Full Text DA-95-001 NEUROSCIENCE NETWORKS IN BASIC DRUG ABUSE RESEARCH NIH GUIDE, Volume 24, Number 1, January 13, 1995 RFA: DA-95-001 P.T. 34 Keywords: Drugs/Drug Abuse Neuroscience National Institute on Drug Abuse Letter of Intent Receipt Date: March 16, 1995 Application Receipt Date: April 19, 1995 PURPOSE The National Institute on Drug Abuse (NIDA) invites applications to establish networks of investigators currently engaged in neuroscience research programs for the purpose of bringing relevant aspects of those programs to bear upon drug abuse research. Each network will be assembled by a Principal Investigator to form a multidisciplinary, multi-institutional consortium of neuroscience expertise centered upon a particular theme related to drug abuse research. These themes may be broad in scope, but should be concerned with identifying fundamental brain processes susceptible to the actions of drugs of abuse and the mechanisms through which drugs of abuse affect those processes. The intent of the request for applications (RFA) is to encourage cooperative efforts among network investigators to stimulate novel insights and innovative approaches to drug abuse research not presently achievable through collaborative efforts limited by geographical constraints. This RFA also is intended to extend existing research programs in the basic neurosciences into avenues directly relevant to drug abuse research with the goal of acquiring additional knowledge which ultimately may lead to new therapeutic and prevention strategies applicable to the public health problem of drug abuse. A minimum of three research projects must constitute the network, plus a core component concerned with establishing communication and information links among network members. In addition to stimulating substantive new research programs in drug abuse through this RFA, NIDA anticipates that the neuroscience networks created through this initiative will serve as experimental prototypes for new research enterprises devoted to studies on drug abuse within the environment of rapidly advancing communications and information technologies now revolutionizing contemporary biomedical research. 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, Neuroscience Networks in Basic Drug Abuse Research, is related to the priority areas of tobacco, alcohol and other drugs, maternal and infant health, and HIV infection. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for profit and non-profit, public and private organizations, e.g., colleges, universities, hospitals, laboratories, units of State and local government and their agencies, and eligible agencies of the Federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORT The mechanism of support will be the program project grant (P01). Studies involving collaborative efforts among investigators in all aspects of basic neuroscience relevant to drug abuse research are encouraged. The NIDA is employing the P01 mechanism initially for its Neuroscience Network initiative to determine the feasibility, synergy, and productivity of the Network concept. The total project period for applications submitted in response to this RFA may not exceed five years. During this period, network members may wish to submit individual R01 grants to more fully expand efforts started under this network initiative while continuing their participation within the network. FUNDS AVAILABLE The estimated total funds (direct and indirect) available for first year support for all awards under this RFA will be $2 million. Applications must not request budgets in excess of $1 million total costs in the first year. Because the nature and scope of the work proposed in response to this RFA may vary, the size and number of the awards will also vary. In Fiscal Year 1995, NIDA anticipates funding approximately two P01 awards. This number is dependent upon the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of NIDA, awards made pursuant to this RFA will be contingent upon the continued availability of funds for this purpose. The earliest feasible start date for the awards will be September 1995. RESEARCH OBJECTIVES Background A recurring theme in contemporary biomedical research is the existence of homologous molecules and mechanisms in diverse, but critical biological processes. In the explosive field of neuroscience, this theme has become particularly evident on a variety of fronts; for example, studies on the membrane protein, bacteriorhodopsin, have provided important insights into receptors for neurotransmitters and modulators that play a role in sensory perception, and that also may be involved in learning and memory, as well as attention and arousal. Other studies are revealing key roles for neurotransmitters, neuropeptides, and cytokines in linking interactions between neuronal and immune systems; and a compelling body of evidence now is accumulating that indicates that vital brain processes -- such as the activity driven plasticity through which developing synapses are refined and adult synapses are modified in learning and memory -- may share similar mechanisms and molecules. In drug abuse research as well, this theme has emerged in a particularly pronounced fashion as investigators have recognized two important facts: first, that the neuronal changes related to the accumulated effects of addiction -- including tolerance, dependence and sensitization -- represent drug induced neuronal plasticity governed by principles and mediated through processes consonant with those for other forms of neuronal adaptations; and, second, that understanding the interplay between genetic and environmental influences upon brain function is intimately involved with identifying brain sites and processes vulnerable to the actions of drugs of abuse, as well as the consequences of those actions on nervous system function and behavior. Today, myriad findings from drug abuse research have intriguing counterparts in other areas of neuroscience research. We know, for example, that systems involving adenylate cyclase and its related kinase (long-studied in a variety of processes, including simple models of learning and memory) are affected in the nerve cells of the locus ceruleus after chronic opioid administration. We know that morphine affects the phosphorylation state of cyclic AMP response element binding protein (CREB), a critical transcription factor studied in a host of biological phenomena. We know that long-term potentiation and long-term depression (extensively investigated as models of cellular adaptations in the hippocampus and cortex) also occur in the nucleus accumbens, an important brain site implicated in the "reward" processes associated with drug abuse. We know that nitric oxide, a novel neurotransmitter gaining great attention because of its diverse role in processes ranging from development to neurotransmitter secretion, also functions in the development of morphine tolerance. We know that certain neurotrophins -- well studied for their roles in development and regeneration -- attenuate some of the cellular effects of morphine, and may be affected in their expression by morphine. And we know that contemporary theoretical and experimental work focused on understanding rules governing how the brain anticipates learning also may be relevant to elucidating how reward and reinforcement influence learning. Examples such as these underscore the importance of leveraging limited research resources in ways that encourage and enable investigators to explore several biomedical consequences of their work. In particular, they illustrate the possibility that ongoing research programs in the basic neurosciences not presently addressing drug abuse may, indeed, also have direct relevance to revealing brain mechanisms associated with addiction; and they emphatically emphasize the need for creative research approaches that will stimulate such considerations. A second recurring theme in contemporary biomedical research is the growing importance of interdisciplinary collaborations. In drug abuse research, which by its nature has always relied upon a variety of scientific approaches (from the pharmacological to the behavioral sciences), this theme is gaining unprecedented importance. Indeed, the field of drug abuse research now may be among the most rapid embracing interdisciplinary approaches, for accessible to it are animal models that permit prominent features of drug addiction to be studied in the laboratory -- a tool not elsewhere available to many neuroscientists. This advantage facilitates extensive studies at the molecular and cellular level, opening the way for achieving detailed biological insights into complex and clinically important behaviors. With the recent cloning of genes for the receptors of every major drug of abuse, and the possibility of temporally controlled, tissue specific gene manipulations waiting upon the horizon, the stage now is set for moving the field of drug abuse research beyond cloning, to sophisticated, mechanistic investigations exploring relationships among protein function and regulation, brain structure and function, and behavior, and how drugs of abuse affect these relationships. Clearly, however, such explorations will require new and creative approaches integrating expertise and perspectives from all aspects of the basic neurosciences. Now, more than ever, it is critical that behavioral scientists recognize the opportunities and limitations of molecular neurobiology, and that molecular neurobiologists develop appropriate behavioral assays to assess the consequences of their molecular manipulations. Similarly, it is vital that clinicians, imaging scientists, psychologists, and others collaborate to design safe, appropriate, informative, and reliable experiments when investigating fundamental aspects of human brain function; and that those engaged in human studies interact effectively with those involved in animal studies to achieve appropriate interpretations of results across species. A third theme emerging from contemporary biomedical research is the growing importance of communication and information technologies. The advent of high performance computing research already has greatly advanced many areas of investigation, such as structural biology, neuroscience, and cell biology. Even greater opportunities appear to exist as information and communication technologies become increasingly integrated. Today, desktop conferencing systems include software enabling multiple users to work on a variety of applications, including text, graphics, images and data, while seeing and talking to each other. Additionally, prototype projects already have demonstrated the feasibility of accessing and operating costly equipment, such as higher voltage electron microscopes, at remote sites. Elsewhere, new software applications are providing opportunities to utilize simulations for safer, less costly means of gaining experience in performing biological procedures and for investigating biological mechanisms. These, and other developments signal the evolving structure of contemporary research communities: a structure rapidly becoming as dependent upon information and telecommunication links, as it is upon traditional laboratory configurations. As drug abuse research relies increasingly upon the creativity and strength of multidisciplinary approaches and the power of new technologies to move its research programs more vigorously into the basic neurosciences, it is critical that NIDA develop experimental prototypes for new research enterprises responsive to the evolving nature of biomedical research communities. In particular, NIDA recognizes the importance of contemplating and initiating the creation of thematic, electronically linked "virtual research centers" to complement its traditional centers program, which heavily relies upon geographical contiguity. Research Scope This initiative has three principal objectives: (1) to stimulate novel insights and innovative approaches in drug abuse research through the establishment of national, collaborative networks of investigators active in the neurosciences; (2) to encourage and enable neuroscientists not currently focused on drug abuse research to explore applications of their expertise to the field; and (3) to develop experimental prototypes of research enterprises that exploit emerging communication and information technologies to form "virtual research centers" in the drug abuse field. Scope of the Neuroscience Research Component The first two objectives focus on increasing understanding of basic neural processes susceptible to the actions of drugs of abuse, and how drugs of abuse affect those processes. To accomplish these objectives, a Principal Investigator is invited to submit an application proposing a multi-institutional, multidisciplinary consortium (i.e., a network) of collaborators presently engaged in established research programs in the neurosciences, for the purpose of focusing the network's expertise upon a particular scientific theme relevant to drug abuse research. NIDA especially encourages applications that develop a theme based on the concept of drug abuse as a model system for investigating all aspects of neurobiological mechanisms associated with plasticity, and particularly the role of use-dependent synaptic modifications in understanding behaviors and brain mechanisms related to drug abuse and the actions of drugs. Network themes may focus upon a series of studies aimed at elucidating the interplay of mechanisms at the cellular level, or they may choose to focus on a multilevel approach, exploring brain function and drug action from the systems level to a molecular one. Themes may focus on a particular central nervous system function implicated in drug abuse, or on mechanistic studies associated with a particular drug of abuse. Themes focused on particular drugs of abuse should clearly articulate any broad principles regarding neuronal function and drug abuse that may derive from studies on specific drugs or related compounds. Studies may also explore interactions among the nervous system and other physiological systems, such as neuroendocrine and neuroimmune systems, in efforts to elucidate the causes and consequences of drug seeking behavior and mechanisms of drug actions. (In those cases where a network theme or project also may have relevance to AIDS-related research, applicants are strongly encouraged to discuss this relevance explicitly in the background section of their application.) Investigators are encouraged to recognize that a network's theme may be broad in scope, and creativity and originality are encouraged in identifying and developing a research theme. Examples of possible network themes include, but are not limited to, the following: o the neural basis of drug abuse, from molecules to behavior; o the neurobiology of motivation in understanding drug seeking behaviors; o the role of post-transcriptional processes in drug-related neuronal adaptations; o drug regulation of protein turnover, including protein processing, targeting, trafficking, and regulation; o drug abuse and the neurobiology of brain development; o the role of certain endogenous systems (such as the opioid, cannabinoid, and nicotinic systems) in normal CNS function, and how drugs of abuse perturb those roles; o mechanisms of neuronal adaptations in critical brain regions affected by drugs of abuse, such as the nucleus accumbens; o explorations of relationships between drug induced brain "rewards" and learning and memory; o the effects of drugs of abuse on neuroimmune and neuroendocrine function; o the role of novel neurotransmitters in drug-induced neuronal plasticity; o the function of endogenous systems (such as the opioids) in neuromodulatory mechanisms, and the effects of drugs of abuse upon those systems. o investigations into pre- and post-synaptic mechanisms by which drugs of abuse alter synaptic efficacy. Network applications must consist of at least three interactive and interdependent projects conducted at independent laboratory sites and a communication core. Network members should be engaged in an active neuroscience research program, which, although not directly centered on drug abuse, has potential relevance to drug abuse research; however, the Principal Investigator may designate one network component as an "Exploratory Project." This project need not be based on an active, ongoing program or extensive preliminary data. It should represent a highly innovative study for which the potential significant scientific contribution offsets potential concerns about project feasibility. Funds for an "Exploratory Project" may be applied to testing the feasibility of an approach, gathering additional data, or conducting other activities that demonstrate the project's significance. Applicants should note that the initiative described in this RFA is not to be construed as a means for merely assembling and supplementing existing, ongoing programs in drug abuse research. This initiative is intended to provide limited funds to encourage and enable applications of basic neuroscience projects to drug abuse research. Investigators currently engaged in drug abuse research may be network members, but network projects for such investigators should represent novel avenues of study that would benefit greatly from network participation and/or contribute greatly to a network's theme. Conversely, this initiative is not intended to merely supplement existing research programs in the basic neurosciences. Network applications must clearly articulate a coherent theme relevant to drug abuse research, and explicitly and carefully describe the potential relevance of each network component to drug abuse research, the scientific interactions anticipated among network members, and the expected benefits to be derived to drug abuse research from the network approach. Communication Core To achieve the third objectives of this RFA, applications must include plans for a Communication Core. Principal Investigators may request support for equipment and personnel necessary to achieve the communications and interactions essential to the Network's theme and activities. An important aspect of this core will be to exploit emerging communication and information technologies among geographically dispersed communities of investigators. Issues to consider in the communications core may include, but are not limited to, the following: o Diversity and compatibility among communications and information hardware and software available to Network laboratories; o "Real time" versus other modes of communications, such as Email and bulletin boards; o Mechanisms and procedures for safeguarding and sharing information, generating new information from shared information resources, and crediting investigators' work when information is obtained or generated from shared resources. Although data development and sharing may be an important and integral activity of a Network's communication core, this RFA is not intended to provide a means for largely establishing and manipulating extensive neuroscience data bases. This RFA is focused on hypothesis driven projects that may involve data sharing. Applications focused principally on data base development and informatics should consider submitting applications under the Human Brain Project (HBP) Initiative. For additional information about the HBP initiative, investigators are encouraged to contact the program representative listed under INQUIRIES. SPECIAL REQUIREMENTS Advisory Panel Because network members may be either newcomers to the field of drug abuse research, or investigators established in one aspect of drug abuse research (but not necessarily another), applications should include plans for utilizing an Advisory Panel to assist the network in periodic evaluation of its program. The Advisory Panel should be composed of at least three investigators, two of whom should be well respected for their expertise in the field of drug abuse research. These plans should explicitly delineate the nature and extent of interactions with Advisory Panel members and should include at least one annual meeting between network and Advisory Panel members. The Principal Investigator may also schedule additional meetings at network sites, if appropriate. Principal Investigators are requested to notify the NIDA program official responsible for the network grant at least 45 days prior to any scheduled meetings, so that the official may have the opportunity to attend. Applications should specifically identify Advisory Panel members, their areas of expertise, and the relevance of that expertise to accomplishing the research goals related to the network's theme. Letters of collaboration from Advisory Panel members must be included with the application. Composition of Network To encourage collaborations and diversity in perspectives among laboratories, networks may not contain more than two component projects from a single institution or campus or other non-academic organization eligible under this RFA. Director Each Network will have a Director responsible for organizing, administering, and directing the Network's activities. The Director must commit at least 20 percent effort to the grant and be Principal Investigator of one of the projects. Progress Reports Annual progress reports accompanying noncompeting continuation applications should specifically address the nature of Network interactions, including opportunities and problems associated with those interactions, and proposed solutions for addressing any identified problems. This discussion should be useful to NIDA for evaluating the feasibility of potential future Network initiatives. Principal investigators and subproject leaders in the Network will be requested to voluntarily submit manuscripts accepted for publication to the Network's NIDA program administrator at least two weeks prior to publication, so that a current summary of program accomplishments may be maintained during the funding period of the grant. 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 494B 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 may also obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. 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 GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or principal investigator could be included with the application. LETTER OF INTENT Prospective applicants are asked to submit, by March 16, 1995, 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 this RFA. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains allows NIDA staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent (or faxed) to: Eleanor Friedenberg Office of Extramural Program Review National Institute on Drug Abuse 5600 Fishers Lane, Room 10-42 Rockville, MD 20857 FAX: (301) 443-0538 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research; from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 710-0267. The RFA label available in the application form PHS 398 (rev. 9/91) must be affixed to the bottom of the original face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2a on the face page of the application form and the YES box must be marked. Submit a signed, typewritten original of the application, including the Checklist, and three signed photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies of the application must be sent to: Director of Office of Extramural Program Review National Institute on Drug Abuse 5600 Fishers Lane, Room 10-42 Rockville, MD 20857 Applications must be received by April 19, 1995. 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 for completeness by DRG and responsiveness by the NIDA. Incomplete applications or applications that are not responsive will be returned to the applicant without further consideration. Applications that are complete and responsive to this RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIDA in accordance with the review criteria stated below. As part of the initial merit review, triage will be used by the initial review group in which applications will be determined to be competitive or noncompetitive, based on their scientific merit relative to other applications received in response to this RFA. Applications judged to be competitive will be discussed and assigned a priority score. Applications determined to be noncompetitive will be withdrawn from further consideration and the Principal Investigator and the official signing for the applicant organization will be notified. Review Criteria The IRG review of scientific and technical merit of the Program Project grant application will emphasize two major aspects: (1) review of the program as an integrated research effort focused on a central theme, and (2) the review of each component project and core unit(s). The review will also include an assessment of the academic climate and physical environment and special considerations, e.g., compliance with the human subjects and animal welfare regulations. The IRG will assign a priority score for the entire program rather that for each individual project recommended for further consideration. The assessment of the scientific and technical merit will include the following: Program as an Integrated Effort o The significance of the overall program goals and the development of a well-defined central research focus of importance and relevant to the goals of this RFA. o The multidisciplinary or multifaceted character of the program, i.e., the coordination, cohesiveness, interrelationship, and synergistic potential among the individual projects and core(s). o The justification for, and usefulness of the core facilities to the research projects. Each core unit must provide essential facilities or services for two or more approved individual projects. For the communication core, the feasibility of proposed approaches for using information and communication technologies in establishing networks of neuroscientists focused on scientific aspects of drug abuse research. o Administrative arrangements and/or organizational structure, through an administrative and/or communication core, to facilitate and monitor the attainment of objectives and quality control. For example, these factors will include plans to enhance communication and cooperation among the investigators involved in the program and utilization of the advisory panel mechanism to assist the network in advancing its progress. o The scientific leadership, ability, stature, experience, and administrative competence of the Program Director and his or her commitment and ability to devote substantial time and at least 20 percent effort to the program. o The scientific stature of the Principal Investigators and the extent to which each contributes to the overall program goals as well as their commitment to the program. o Accomplishments and progress of the program to date, if appropriate. o Reasonableness of the overall budget for the proposed work. Individual Projects and Core Units o The scientific and technical merit of each research project and core unit. o The accomplishments and progress for the projects and the core units to date for ongoing projects. o The qualifications, experience, and commitment of the investigators responsible for the research projects or core units, including their ability to devote adequate time and effort to the project. o For any component designated as an "Exploratory Project," the potential for significant scientific contribution, the uniqueness of the scientific approach, and the qualifications of the investigator. o The appropriateness of the budget for each of the proposed projects and core units. Resources and Environment o The academic climate and physical environment in which the research will be conducted, including the availability of space, equipment, research subjects, etc., and the potential for interaction with scientists from other departments and/or institutions in addition to network members. o Institutional strength, stability and commitment to research and support for the proposed program, including fiscal responsibility and management capability to assist the Program Director and staff in following DHHS, PHS, and NIH policies. Other Considerations o When an application involves potential adverse effects on humans or animals, adequacy of the proposed means for protecting against such effects must be demonstrated. 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. AWARD CRITERIA The anticipated date of award is September 1995. In making awards, the scientific/technical merit of applications, availability of funds, and program balance among research areas will be considered. INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding program issues to Karen J. Skinner, Ph.D. Division of Basic Research National Institute on Drug Abuse 5600 Fishers Lane, Room 10A-19 Rockville, MD 20857 Telephone: (301) 443-1887 FAX: (301) 594-6043 Email: kskinner@aoada.ssw.dhhs.gov Direct inquiries regarding fiscal matters to: Gary Fleming, J.D., M.A. Grants Management Branch National Institute on Drug Abuse 5600 Fishers Lane, Room 8A-54 Rockville, MD 20857 Telephone: (301) 443-6710 FAX: (301) 594-6847 Email: gfleming@aoada.ssw.dhhs.gov AUTHORITY AND REGULATIONS This program is described in the Catalogue of Federal Domestic Assistance No. 93.279. 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 of Health Systems Agency review. The Public Health Service strongly encourages all grant recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. .
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