the effects of mutations of the target should be included in design principles. The central disciplines covered by this RFA are x-ray crystallography, NMR and molecular modeling augmented by expertise in organic synthesis, molecular enzymology, and virology. Groups with well-established expertise in this broad area but which have not previously been involved in AIDS research are encouraged to apply. SPECIAL REQUIREMENTS Informal interaction and exchange of information among all program groups is expected. All awardees are expected to participate in an annual conference. Because of the need for rapid communication of data, the three dimensional coordinates of structures determined as part of this program must be available in the Protein Data Bank at the time of publication. The National Institute of General Medical Sciences places a limit of $4 million in direct costs over five years that may be requested on all program project grants. Amounts over this total may be requested for major pieces of equipment, extensive organic synthesis, or other exceptional needs. Such exceptions must be discussed prior to submission with Dr. James Cassatt at the address listed under INQUIRIES. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results >From the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations), which have been in effect since 1990. The new policy contains some provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. LETTER OF INTENT Prospective applicants are asked to submit, by November 18, 1996, 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 contained allows NIGMS staff to estimate the potential review workload and avoid conflicts of interest in establishing the review panel. The letter of intent is to be sent to Dr. James C. Cassatt at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS-398 (rev. 5/95) is to be used in applying for these grants. Applications kits are available at most institutional offices of sponsored research; from the Grants Information Office, Office of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714, email: ASKNIH@odrockm1.od.nih.gov; and from the NIH Program Director listed under INQUIRIES. The RFA label available in the application kit must be affixed to the bottom of the face page. 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 title of the application and the RFA number must 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 three signed, exact photocopies in one package to DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, SUITE 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 also be sent to Helen R. Sunshine, Ph.D. Office of Scientific Review Activities National Institute of General Medical Sciences 45 Center Drive, MSC-6200 Bethesda, MD 20892-6200 Applications must be received by December 18, 1996. If an application is received after that date, it will be returned to the applicant without review. The Division of Research Grants (DRG) 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 DRG 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 by DRG staff for completeness and by NIGMS for responsiveness. Incomplete and/or non-responsive applications will be returned to the applicant. It should not be assumed that a site visit will be conducted during the course of the review of any of these applications. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened in accordance with the standard NIH peer review procedures. As part of the initial merit review, all applications will receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed, assigned a priority score, and receive a second level review by the National Advisory General Medical Sciences Council. Review criteria for this RFA are the same as for individual research grants. In particular the following aspects will be stressed: o Quality and originality of the proposed research projects, and the qualifications of the individual project leaders; o Involvement of investigators having expertise in the appropriate scientific disciplines to provide the breadth needed for an integrated program; o Evidence of collaboration and interaction among all the groups named in the application; and o Experience and competence of the Principal Investigator in directing and overseeing a broad program of the type proposed. AWARD CRITERIA Awards will be made according to priority score availability of funds, and programmatic priorities. INQUIRIES Written and telephone inquiries concerning this RFA are strongly encouraged. Preapproval is required for all new applications that request over $500,000 direct cost in any given year as noted above. Inquiries regarding programmatic issues and requests for prior approval may be addressed to: James C. Cassatt, Ph.D. Division of Cell Biology National Institute of General Medical Sciences 45 Center Drive, MSC-6200 Bethesda, MD 10892 Telephone: (301) 594-0828 FAX: (301) 480-2004 Email: czj@cu.nih.gov For fiscal and administrative matters contact: Phyllis Finch National Institute of General Medical Sciences 45 Center Drive, MSC-6200 Bethesda, MD 20892 Telephone: (301) 594-5243 Email: finchp@gm1.nigms.nih.gov Schedule Letter of Intent Receipt Date: November 18, 1996 Applications Receipt Date: December 18, 1996 Initial Review: March-April 1996 Secondary Review: May 1996 Anticipated Award Date: July 1, 1996 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Assistance No. 93-821. Awards will be made under the authority of the Public Health Service Act, Title IV, Part A, (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. From owner-sci-resources@net.bio.net Tue Aug 06 23:00:00 1996 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA HL-96-013 - V25(26) 08/02/96 Date: 7 Aug 1996 16:34:21 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 651 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <4ub95t$h8e@net.bio.net> NNTP-Posting-Host: net.bio.net MITOCHONDRIAL DNA MUTATIONS IN HEART, LUNG AND BLOOD DISEASES NIH Guide, Volume 25, Number 26, August 2, 1996 RFA: HL-96-013 P.T. 34; K.W. 0760053, 0715040, 0715032, 0715165 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: January 24, 1997 Application Receipt Date: March 12, 1997 THIS RFA USES "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. THE FULL RFA INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS AND MUST BE USED WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS RFA. PURPOSE This initiative will foster research on molecular, cellular, genetic, and epidemiologic approaches to elucidate the role of mitochondrial DNA (mtDNA) mutations in heart, blood vessels, blood and lung diseases. Its goals are to define mechanisms by which mtDNA mutations cause tissue-specific, progressive diseases, and to elucidate the cause and effect relationships between alterations in this genome and pathological phenotypes. The ultimate purpose of this initiative is the development of effective strategies for prevention and treatment of cardiovascular, pulmonary, and hematologic disorders due to mitochondrial DNA mutations in humans. Although this Request for Applications (RFA) is sponsored by the National Heart, Lung, and Blood Institute (NHLBI), other Institutes and Centers of the NIH may also have an interest in mitochondrial research. Applications will be assigned to the most appropriate Institute/Center on the basis of established PHS referral guidelines. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), Mitochondrial DNA Mutations in Heart, Blood and Lung Diseases, is related to the priority areas of heart disease and stroke, diabetes and chronic disabling conditions, and environmental health. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. All current policies and requirements that govern the research grant programs of the NIH will apply to grants awarded under this RFA. Awards under this RFA to foreign institutions will be made only for research of very unusual merit, need, and promise, and in accordance with Public Health Service policy governing such awards. MECHANISM OF SUPPORT This RFA will use the NIH individual research project grant (R01) mechanism of support. Newly independent investigators who wish to apply are encouraged to consult with a program representative (see INQUIRIES below). Specific application instructions have been modified to reflect "MODULAR GRANT" and "JUST-IN-TIME" streamlining efforts being examined by the NIH. The "MODULAR GRANT" concept establishes specific modules (increments) in which direct costs may be requested as well as a maximum level for requested budgets. Only limited budgetary information is required under this approach. The "JUST-IN-TIME" concept allows applicants to submit certain information only when there is a possibility for an award. It is anticipated that these changes will reduce the administrative burden for the applicants, applicant institutions, reviewers, and Institute staff. For this RFA, funds must be requested in $25,000 direct cost modules. Up to a maximum of seven modules ($175,000 direct costs) per year may be requested. A feature of the modular grant concept is that no escalation is provided for future years, and all anticipated expenses for all years of the project must be included within the number of modules being requested. Only limited budget information will be required and any budget adjustments made by the Initial Review Group will be in modules of $25,000. Instructions for completing the Biographical Sketch have also been modified. In addition, Other Support information and the application Checklist page are not required as part of the initial application. If there is a possibility for an award, necessary budget, Other Support, and Checklist information will be requested by NHLBI staff following the initial review. The APPLICATION PROCEDURES section of this RFA provides specific details of modifications to standard PHS 398 application kit instruction. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for an application submitted in response to this RFA may not exceed four years. 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. It is anticipated that support for this program will begin in September 1997. Administrative adjustments in project period and/or amount may be required at the time of the award. FUNDS AVAILABLE It is anticipated that for fiscal year 1997, approximately $1,800,000 total costs will be available for the first year of support for this initiative. Award of grants pursuant to this RFA is contingent upon receipt of such funds for this purpose. It is anticipated that approximately six new grants will be awarded under this program. The specific number to be funded will, however, depend on the merit and scope of the applications received and on the availability of funds. Direct costs will be awarded in modules of $25,000, less any overlap or other necessary administrative adjustments. Indirect costs will be awarded based on the negotiated rates. RESEARCH OBJECTIVES Background There is now convincing evidence that proper functioning of human mitochondrial DNA (mtDNA) is critical to normal cellular metabolism and that mutations in mtDNA can result in severe disease phenotypes. Recently, a large number of mtDNA mutations have been catalogued and linked to human degenerative diseases. Mitochondrial defects may be inherited or acquired. Phenotypic abnormalities in individuals bearing genetic defects may be evident at birth or may not be apparent until middle age. Although it is clear that mutations in mtDNA can cause devastating symptoms affecting different organ systems, many clinically relevant questions concerning pathophysiology remain unanswered. Quantitative relationships between the abundance of mutated forms of mtDNA relative to normal mitochondrial genome and dysfunction of different cell types remain to be defined. In terms of cardiovascular diseases, evidence suggests that an accumulation of mutant forms of mtDNA in the myocardium frequently results in cardiac conduction block and sudden cardiac death. It is apparent that certain types of cardiac diseases may be caused by the mtDNA mutations, but the pathophysiological events that give rise to specific forms of heart disease in association with these mtDNA mutations still remain obscure. The current view is that abnormalities in mitochondrial structure and function, and mutations in mtDNA are associated with a large number of cardiac pathologies including ischemic heart disease, idiopathic dilated cardiomyopathy, hypertrophic cardiomyopathy, and cardiomyopathy of aging. However, strict causal relationships among abnormalities in mtDNA and/or abnormalities in mitochondrial biogenesis and these cardiac abnormalities are not fully elucidated. Resolution of this problem can come from study of animal models, which have not yet been developed. Such models will also provide the opportunity to test potential therapeutic strategies, including the development of mitochondrial gene therapy. Some studies suggest that abnormalities in mtDNA not only cause the rare but devastating syndromes that have been identified as mitochondrial diseases, but contribute to the pathophysiology of other widely prevalent diseases. A deficiency of mtDNA has been observed in HIV-infected patients treated with antiviral nucleoside analogues (ANA), and is proposed to contribute to myopathic symptoms in these individuals. Evidence suggests that short-term usage of ANA drugs is relatively safe; however, long term usage reveals that they can become toxic and affect oxidative phosphorylation, which appears to be attributable to a defect in mitochondrial replication. This defect resembles certain mitochondrial genetic diseases that have been associated with cardiomyopathy, mitochondrial myopathy, neuropathy, lactic acidosis, exocrine pancreas failure, pancreas failure, liver failure and bone marrow failure. It has been suggested that mitochondrial toxic ANAs may serve as experimental tools to clarify mtDNA replication. In the area of hematology, evidence for the association of mitochondrial DNA mutations and blood diseases is fragmentary. One exception is Pearson's syndrome, a progressive congenital disorder involving the hematopoietic system, exocrine pancreas, liver and kidneys. Within the blood, it is characterized by bone marrow failure, hypoproliferative sideroblastic anemia, and pancytopenia. It is associated with enzymatic deficiencies in some of the respiratory chain enzymes within blood cells that occur in conjunction with large-scale, single deletions of the mitochondrial genes encoding these enzymes. This is the first reported mitochondriopathy with a non-neuromuscular expression. The reported abnormalities of both erythroid and myeloid precursors in the arrow of Pearson's Syndrome patients suggests a potential role of mtDNA in hematopoiesis. Although Pearson's syndrome itself is relatively rare, it is certainly possible that other forms of sideroblastic or aplastic anemias may also be associated with acquired or inherited mtDNA mutations. Sideroblastic anemias in general have the unique characteristic of amorphous iron deposits in erythroblast mitochondria. The role of iron in mitochondria and the ineffective erythropoiesis in these anemias needs further study. Iron in red cell membranes has been reported in thalassemia and sickle cell disease. This iron deposition causes significant oxidation of membrane proteins in these disorders, but little has been reported on possible oxidative damage to mitochondria in the red blood cell precursors. In addition, little is known about possible mitochondrial damage in other diseases involving iron overload or in the blood of individuals undergoing chronic transfusion. Many dysfunctions of electron transport chain enzymes as well as mutant mtDNA have also been found in platelets and/or lymphocytes of patients with diseases associated with aging, including Parkinson's, Huntington's, and Alzheimer's diseases. Furthermore, this phenomenon has been reported in Down syndrome, which is characterized by an accelerated aging process. Some of these enzymatic dysfunctions have been linked to mutations in mitochondrial genes encoding these proteins. Most of these mutations have been discovered as a result of using blood cells because of their accessibility as a "diagnostic test" to screen for mutations that may also occur in tissues more directly involved in the disease, but are less accessible, such as brain tissue from Parkinson's Disease patients. It is quite possible that the function of the blood cells themselves may be affected by the mtDNA mutations. Elucidating how the bioenergetic defects in blood cells affect their own function may have implications for other diseases involving mtDNA mutations. The role of mutations in mtDNA in etiology and pathogenesis of lung disease is virtually unexplored. The lung might be particularly prone to mitochondrial DNA damage as a result of its oxidative environment, rapidly turning over epithelium, and constant exposure to environmental agents. The consequences on mtDNA of exposure of potential therapeutic agents such as nitric oxide are not understood. Damage or loss of specific mitochondrial genes associated with energy generation could potentially affect many aspects of pulmonary cell function, particularly under stressful conditions. Examples of lung cell functions that might be impaired include surfactant and extracellular matrix biosynthesis, cell repair processes, mucociliary transport, ion gradients, and neural control of airway smooth muscle function. Thus, one objective of future research should be to establish whether mtDNA damage occurs in the lung in association with disease states, and if so, to determine the role of mtDNA damage and repair in the etiology of lung disease. Although much of the evidence involving a link between mtDNA mutations and certain diseases is unequivocal, there is still a compelling need to determine the extent to which mtDNA mutations affect the natural history of heart, blood vessels, blood, and lung diseases. There have been few epidemiological studies of mitochondrial disorders and thus the extent of the problem in general populations is unknown. The attributable risk of myocardial, hypertensive, and other cardiovascular diseases due to mitochondrial gene mutations is also unknown. The lack of an easy screening test, other than the blood cell diagnostic test' mentioned above, which may miss certain types of mtDNA mutations, has hampered this research. However, maternal transmission of inherited mtDNA defects and the apparent mendelian pattern of inheritance for certain mtDNA deletions (implying nuclear gene involvement in mtDNA replication) suggests that pedigree studies could be informative. Family studies could be used to elucidate susceptibility markers and factors associated with phenotypic expression of mtDNA diseases. Preexisting population studies that have already collected DNA could assess mitochondrial DNA variation in a relatively cost-effective manner. Research Goals and Scope The following examples of potential research projects are given for illustrative purposes only and are not intended to define the scope of relevant topics. Investigators are expected to use their expert knowledge of the field in developing responses to this initiative o Establish animal and cellular models of mutant mtDNA relevant to heart, vascular, lung and blood disorders o Identify genes important for mtDNA replication or repair, segregation of mitochondrial genomes during cell division, and control of mtDNA copy numbers in cell types found in heart, vascular, lung and blood disorders o Develop methods to transfer exogenous genes into mammalian mitochondria or to complement mitochondrial gene defects by gene transfer to the nucleus of cardiovascular, lung and blood cells. o Establish mechanisms of damage in relationship to the etiology of the heart, vascular, lung and blood disease states in animals or humans o Elucidate mechanisms that promote mitochondrial DNA mutations in ischemic heart disease and hyperoxic lung disease. o Elucidate the role of mtDNA damage in early development of cardiovascular, lung and blood cells o Identify markers for susceptibility to mitochondrial diseases of heart, vascular, lung and blood and development of preventive strategies o Elucidate the reasons that some mitochondrial mutations and deletions give rise to clinically different heart, vascular, lung and blood disorders and some have no effect. o Elucidate quantitative relationships between mutant forms of mtDNA and heart and lung dysfunction. o Define the pathways for ATP synthesis and utilization changes in blood cells, cardiovascular, and lung tissues with defective mitochondrial genes. o Identify mtDNA determinants of heart, vascular, lung, and blood disease and risk factors. o Define the pathways for ATP synthesis and utilization changes in blood cells, cardiovascular and lung tissues with defective genes. SPECIAL REQUIREMENTS Upon initiation of the program, the NHLBI will sponsor periodic meetings to encourage exchange of information among investigators who participate in this program. In the budget for the grant application, applicants should request travel funds for a 1-day meeting each year, most likely to be held in Bethesda, Maryland. Applicants should also include a statement in their applications indicating their willingness to participate in these meetings. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results >From the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations), which have been in effect since 1990. The new policy contains some provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. LETTER OF INTENT Prospective applicants are asked to submit, by January 24, 1997, 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 NIH staff to estimate the potential review workload and avoid conflict of interest in the review. A faxed letter of intent may be used in place of a posted one. The letter of intent is to be sent to: Dr. C. James Scheirer Division of Extramural Affairs National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7220, MSC 7924 Bethesda, MD 20892-7924 Telephone: (301) 435-0266 FAX: (301) 480-3541 Email: James_Scheirer@NIH.GOV APPLICATION PROCEDURES The research grant application form PHS-398 (rev. 5/95) is to be used in applying for these grants. Applications kits are available at most institutional offices of sponsored research; from the Grants Information Office, Office of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714, email: ASKNIH@odrockm1.od.nih.gov; and from NHLBI program staff listed under INQUIRIES. The RFA label available in the application kit must be affixed to the bottom of the face page. 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 title of the application and the RFA number must 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 three signed, exact photocopies in one package to DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, SUITE 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) Submit an additional two copies of the application to Dr. Scheirer at the address listed under LETTER OF INTENT. It is important to send these two copies at the same time as the original and three copies are sent to the Division of Research Grants; otherwise, the NHLBI cannot guarantee that the application will be reviewed in competition for this RFA. Sample budgets and justification page will be provided upon request or following the submission of a letter of intent. BUDGET INSTRUCTIONS The total direct costs must be requested in accordance with the program guidelines and the modifications made to the standard PHS 398 application instructions described below: o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD Do not complete Form Page 4 of the PHS 398 (rev 5/95). It is not required nor will it be accepted at the time of application. o BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT Do not complete the categorical budget tables on Form page 5 of the PHS 398 (rev. 5/95). Only the requested total direct costs line for each year must be completed based on the number of $25,000 modules being requested. Applicants may not request a change in the amount of each module. A maximum of seven modules ($175,000 direct costs) per year may be requested and each applicant may request up to four years of support for this RFA. Direct cost budgets will remain constant throughout the life of the project (i.e. the same number of modules requested for all budget periods). Any necessary escalation should be considered when determining the number of modules to be requested. However, in the event that the number of modules requested must change in any future year due to the nature of the research proposed, appropriate justification must be provided. Total Direct Costs for the Entire Proposed Project Period should be shown in the box provided. o BUDGET JUSTIFICATION Budget justifications should be provided under "Justifications" on Form Page 5 of the PHS 398. List the names, role on the project and proposed percent effort for all project personnel (salaried or unsalaried)and provide a narrative justification for each person based on his/her role on the project. Identify all consultants by name and organizational affiliation and describe the services to be performed. Provide a general narrative justification for individual categories (equipment, supplies, etc.) required to complete the work proposed. More detailed justifications should be provided for high cost items. Any large one-time purchases, such as large equipment requests, must be accommodated within these limits. o CONSORTIUM/CONTRACTUAL COSTS - If collaborations or subcontracts are involved that require transfer of funds from the grantee to other institutions, it is necessary to establish formal subcontract agreements with each collaborating institution. A letter of intent >From each collaborating institution should be submitted with the application. Only the percentage of the consortium/contractual TOTAL COSTS (direct and indirect) relative to the total DIRECT COSTS of the overall project needs to be stated at this time. The following example should be used to indicate the percentage cost of the consortium, "The consortium agreement represents 27% of overall $175,000 direct costs requested in the first year.". A budget justification for the consortium should be provided as described in the "Budget Justification" section above (no Form Page 5 required for the consortium). Please indicate whether the consortium will be in place for the entire project period and identify any future year changes in the percentage relative to the parent grant. If there is a possibility for an award, the applicant will be requested to identify actual direct and indirect costs for all years of the consortium. Please note that total subcontract costs need not be calculated in $25,000 modules. However, when subcontract funds are added to the parent grant budget, the total direct cost amount must be included in the number of $25,000 modules requested. o BIOGRAPHICAL SKETCH - A biographical sketch is required for all key personnel, following the modified instructions below. Do not exceed the two-page limit for each person. Complete the educational block at the top of the form page; List current position(s) and those previous positions directly relevant to the application; List selected peer-reviewed publications directly relevant to the proposed project, with full citation; The applicant has the option to provide information on research projects completed and/or research grants participated in during the last five years that are relevant to the proposed project. o OTHER SUPPORT - Do not complete the "Other Support" pages (Form Page 7). Selected other support information relevant to the proposed research may be included in the Biographical Sketch as indicated above. Complete Other Support information will be requested by NHLBI staff if there is a possibility for an award. o CHECKLIST - No "Checklist" page is required as part of the initial application. A completed Checklist will be requested by NHLBI staff if there is a possibility for an award. o The applicant should provide the name and phone number of the individual to contact concerning fiscal and administrative issues if additional information is necessary following the initial review. Applications not conforming to these guidelines will be considered unresponsive to this RFA and will be returned without further review. Applications must be received by March 12, 1997. If an application is received after that date, it will be returned to the applicant without review. The Division of Research Grants (DRG) 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 DRG 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 re-viewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer-review group convened by the NHLBI in accordance with NIH peer-review procedures. As part of the initial merit review, all applications will receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed, assigned a priority score, and receive a second level review by the National Heart, Lung, and Blood Advisory Council. The personnel category will be reviewed for appropriate staffing based on the requested percent effort. The direct costs budget request will be reviewed for consistency with the proposed methods and specific aims. Any budgetary adjustments recommended by the reviewers will be in $25,000. The duration of support will be reviewed to determine if it is appropriate to ensure successful completion of the recommended scope of the project. Other review criteria will include: o scientific, technical or medical significance and originality of proposed research o appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research o qualifications and research experience of the Principal Investigator and staff, particularly, but not exclusively, in the area of the proposed research o availability of the resources necessary to perform the research. o adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. The initial review group will also examine the provisions for the protection of human and animal subjects and the safety of the research environment. AWARD CRITERIA Applications will compete for available funds with all other approved applications. The following will be considered in making funding decisions: quality of the proposed project as determined by peer-review, availability of funds, and program priority. INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Dr. Isabella Liang Division of Heart and Vascular Diseases National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Suite 9142, MSC 7940 Bethesda, MD 20892-7940 Telephone: (301) 435-0520 FAX: (301) 480-1335 Email: liangi@gwgate.nhlbi.nih.gov Dr. Carol Letendre Division of Blood Diseases and Resources National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Suite 10162, MSC 7950 Bethesda, MD 20892-7950 Telephone: (301) 435-0080 FAX: (301) 480-0867 Email: letendrc@gwgate.nhlbi.nih.gov Dr. Dorothy Gail Division of Lung Diseases National Heart, Lung, and Blood Institute Two Rockledge Center, Suite 10100 6701 Rockledge Drive, MSC 7952 Bethesda, MD 20892-7952 Telephone: 301-435-0222 Fax: 301-480-3557 Email: gaild@gwgate.nhlbi.nih.gov Ms. Phyliss Sholinsky Division of Epidemiology and Clinical Applications National Heart, Lung, and Blood Institute Two Rockledge Center, Suite 8151 6701 Rockledge Drive, MSC 7934 Bethesda, MD 20892-7934 Telephone: 301-435-0701 Fax: 301-480-1667 Email: sholinsp@gwgate.nhlbi.nih.gov Direct inquiries regarding fiscal matters and requests for sample budgets to: Ms. Marie Willett Grants Operations Branch National Heart, Lung, and Blood Institute Two Rockledge Center, Suite 7128 6701 Rockledge Drive, MSC 7926 Bethesda, MD 20892-7926 Phone: 301-435-0144 Fax: 301-480-3310 E-mail: willettm@gwgate.nhlbi.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.837, 93.838, and 93.839. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants' policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. From owner-sci-resources@net.bio.net Tue Aug 06 23:00:00 1996 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - PA-96-068 - V25(26) 08/02/96 Date: 7 Aug 1996 16:34:35 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 375 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <4ub96b$h91@net.bio.net> NNTP-Posting-Host: net.bio.net INNOVATIVE DRUG DISCOVERY RESEARCH IN AIDS OPPORTUNISTIC INFECTIONS NIH Guide, Volume 25, Number 26, August 2, 1996 PA NUMBER: PA-96-068 P.T. 34; K.W. 0715008, 0755025, 0765035, 0715125 National Institute of Allergy and Infectious Diseases Application Receipt Dates: January 2, May 1, September 1 PURPOSE The National Institute of Allergy and Infectious Diseases gives special consideration for funding to scientifically meritorious applications in response to Program Announcements. Program Announcements (PA) identify areas of ongoing research emphasis for the NIAID. The purpose of this PA is to seek research grant applications aimed at novel approaches to discovery and preclinical development of therapeutic agents and strategies against opportunistic infections (OIs) in people with AIDS. The intent of this Program Announcement is to encourage investigator-initiated grant applications that involve creative and original preclinical research that emphasizes under-exploited facets of the basic biology, biochemistry, and pathophysiology of the opportunistic pathogens necessary to propel advances in improved therapies. No clinical trials will be supported under this PA. Another Program Announcement, "Collaborations for Advanced Strategies in Opportunistic Infections," soliciting research projects that encompass laboratory research linked to proof-of-concept clinical studies will be announced at a later date. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000", a PHS-led national activity for setting priority areas. This PA, Innovative Drug Discovery Research for Opportunistic Infections Associated with AIDS, is related to the priority area of human HIV infection. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) (R29) awards. MECHANISM OF SUPPORT Traditional research project grant (R01), FIRST award (R29), small research (R03) grant, and Interactive Research Project Grants (IRPG), awards may be submitted in response to this PA. Applications for R01 grants may request up to five years of support. Applications for R29 grants must request five years of support and are limited to $350,000 in direct costs over the entire project period. The NIAID uses R03 grants to support small highly innovative or pilot projects. Applicants for R03 grants may request up to $50,000 (direct costs) per year for a period not to exceed three years. Funds and time requested should be appropriate for the research proposed. Applicants for R03 grants must follow the special application guidelines and Terms and Conditions of Award for NIAID SMALL RESEARCH GRANTS, which appeared in the NIH Guide for Grants and Contracts, Vol. 25, No. 9, March 22, 1996. If an IRPG is proposed, it must consist of a minimum of two independent applications (see PA-96-001, NIH Guide for Grants and Contracts, Vol. 24, No. 35, October 6, 1995). An IRPG may consist of a combination of R01s and R29s or R01s only, but may not consist solely of R29 applications. An IRPG may also contain shared interactive resources (Cores), which must serve at least two of the research projects in order to facilitate achievement of the Group's common research goals. Collaborative arrangements involving more than one institution are especially encouraged, including participation of the pharmaceutical industry where appropriate. RESEARCH OBJECTIVES Background The principal causes of morbidity and mortality in AIDS are opportunistic infections (OIs). Although HIV is the primary cause of the progressive immunological deterioration seen in AIDS, the OIs account for the vast majority of all AIDS-related deaths as well as diminishing quality of life. Individuals infected with HIV are susceptible to a range of viral, bacterial, protozoal, and fungal infections. The pathologic consequences associated with OIs in AIDS are debilitating oral lesions, retinitis (cytomegalovirus), progressive multifocal leukoencephalopathy (JC virus),, disseminated nontuberculosis mycobacterial disease (M. avium), pulmonary disease (Pneumocystis carinii), protracted diarrhea (Cryptosporidium parvum, Enterocytozoon bieneusi), and meningitis (Cryptococcus neoformans). Whereas the available treatments for OIs have improved and prolonged the lives of people living with AIDS, the management of OIs in AIDS patients remains difficult and complicated due to toxicity and adverse side effects of therapeutic agents, long-term drug use leading to patient intolerance or drug resistance, frequent relapses, drug-drug interactions, and/or lack of standard treatments for newly emerging OIs (e.g., JC virus, C. parvum, E. bieneusi). New ideas and novel approaches are urgently needed to overcome the lack of therapeutic options available to people with AIDS-associated OIs. Research Objectives and Experimental Approaches The principal objective of this PA is to stimulate drug discovery through original and innovative research focused on key metabolic and pathophysiologic features between pathogen and host that will lead to the discovery and development of safe, better tolerated and effective new therapies for AIDS-associated OIs. Equally important is the need for rapid, non-invasive detection methods for early and specific diagnosis and for evaluation of responses to therapy. Research responsive to this PA includes studies to identify therapies and evaluation strategies for the following infectious agents: human cytomegalovirus (HCMV), JC virus, Mycobacterium avium, Pneumocystis carinii, Cryptosporidium parvum, the Microsporida, and Cryptococcus neoformans. Areas of study on these organisms include, but are not restricted to, the following: o discovery of efficacious new antibiotics for treatment and prevention of AIDS-associated disease; o basic cellular and molecular biology of the pathogens (virulence factors, genome structure, and gene expression) leading to identification of potential new chemo-or immuno-therapeutic targets; o pathogen physiology, biochemistry and metabolism leading to a better understanding of drug susceptibility and resistance; o development of improved in vitro (cell culture) and in vivo (animal model) systems for drug evaluations; o identification and evaluation of promising new drugs from natural products and synthetic chemical compounds, and elucidation of their mechanism of action; o early development and preclinical validation/standardization of rapid, non-invasive diagnostic methods for the specific and quantifiable detection of the infectious organism and for monitoring response to therapy; o development of improved delivery systems for therapeutic agents. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results >From the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations), which have been in effect since 1990. The new policy contains some provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research", which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and printed in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 5/95). Applications kits are available at most institutional offices of sponsored research and may be obtained from the Grants Information Office, Office of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714, email: ASKNIH@odrockm1.od.nih.gov. Specific guidelines for R03 applications are provided in the notice, "NIAID Small Research Grants," NIH Guide, Vol. 25, No. 9, March 22, 1996; which is available from program staff listed under INQUIRIES. Specific guidelines for IRPG applications are provided in PA-96-001, NIH Guide, Vol. 24, No. 25, October 6, 1995. Specific guidelines for FIRST (R29) awards are provided in "First Award Guidelines (rev. 6/96). Applications for FIRST (R29) awards must include at least three sealed letters of reference attached to the face page of the original application. FIRST (R29) applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. Applications must be identified by checking "YES" on line 2 of the PHS face page, and the number and title of this program announcement must be typed in. Submit a signed, typewritten original of the application, including the Checklist, and five signed, exact photocopies in one package to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, SUITE 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) R03 applicants should submit an original typewritten application and three exact signed copies to the Division of Research Grants at the above address, and two copies to: Stanley Oaks, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C06 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7042 FAX: (301) 402-2638 Email: stanley_oaks@nih.gov Applicants from institutions that have a General clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the Center as a resource for conducting the proposed research. If so, a letter of agreement from the GCRC Program Director must be included in the application material. The Small Business Innovation Research Program (SBIR) and the Small Business Technology Transfer Research Program (STTR) also solicit applications in this research area. SBIR and STTR solicitation packages are available from: MTL, Inc. 13687 Baltimore Avenue Laurel, MD 20707-5096 Telephone: (301) 206-9385 FAX: (301) 206-9722 Email: a2y@cu.nih.gov The National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Dental Research (NIDR) also have interests in the basic biology, biochemistry, and pathophysiology of opportunistic pathogens; in particular, how these organisms interact with host lung cells and affect the respiratory system (NHLBI), or how they interact with tissues and defense mechanisms of the oral cavity (NIDR). Therefore, applications that are of mutual interest are likely to be given a secondary assignment to NHLBI or NIDR in accordance with the NIH referral guidelines. REVIEW CONSIDERATIONS R03 APPLICANTS ONLY: Review considerations and procedures are contained in the NIAID SMALL RESEARCH GRANTS notice which appeared in the NIH Guide for Grants and Contracts, Vol. 25, No. 9, March 22, 1996. Applications will be assigned on the basis of established PHS referral guidelines. Program staff will be responsible for determining whether an application is responsive to the goals of the PA. Applications will be reviewed for scientific and technical merit in accordance with the standard NIH peer review procedures. As part of the initial merit review, all applications may 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 appropriate national advisory council. Review Criteria o scientific, technical, or medical significance and originality of the proposed research; o appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; o interactive nature of the component and overall program of the IRPG (where applicable); o qualifications and research experience of the Principal Investigator and staff, particularly but not exclusively, in the area of the proposed research; o availability of the resources necessary to perform the research; o appropriateness of the proposed budget and duration in relation to the proposed research; o adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. The initial review group will also examine the provisions for the protection of human and animal subjects and the safety of the research environment. AWARD CRITERIA Applications will compete for available funds with all other favorably recommended applications. The following will be considered when making funding decisions: quality of the proposed project as determined by peer review, program balance among research areas of the announcement, availability of funds. INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic (eligibility, responsiveness, and choice of funding mechanism) issues to: Chris Lambros, Ph.D. Division of AIDS National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 2C40, MSC 7620 Bethesda, MD 20892-7620 Telephone: (301) 402-2304 FAX: (301) 402-3171 Email: chris_lambros@nih.gov R03 APPLICANTS ONLY: Direct inquiries regarding review issues and special instructions for application preparation to Dr. Stanley Oaks at the address listed under APPLICATION PROCEDURES. Direct inquiries regarding fiscal and administrative matters to: Ms. Jane W. Unsworth Division of Extramural Activities National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 4B25, MSC 7610 Bethesda, MD 20892-7610 Telephone: (301) 402-6824 FAX: (301) 480-3780 Email: jane_unsworth@nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalogue of Federal Domestic Assistance No. 93.856. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of the Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. From owner-sci-resources@net.bio.net Sun Aug 11 23:00:00 1996 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 25, no. 27, pt. 1of1, 9 August 1996 Date: 12 Aug 1996 13:43:37 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 576 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <4uo51p$3a4@net.bio.net> NNTP-Posting-Host: net.bio.net X-comment: RFAs described: HL-96-017, PA-96-069 X-URL: gopher://gopher.nih.gov:70/11/res/nih-guide/guide-files/96.08.09 NIH GUIDE - Vol. 25, No. 27 - August 9, 1996 $$INDEX BEGIN ******************************************************* NOTICES $$INDEX N1 ********************************************************** FINDINGS OF SCIENTIFIC MISCONDUCT Department of Health and Human Services INDEX: DEPARTMENT OF HEALTH AND HUMAN SERVICES $$INDEX N2 ********************************************************** BEHAVIORAL THERAPIES DEVELOPMENT PROGRAM - ADDENDUM National Institute on Drug Abuse INDEX: National Institute on Drug Abuse $$INDEX N3 ********************************************************** NATIONAL ANIMAL WELFARE EDUCATION WORKSHOPS National Institutes of Health INDEX: National Institutes of Health $$INDEX N4 ********************************************************** NATIONAL HUMAN SUBJECT PROTECTIONS WORKSHOPS National Institutes of Health Food and Drug Administration INDEX: NATIONAL INSTITUTES OF HEALTH; FOOD AND DRUG ADMINISTRATION NOTICES OF AVAILABILITY (RFPs/RFAs/PAs) $$INDEX R1 04/24/97 ************************************************* ETIOLOGY OF CARDIOVASCULAR COMPLICATIONS IN HIV INFECTION (RFA HL-96- 017) National Heart, Lung and Blood Institute INDEX: NATIONAL HEART, LUNG AND BLOOD INSTITUTE $$INDEX P1 ********************************************************** COLLABORATIONS FOR ADVANCED STRATEGIES IN OPPORTUNISTIC INFECTIONS (PA-96-069) National Institute of Allergy and Infectious Diseases INDEX: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES THE NIH GUIDE IS AVAILABLE ELECTRONICALLY VIA BITNET OR INTERNET, BY SUBSCRIPTION, AND IS ALSO ON THE NIH GOPHER (GOPHER.NIH.GOV) AND THE NIH WEBSITE (HTTP://WWW.NIH.GOV). ALTERNATIVE ACCESS IS THROUGH THE NIH GRANT LINE VIA MODEM (DATA LINE 301/402-2221); CONTACT DR. JOHN JAMES AT 301/435-2801 FOR DETAILS ON THE NIH GRANT LINE. THE PHS STRONGLY ENCOURAGES ALL GRANT AND CONTRACT RECIPIENTS TO PROVIDE A SMOKE-FREE WORKPLACE AND PROMOTE THE NON-USE OF ALL TOBACCO PRODUCTS. IN ADDITION, PUBLIC LAW 103-227, THE PRO-CHILDREN ACT OF 1994, PROHIBITS SMOKING IN CERTAIN FACILITIES (OR IN SOME CASES, ANY PORTION OF A FACILITY) IN WHICH REGULAR OR ROUTINE EDUCATION, LIBRARY, DAY CARE, HEALTH CARE OR EARLY CHILDHOOD DEVELOPMENT SERVICES ARE PROVIDED TO CHILDREN. THIS IS CONSISTENT WITH THE PHS MISSION TO PROTECT AND ADVANCE THE PHYSICAL AND MENTAL HEALTH OF THE AMERICAN PEOPLE. ALL COMPETING GRANT APPLICATIONS SUBMITTED TO THE NATIONAL INSTITUTES OF HEALTH MUST BE SENT TO: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) THE GRANTS INFORMATION OFFICE, DRG, HAS BEEN INCORPORATED INTO THE NEW OFFICE OF EXTRAMURAL OUTREACH & INFORMATION RESOURCES, OFFICE OF EXTRAMURAL RESEARCH, OFFICE OF THE DIRECTOR, NIH. REQUESTS FOR APPLICATION FORMS, PUBLICATIONS, AND OTHER INFORMATION MAY BE DIRECTED TO THE FOLLOWING: OFFICE OF EXTRAMURAL OUTREACH & INFORMATION RESOURCES NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, MSC 7910 BETHESDA, MD 20892-7910 TELEPHONE: (301) 435-0714 EMAIL: ASKNIH@ODROCKM1.OD.NIH.GOV $$INDEX END ********************************************************* NOTICES $$N1 BEGIN ********************************************************** FINDINGS OF SCIENTIFIC MISCONDUCT NIH GUIDE, Volume 25, Number 27, August 9, 1996 P.T. 34; K.W. 1014004, 1014006 Department of Health and Human Services Notice is hereby given that the Office of Research Integrity (ORI) has made final findings of scientific misconduct in the following case: Yahya Abdulahi, Ph.D., Clark Atlanta University: Based on its review of a report from the institution and ORI's own analysis, ORI found that Yahya Abdulahi, former Research Scientist, Department of Biology, Clark Atlanta University, committed scientific misconduct by plagiarizing words and concepts from a publication in the "Journal of Environmental Health" and by misrepresenting data in sections of a Public Health Service (PHS) grant application. Specifically, Dr. Abdulahi's grant application contains extensive and significant plagiarism in the "Description," "Background and Significance," "Experimental Design and Methods," and "Literature Cited" sections and contains plagiarism and misrepresentation of data in the "Preliminary Studies" section. Dr. Abdulahi's actions were serious in that (1) the plagiarism involved the use of extensive sections of a publication without attribution; (2) the materials, as plagiarized in the grant application, included misrepresented data; (3) the plagiarism included expropriation of the concept of the study in the publication; and (4) the plagiarism persisted throughout important portions of Dr. Abdulahi's grant application. Dr. Abdulahi has entered into a Voluntary Exclusion Agreement with ORI in which he has voluntarily agreed, for the three year period beginning July 16, 1996, to exclude himself from: (1) any contracting or subcontracting with any agency of the United States Government and from eligibility for, or involvement in, nonprocurement transactions (e.g., grants and cooperative agreements) of the United States Government as defined in 45 C.F.R. Part 76 (Debarment Regulations), and (2) serving in any advisory capacity to the Public Health Service (PHS), including but not limited to service on any PHS advisory committee, board, and/or peer review committee, or as a consultant. No publications were required to be corrected as part of this Agreement. INQUIRIES For further information, contact: Director, Division of Research Investigations Office of Research Integrity 5515 Security Lane, Suite 700 Rockville, MD 20852 Telephone: (301) 443-5330 $$N1 END ************************************************************ $$N2 BEGIN ********************************************************** BEHAVIORAL THERAPIES DEVELOPMENT PROGRAM - ADDENDUM NIH GUIDE, Volume 25, Number 27, August 9, 1996 PA NUMBER: PA 94-078 P.T. 34; K.W. 0415001, 0404009, 0404000 National Institute on Drug Abuse PURPOSE This notice is an addendum, Innovative Stage 1 Behavioral Therapy Development Research, to program announcement PA-94-078, published in the NIH Guide, Vol. 22, No. 26, July 15, 1994. The purpose of this addendum is to encourage Stage 1 research on the development of new and innovative behavioral interventions for the treatment of drug addiction and the prevention or reduction of HIV risk behaviors in drug abuse treatment populations. The translation of basic behavioral science research into creative new behavioral therapies for drug addicts is the ultimate goal of this program announcement. The National Institute on Drug Abuse (NIDA) is supporting the study of behavioral therapies (including, but not limited to, psychotherapy, behavior therapy, cognitive therapy, family therapy, skills training, and counseling approaches) that will potentially have a significant impact on reducing drug abuse and addiction and reducing HIV/AIDS risk behaviors. For those investigators applying for grants under the Behavioral Therapies Development Program, this notice is meant to supplement Program Announcement PA-94-078, which is still in effect and should be consulted in conjunction with this addendum. RESEARCH OBJECTIVES Behavioral interventions remain the most common, and sometimes the only, treatments administered to individuals with drug use disorders. Many of these interventions or therapies have been shown to have some efficacy in promoting initial abstinence from drugs, reducing relapse, decreasing total drug use, or decreasing HIV risk behaviors. Nonetheless, many questions remain about the best ways to intervene behaviorally in the treatment of addiction, and for some individuals, existing behavioral interventions may not be sufficient. Developments in basic behavioral science could have a positive impact upon the development of behavioral therapies. However, emerging scientific knowledge does not always get rapidly incorporated into the behavioral therapy development process. The objectives of this announcement are to encourage research, based upon emerging basic behavioral research findings, on the development of: (1) creative new therapies for drug use disorders and (2) innovative behavioral approaches to HIV risk reduction in drug abusing populations. This Stage 1 research ultimately involves the translation of ideas from basic behavioral science into clearly defined behavioral interventions/therapies for individuals with addictive disorders. Innovative research is needed that is not only based upon basic behavioral research, but also incorporates basic behavioral research into the Stage 1 effort. Such novel developmental therapy/intervention research may build upon research from the following (and other) areas of basic behavioral science: o Cognition and decision-making o Learning and motivation o Behavior analysis o Developmental psychology o Personality and individual differences o Social psychology Creative Stage 1 research that is theoretically-driven and solidly based in any area of basic behavioral science is sought. Applicants may propose behavioral therapy/intervention studies aimed at drug addiction treatment, HIV risk reduction in treatment populations, or both. All applications must be submitted on the grant application form PHS 398 (rev. 5/95) using the standard receipt dates described in the form. INQUIRIES Direct inquiries regarding this addendum and program announcement PA- 94-078 to: Lisa Onken, Ph.D. Division of Clinical and Services Research National Institute on Drug Abuse 5600 Fishers Lane, Room 10A-10 Rockville, MD 20857 Telephone: (301) 443-0107 Email: lo10n@nih.gov $$N2 END ************************************************************ $$N3 BEGIN ********************************************************** NATIONAL ANIMAL WELFARE EDUCATION WORKSHOPS NIH GUIDE, Volume 25, Number 27, August 9, 1996 P.T. 42; K.W. 0201011, 1014003 National Institutes of Health The National Institutes of Health (NIH), Office of Extramural Research (OER), Office for Protection from Research Risks (OPRR) is continuing to sponsor workshops on implementing the Public Health Service Policy on Humane Care and Use of Laboratory Animals. Each of the workshops scheduled for Fiscal Year 1996 will focus on a specific theme. The workshops are open to institutional administrators, members of Institutional Animal Care and Use Committees, laboratory animal veterinarians, investigators and other institutional staff who have responsibility for high-quality management of sound institutional animal care and use programs. Ample opportunities will be provided to exchange ideas and interests through question and answer sessions and informal discussions. DATES: September 19-20, 1996 TOPIC: The 1996 Guide for the Care and Use of Laboratory Animals: The Era of Performance Based Standards LOCATION: Adams Park Hotel, 1550 Court Place, Denver, CO 80202, telephone (303) 893-3333, FAX (303) 623-0303 SPONSORS: University of Colorado Health Sciences Center, Denver, CO; University of Southern Colorado, Pueblo, CO CONTACT: Ms. Joann Bauer or Dr. James O. Stevens Continuing Medical Education Office University of Colorado Health Sciences Center 4200 East 9th Avenue, Campus Box C295 Denver, CO 80262 Telephone: (303) 372-9054 or (303) 270-4648 FAX: (303) 372-9065 REGISTRATION FEE: $175.00 INQUIRIES For further information concerning future NIH/OPRR Animal Welfare Education Workshops, contact: Ms. Darlene Marie Ross Office for Protection from Research Risks National Institutes of Health 6100 Executive Boulevard, Suite 3B01 - MSC 7507 Rockville, MD 20892-7507 Telephone: (301) 496-8101 x233 Email: RossD@od6100m1.od.nih.gov $$N3 END ************************************************************ $$N4 BEGIN ********************************************************** NATIONAL HUMAN SUBJECT PROTECTIONS WORKSHOPS NIH GUIDE, Volume 25, Number 27, August 9, 1996 P.T. 42; K.W. 0783005 National Institutes of Health Food and Drug Administration The National Institutes of Health (NIH) and the Food and Drug Administration (FDA) are continuing to sponsor a series of workshops on responsibilities of researchers, Institutional Review Boards (IRBs), and institutional officials for the protection of human subjects in research. The workshops are open to everyone with an interest in research involving human subjects. The meetings should be of special interest to those persons currently serving or about to begin serving as a member of an IRB. Issues discussed at these workshops are relevant to all other Public Health Service agencies. The current schedule includes the following: DATES: September 26-27, 1996 TITLE: Role of the IRB in Collaborative Research LOCATION: Jumer's Castle Lodge, Peoria, IL SPONSORS: University of Illinois College of Medicine at Peoria, Peoria, IL; Meharry Medical College, Nashville, TN REGISTRATION: Ms. Nancy Hibser IRB/OPRR/FDA/Conference University of Illinois College of Medicine at Peoria One Illini Drive P.O. Box 1649 Peoria, IL 61656-1649 Telephone: (309) 671-8437 FAX: (309) 671-8513 REGISTRATION FEE: $125 ($135 after September 16, 1996) DESCRIPTION: The biomedical and behavioral research currently being conducted within academic institutions promises exciting advances in scientific knowledge, as well as unprecedented opportunities for the betterment of individual and society life. Increasingly, however, these dramatic achievements and opportunities are accompanied by scientific, ethical, regulatory, and legal intricacies, and dilemmas. Within the academic community, understanding these rapidly changing complexities is central to the Institutional Review Board's (IRB) ability to protect the rights and welfare of human research subjects while supporting scientific endeavor and its potential benefits to humankind. This conference is designed to examine a broad range of contemporary scientific, ethical, regulatory, and legal issues relating to biomedical, social behavioral, and anthropological research involving human subjects. Each of these issues will be discussed within the framework of the academic research environment, and presentations will focus on the unique challenges presented to (IRBs). Designed for both experienced and novice participants, the workshop will provide opportunities for greater depth and specificity on contemporary IRB issues. Along with sessions examining common IRB issues - including liability, informed consent, and deception - the conference will feature special focus sessions on issues related to historical perspectives, issues in mental health, the establishment, structure, and management of IRBs, computerized management information systems for the IRB office, FDA regulations for clinical trials, guidelines on inclusion of minorities and women, research involving special population, including children and elderly research subjects. Guest speakers will include representatives from OPRR: Mr. F. William Dommel, Jr., J.D., Dr. Kammal K. Mittal, and Ms. Darlene M. Ross; FDA: Dr. Gary L. Chadwick, Mr. Paul Goebel, Jr., Dr. Michael Norcross; NIMH: Dr. Andrea Baruchin. Distinguished members of the academic and clinical research community will also be present, including: Dr. Patricia Finn, St. Jude Children's Hospital at Memphis; Dr. Ernest Prentice, University of Nebraska; and co-host Dr. John Estrada, Meharry Medical College. The format will encourage audience participation and informational exchanges, with question and answer sessions throughout the program. INQUIRIES For further information regarding these workshops or future NIH/FDA National Human Subject Protections Workshops, contact: Ms. Darlene Marie Ross Office for Protection from Research Risks National Institutes of Health 6100 Executive Boulevard, Suite 3B01 - MSC 7507 Rockville, MD 20892-7507 Telephone: (301) 496-8101 x233 FAX: (301) 402-0527 Email: RossD@od6100m1.od.nih.gov $$N4 END ************************************************************ NOTICES OF AVAILABILITY (RFPs/RFAs/PAs) $$R1 BEGIN HL-96-017 FULL-TEXT ************************************** ETIOLOGY OF CARDIOVASCULAR COMPLICATIONS IN HIV INFECTION NIH GUIDE, Volume 25, Number 27, August 9, 1996 RFA AVAILABLE: HL-96-017 P.T. 34; K.W. 0715040, 0715008, 0755030 National Heart, Lung and Blood Institute Letter of Intent Receipt Date: February 1, 1997 Application Receipt Date: April 24, 1997 PURPOSE This solicitation is intended to foster fundamental research into the mechanisms responsible for the cardiovascular dysfunction and disease that has been seen in HIV+ patients. Investigations may be conducted on cells, tissues or whole animals, including those that have been genetically altered. The purpose is to develop understanding of the role of virus, viral proteins, immune cells, cytokine production, growth factor expression and co-infection with other pathogens in the altered function and disease manifestations of the cardiovascular system. It is anticipated that in FY 97 approximately $1.5 million total cost will be available to support four to six research project grant (R01) applications. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Etiology of Cardiovascular Complication of HIV Infection, is related to the priority area of HIV infection. Potential applicants may obtain a copy of "Healthy People 2000," (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington DC 20402-9325 (telephone 202-512-1800). INQUIRIES The RFA, which describes the research objectives, application procedures, review considerations, and award criteria for this solicitation, may be obtained electronically through the NIH Grant Line (data line 301/402-2221), the NIH GOPHER (gopher.nih.gov), and the NIH Website (http://www.nih.gov), and by mail and email from the program contact listed below. Dr. Constance Weinstein Division of Heart and Vascular Diseases National Heart, Lung and Blood Institute 6701 Rockledge Drive, Suite 9044, MSC 7940 Bethesda MD 20892-7940 Telephone: (301) 435-0510 FAX: (301) 480-1335 Email: WEINSTEC@GWGATE.NHLBI.NIH.GOV $$R1 END ************************************************************ $$P1 BEGIN PA-96-069 FULL-TEXT ************************************** COLLABORATIONS FOR ADVANCED STRATEGIES IN OPPORTUNISTIC INFECTIONS NIH GUIDE, Volume 25, Number 27, August 9, 1996 PA AVAILABLE: PA-96-069 P.T. 34; K.W. 0715008, 0715125, 0785035, 0745020, 0745027 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Dates: September 16, 1996; August 1, 1997; August 2, 1998 Application Receipt Dates: October 25, 1996; September 1, 1997; September 1, 1998 PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID) gives special consideration for funding to scientifically meritorious applications that propose research that would meet the objectives and program priorities that have been described in a Program Announcement. Program Announcements identify areas of ongoing research emphasis for the NIAID. The Opportunistic Infection Research Branch (OIRB) of the Therapeutics Research Program in the Division of AIDS (DAIDS), NIAID, invites applications for Collaborations for Advanced Strategies in Opportunistic Infections (CASOI). The purpose of this Program Announcement (PA) is to expand the clinical knowledge of opportunistic infections in people with AIDS by expediting the translation of promising innovative preclinical findings into clinical research applications. This PA announces the interest of the NIAID in supporting focused collaborative research between preclinical and clinical scientists to test, refine, and improve diagnostic, pathogenic, or therapeutic concepts leading to innovative approaches for the prevention and management of opportunistic infections (OIs) in individuals infected with HIV. This type of collaborative research would be dedicated to the expedited development and use of advanced preclinical findings into clinical applications. The opportunistic pathogens emphasized in this PA are Mycobacterium avium, Cryptosporidium parvum, and cytomegalovirus. Because the NIAID would like to fund more research in this area, the NIAID announces the intent to give special funding consideration to applications for integrated, multidisciplinary, translational research activities that use molecular or cellular approaches to: o develop and clinically validate innovative methods for detection of opportunistic infection; o elucidate the mechanisms of the human host-pathogen relationship in opportunistic infections; o develop innovative approaches to measure response to treatment in HIV-infected individuals; and/or o develop innovative strategies for the prevention or treatment of opportunistic infection. Research projects that principally encompass preclinical laboratory research are not within the area of interest of this PA, but may be within the areas of programmatic emphasis described in PA-96-068, "Innovative Drug Discovery Research in AIDS Opportunistic Infections," published in the NIH Guide, Vol 25, No. 26, August 2, 1996. Applications that include collaborations with the private sector (e.g., pharmaceutical, chemical, or biotechnological companies) are strongly encouraged. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This PA, Collaborations for Advanced Strategies in Opportunistic Infections (CASOI), is related to the priority area of HIV infection. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-0325 (telephone 202/512-1800). INQUIRIES The PA, which describes the research objectives, application procedures, review considerations, and award criteria for this solicitation, may be obtained electronically through the NIH Grant Line (data line 301/402-2221), the NIH GOPHER (gopher.nih.gov), and the NIH Website (http://www.nih.gov), and by mail and email from the program contact listed below. Barbara Laughon, Ph.D. Division of AIDS National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 2C26 - MSC 7620 Bethesda, MD 20892-7620 Rockville, MD 20852 (for express/courier service) Telephone: (301) 402-2304 FAX: (301) 402-3171 Email: barbara_laughon@nih.gov $$P1 END ************************************************************ From owner-sci-resources@net.bio.net Sun Aug 11 23:00:00 1996 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA HL-96-017 - V25(27) 08/09/96 Date: 12 Aug 1996 13:43:54 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 625 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <4uo52a$3av@net.bio.net> NNTP-Posting-Host: net.bio.net ETIOLOGY OF CARDIOVASCULAR COMPLICATIONS IN HIV INFECTION NIH GUIDE, Volume 25, Number 27, August 9, 1996 RFA: HL-96-017 P.T. 34; K.W. 0715040, 0715008, 0755030 National Heart, Lung and Blood Institute Letter of Intent Receipt Date: February 1, 1997 Application Receipt Date: April 24, 1997 THIS RFA USES "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. THE FULL RFA INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS AND MUST BE USED WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS RFA. PURPOSE This solicitation is intended to foster fundamental research into the mechanisms responsible for the cardiovascular dysfunction and disease that has been seen in HIV+ patients. Investigations may be conducted on cells, tissues or whole animals, including those that have been genetically altered. The purpose is to develop understanding of the role of virus, viral proteins, immune cells, cytokine production, growth factor expression and co-infection with other pathogens in the altered function and disease manifestations of the cardiovascular system. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000,"a PHS-led national activity for setting priority areas. This Request for Applications (RFA), Etiology of Cardiovascular Complications in HIV Infection, is related to the priority area of HIV Infection. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No.017-001-00473-1) through the Superintendent of Documents,Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. All current policies and requirements that govern the research grant programs of the NIH will apply to grants awarded under the RFA. Awards under this RFA to foreign institutions will be made only for research of very unusual merit, need, and promise, and in accordance with Public Health Service policy governing such awards. Among the disciplines and expertise that may be appropriate for this research program are cell biology, molecular biology, biochemistry, genetics, immunology, pathology, virology and physiology. MECHANISM OF SUPPORT This RFA will use the NIH individual research project grant (R01) mechanism of support. However, specific application instructions have been modified to reflect "MODULAR GRANT" and "JUST-IN-TIME" streamlining efforts being examined by the NIH. The modular grant concept establishes specific modules in which direct costs may be requested as well as a maximum level for requested budgets. Only limited budgetary information is required under this approach. The just-in-time concept allows applicants to submit certain information only when there is a possibility for an award. It is anticipated that these changes will reduce the administrative burden for the applicants, applicant institutions, reviewers and Institute staff. For this RFA, funds must be requested in $25,000 direct cost modules and a maximum of ten modules ($250,000 direct costs) per year may be requested. A feature of the modular grant concept is that no escalation is provided for future years, and all anticipated expenses for all years of the project must be included within the number of modules being requested. Only limited budget information will be required and any budget adjustments made by the Initial Review Group will be in modules of $25,000. Instructions for completing the Biographical Sketch have also been modified. In addition, Other Support information and the application Checklist page are not required aspart of the initial application. If there is a possibility for an award, necessary Budget, Other Support and Checklist information will be requested by NHLBI staff following the initial review. The APPLICATION PROCEDURES section of the RFA provides specific details of modifications to the standard PHS 398 application kit instructions. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. FUNDS AVAILABLE It is anticipated that for fiscal year 1997, approximately $1.5 million total costs will be available for the first year of support for this initiative. Award of grants pursuant to this RFA is contingent upon receipt of such funds for this purpose. It is anticipated that approximately four to six new grants will be awarded under this program. Applicants may request up to five years of support. The specific number to be funded will, however, depend on the merit and scope of the applications received and on the availability of funds. Direct costs will be awarded in modules of $25,000 less any overlap or other necessary administrative adjustments. Indirect costs will be awarded based on the negotiated rates. RESEARCH OBJECTIVES Background The incidence of HIV-infected patients suffering cardiac complications is unknown. Estimates vary considerably, depending upon geographical location, patient population and diagnostic procedures. Conservatively, it is estimated that about six percent to seven percent of HIV-infected adult patients have clinically significant heart disease, and a larger proportion, possibly as high as 18 percent, have clinically silent abnormalities. The two most common forms of HIV-related symptomatic cardiac disease are cardiomyopathy and pericardial effusion associated with cardiac tamponade. Left ventricular dysfunction occurs in all age groups including children and appears to increase when circulating CD4 cell counts are severely depressed. Left ventricular diastolic dysfunction has been reported in asymptomatic and symptomatic patients infected with HIV. HIV-infected intravenous drug users may develop severe cardiomyopathy and congestive heart failure with less CD4 cell depression than HIV patients who do not use drugs. Autopsy studies reveal a high prevalence of lymphocytic infiltrates in the hearts of AIDS patients, even though death may have been due to causes unrelated to cardiac disease, and some of these patients were not noted to have had symptomatic cardiac disease. In a meta-analysis of 402 cases, 46 percent were found to have histological evidence of myocarditis, yet a pathogenic viral, bacterial, or fungal agent was confirmed in only one out of five cases. There has been one report of significant coronary artery lesions in eight young HIV-infected patients who were found dead in unexplained circumstances. None of these patients had a family history of hypercholesterolemia, hypertension, or diabetes. The percentages of cardiac abnormalities are much higher in children infected with HIV. In one study of 81 patients, 64 percent were noted to have resting sinus tachycardia, and 11 percent sinus bradycardia. Dysrhythmias occurred in 35 percent, cardiorespiratory arrest occurred in 9 percent and 10 percent had chronic heart failure. In 12 percent, death was associated with marked cardiac dysfunction. Taking the Public Health Service estimate of 350,000 U.S. AIDS cases by the year 2000 and assuming a 6 percent rate of development of symptomatic heart disease in adults, a total of 21,000 HIV+ patients will require specialized cardiac care. The number will be very much larger worldwide. The susceptibility of cells within the heart to infection from HIV is undefined, as are possible mechanisms of indirect effects of HIV on the cardiovascular system. Research focused on the etiology and pathophysiology of cardiac disease in these patients could lead to improved treatment strategies and prevention of the onset of cardiovascular disease. Investigations of the etiology of cardiac complications in HIV-infected patients are confounded by a variety of factors, including drug use, the large number of self-prescribed medications, problems of nutrition, intercurrent illnesses, and of course, medications prescribed by the physician. For children with vertically transmitted HIV, the aforementioned factors may have affected the in utero environment. In addition, questions remain regarding: the effects of in utero infection; the possibility of increased susceptibility of immature and growing cells of the fetus and infant to HIV infection; and abnormal expression of growth factors and cytokines. For these reasons, it is proposed to study the effects of HIV on the cardiovascular system in animal models, in terms of a direct role and of an indirect role via expression of viral proteins, dysregulation of the immune system, cytokine expression and the pathogenicity of other infectious agents. In general, the role of viruses in the etiology of cardiac disease is poorly understood. Theories include injury as a result of viral infection of cardiac cells, apoptosis, myocytolysis as a consequence of a T-cell response to virus infected myocytes, autoimmune responses which target normal and infected myocytes, and cytokine and growth factor mediated dysfunction and injury. Susceptibility to inflammation may involve a genetic component. Similar speculations have been advanced for the occurrence of cardiac disease in HIV-infected patients. Thus, study of the role of HIV in cardiac complications might well lead to an overall advance in understanding the immunopathological mechanisms of cardiac injury resulting from infection by cardiotropic viruses and provide the basis for rational therapeutic strategies. One approach to understanding some of the mechanisms of dysfunction and disease of various organs and tissues seen in AIDS patients is to examine the role of various gene products by constructing transgenic mice, possibly with cardiotropic promoters. Several attempts have been made in organs and tissues other than heart, using various strains of mice, including SCID mice. This latter model may be useful in studying the role of immunodeficiency in the development of cardiac dysfunction and as an approach to cardiac disease in pediatric patients with HIV infection. Transgenic mice containing the complete HIV coding sequences fused to the mouse mammary tumor virus long terminal repeat have been generated. These mice produce gag and env HIV proteins in organs such as mammary gland, spleen and liver. In some transgenic lines, low levels of HIV proteins could also be detected in serum. The report states that animals sacrificed at 17 months of age were indistinguishable from non-transgenic mice on macroscopic and histologic examination. Thus, it would appear that cells from various tissues in the mouse are capable of replicating retroviruses and producing HIV proteins without causing disease. However, the heart was not among the tissues examined. Transgenic mice expressing the entire HIV genome under the control of the promoter for the human neurofilament NF-L gene exhibited neuropathological changes 7 to 12 months after birth. HIV was expressed in the neurons of these mice in contrast to the findings in humans where neurons are only rarely found to be infected with HIV. However, there were parallels between the hypoactivity of these mice and the psychomotor slowing and apathy seen in the early stages of AIDS dementia. These experiments suggest that disease may be caused not by the replication of the virus but by other related factors. Of more specific relevance is the transgenic mouse constructed to investigate the pathogenesis of HIV-associated nephropathy which occurs in about 10 percent of HIV-infected patients. The mice were made transgenic for a subgenomic proviral HIV construct, pNL4-3:d1443, which lacks the gag and pol genes and is therefore non-infectious. Abnormal renal histology was noted beginning at about 35 to 45 days of age. About 20 percent of these animals developed cardiac lesions at the base of the aortic valve, an adventitial process with macrophage and neutrophil infiltrates. Vasculitis involving the coronary arteries was also observed. The interesting aspect of this proviral construct was that its expression in heart tissue could not be detected by Northern analysis, although low level expression would only be detected by more sensitive methods. However, there was increased expression of atrial natriuretic factor, a molecular marker of myocyte hypertrophy, in the ventricles of these mice. One line of these transgenic mice carrying a subgenomic HIV proviral construct lacking the gag and pol genes was found to develop proliferative epidermal lesions with some similarities to those seen in HIV-infected patients. Dermal lesions similar to Kaposi's sarcoma were not seen in this model, in contrast to those seen in an HIV LTR-tat transgenic mouse. Thus, the proteins expressed by the genes appear to play an important role in pathogenesis of skin disorders in HIV-infected patients. There have been a few reports of the detection of HIV transcripts in endomyocardial biopsies of HIV-infected patients, but the significance of these findings is unclear since the transcripts have been detected in cardiac tissues of patients with and without known cardiac dysfunction. This leads to the speculation that viral proteins, immune mechanisms and cytokine and growth factor dysregulation might be implicated in the pathogenesis of cardiac dysfunction. It is possible that host genetic susceptibility may also play a role since it has been shown that, in mice infected with CVB3, macrophage inflammatory protein (MIP-l-alpha) is an absolute requirement for development of myocarditis. It is also possible that the constant, repeated cycles of viral replications lead to mutations with differential pathogenic effects which result in neurologic, kidney, or heart disease, or cancer. While some studies may be performed on cells, organs or whole animals, many will require the development and exploitation of transgenic animal models which could contribute to knowledge of the pathogenesis of cardiac complications in patients with HIV infection. However, because the presence of virus or viral proteins in a tissue does not necessarily induce dysfunction or disease and because cardiac dysfunction can occur in the absence of gross abnormalities it is important to evaluate these animals in terms of physiologic function and pathology of the cardiac disorders. Although not yet applied to the study of HIV-associated cardiac disorders, it has been demonstrated recently that microsurgical techniques can be used to study systolic and diastolic abnormalities that occur in transgenic mice. The use of such techniques has provided valuable mechanistic information regarding adrenergic signaling and calcium handling mechanisms that regulate ventricular function in vivo. These experiments suggest that similar approaches could be used to study relevant issues of ventricular dysfunction associated with HIV infection. Research Objectives and Scope The following items are provided as examples only. Applicants are urged to consider other projects within the scope of this solicitation based on their knowledge of the field and their expertise. Development of animal models is encouraged but preliminary data must be provided to indicate that the model will have relevance to the research requested. o Interaction of viral proteins with cardiovascular cells and the effects on cardiac function in HIV infection o Examination of circulating antibodies for cross-reactivity with cardiac tissue in HIV infection o Elucidation of the role of endothelium in the cardiovascular complications of HIV infection o Role of the immune system and cytokine production in the etiology of cardiac dysfunction in HIV infection o Evaluation of ventricular function and myocyte contractility in transgenic mice that exhibit neuropathologic changes in HIV-related studies o Investigations in cell culture and whole heart of the mechanisms whereby HIV infection perturbs the contractile function of the myocardium o Identification of the mechanisms whereby HIV mediates disorders of impulse generation, conduction and EC coupling o Investigations of the alterations of gene expression of cardiac contractile proteins, calcium regulatory proteins, and markers of ventricular hypertrophy such as ANF in HIV-related complications o The role of coinfection with other pathogens, such as cytomegalovirus, which have been implicated in HIV cardiomyopathy. SPECIAL REQUIREMENTS Upon initiation of the program, the NHLBI will sponsor periodic meetings to encourage exchange of information among investigators who participate in this program. Travel funds for a one day meeting each year, most likely to be held in Bethesda, Maryland should be included in the modules. Applicants should also include a statement in their applications indicating their willingness to participate in these meetings. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results >From the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations), which have been in effect since 1990. The new policy contains some provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 20, 1994 (FR 59 14508-14513) and reprinted in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. LETTER OF INTENT Prospective applicants are asked to submit, by February 1, 1997, 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 NHLBI staff to estimate the potential review workload and avoid conflict of interest in the review. The letter of intent is to be sent to: Dr. C. James Scheirer Division of Extramural Affairs National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7220, MSC 7924 Bethesda, MD 20892-7924 Telephone: (301) 435-0266 FAX: (301) 480-3541 Email: James_Scheirer@NIH.GOV APPLICATION PROCEDURES The research grant application form PHS 398 (rev.5/95) is to be ujsed in applying for these grants. Applications kits are available at most institutional offices of sponsored research and m