ADMINISTRATIVE CORE

行政核心

• 批准号: 7287653
• 负责人: Paul R Vezina
• 金额: $ 6.81万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7287653
• 关键词: Accountability; Administrative Personnel; Advertising; Advisory Committees; Affect; Anatomy; Animals; Annual Reports; Antibodies; Applications Grants; Area; Behavior; Behavioral; Binding; Binding Proteins; Biochemical; Biological; Biology; Biomedical Research; Brain; Brain region; California; Canada; Characteristics; Chicago; Cities; Commit; Committee Members; Communities; Condition; Consult; Contracts; Cultured Cells; Data; Data Reporting; Date/Time; Decision Making; Dependence; Disease; Doctor of Philosophy; Dose; Drosophila acetylcholine receptor alpha-subunit; Drug abuse; Electrophysiology (science); Ensure; Expenditure; Experimental Designs; Exposure to; Faculty; Feedback; Fostering; Future; Goals; Grant; Growth; Guidelines; Human Resources; Immunoprecipitation; In Vitro; Individual; Injection of therapeutic agent; Institutes; Institution; International; Investigation; Joints; Journals; Knowledge; Letters; Light; Link; Logistics; Maps; Maryland; Mecamylamine; Medical Genetics; Methods; Minnesota; Modeling; Molecular; Monitor; National Institute of Drug Abuse; Neurobiology; Neurons; Neurosciences; Nicotine; Nicotine Dependence; Nicotinic Receptors; Office of Administrative Management; Oral; Outcomes Research; Participant; Performance; Personal Satisfaction; Pharmacology; Post-Translational Protein Processing; Postdoctoral Fellow; Preparation; Principal Investigator; Process; Program Research Project Grants; Program Reviews; Progress Reports; Protocols documentation; Psychiatry; Publishing; Rattus; Recommendation; Regulation; Relative (related person); Reporting; Research; Research Activity; Research Personnel; Research Project Grants; Resources; Role; Running; Schedule; Scientist; Self Administration; Signal Transduction Pathway; Site; Slice; Solutions; Standards of Weights and Measures; Students; Suggestion; System; Techniques; Technology; Telefacsimile; Testing; Time; Tissue Banks; Tissue Sample; Tissues; To specify; Tobacco; Tobacco Dependence; Training; Training Activity; Training Programs; Travel; Treatment Protocols; Twin Multiple Birth; United States National Institutes of Health; Universities; Up-Regulation; Update; Utah; Validation; Vendor; Visit; Wages; Withdrawal; Work; Writing; animal tissue; base; behavioral pharmacology; behavioral sensitization; brain tissue; day; dissemination research; experience; in vivo; interdisciplinary approach; interest; medical schools; member; multidisciplinary; neurochemistry; neuronal excitability; professor; programs; receptor; receptor upregulation; research study; symposium; therapy development; tissue preparation; tool; tool development; trafficking; willingness

by investigators in Project 2. Brain tissues obtained from rats subjected to behavioral and biochemical tests in Project 3 will be analyzed in Projects 1 and 2. Project 2 will provide the Core with rats for nicotine exposure using protocols established in Project 3. Brain tissue samples from these rats will then be made available for examination in Project 2 (see Figure 2 below). As Tissue Bank Coordinator, Mr. Scott-Railton will subject rats to the required nicotine exposure regimens and ensure that they or appropriate tissues are forwarded to the proper experiments. He will also document these activities, supervise their execution by personnel from the different Projects, and provide training as necessary. Depending on the preparation, tissue extraction will be performed by personnel assigned by the different Projects. In his capacity as Tissue Bank Coordinator, Mr. Scott-Railton will ensure both compliance to specified experimental designs and correspondence between experiments conducted in the three projects. He is well versed in the necessary techniques. In addition to his role as Tissue Bank Coordinator, Mr. Scott-Railton will devote the remainder of his effort to conducting experiments in Project 3. The Tissue Bank Coordinator will report directly to Dr. Vezina. - Administrative Assistant: Laura Lindley. This experienced individual, already working as Administrative Assistant for the NIDA Training Program, will - schedule all meetings and handle the logistics for the annual meeting with the External Advisory Committee - order supplies - ensure administrative processing of newly appointed personnel - provide administrative support for all personnel on the Program Project - track, manage and report expenditures on the Program Project to the Core and Project Leaders - help the Core Leader complete and submit both competing and non-competing renewal applications - assist the Core Leader track and compile experimental results produced by the different Projects PHS 398/2590 (Rev.09/04, Reissued 4/2006} Page 18 Continuation Format Page Principal Investigator/Program Director (Last. First, Middle): VEZINA, Paul - assist the Core Leader draft and assemble the Annual Report and ensure that it is distributed to members of the External Advisory Committee in timely manner before the annual meeting. Ms. Lindley will devote her remaining effort to duties as Administrative Assistant to the NIDA Training Program, which will provide the corresponding salary support. In both cases, Ms. Lindley will report directly to Dr. Vezina and thus facilitate the joint management of the Program Project and the NIDA Training Program and, importantly, help cultivate interactions between the two. C.2. Animal Preparation and Tissue Sharing The experiments proposed in this Program Project will use a multidisciplinary approach to study the impact of exposure to nicotine on nicotinic acetylcholine receptors (nAChRs), neuronal excitability and behavior. Central to this approach will be the seamless flow and sharing of animals and tissues between the different Projects. In Project 1, for example, cultured cells will be examined at a molecular biological level and subjected to further electrophysiological analyses with help and training provided by investigators in Project 2. Brain tissues obtained from rats subjected to behavioral and biochemical tests in Project 3 will be analyzed in Projects 1 and 2. Project 2 will provide the Core with rats for nicotine exposure using protocols established in Project 3. Brain Figure 2. Function of the Administrative Core in the preparation of rats and the flow of tissues between the different Projects. Arrows highlight the flow of animals and tissues between Projects via the Core. "¿*¿ the electrophysiological analysis of cultured cells from Project 1 will be assisted by access to expertise in Project 2, """^ rats from Project 2 will be prepared by the Core and returned to it for slice electrophysiology, "^ tissues from rats tested in Project 3 will be made available for analyses in Projects 1 and 2. tissue samples from these rats will then be made available for electrophysiological examination in Project 2 (see Figure 2). A critical function of the Administrative Core will thus be to coordinate, document and oversee the preparation and sharing of tissue samples between the three Projects. The Administrative Core will be responsible for exposing rats to various nicotine regimens and ensuring that they or appropriate tissues are forwarded to the proper experiments. Compliance to specified experimental designs and procedural and experimental correspondence between experiments conducted in the different Projects will thus be ensured. As outlined above, John Scott-Railton, the Tissue Bank Coordinator, will be responsible for, contribute to and oversee these activities. C. 3. Monthly Investigator Meetings Given the multidisciplinary and multi-group approach of this Program Project, it will be critical to have mechanisms in place that ensure the timely and regular integration of information, ideas, and results produced in the three different Projects. The Administrative Core will fill this need by arranging for the Project Leaders and their associated research teams to meet on a monthly basis at a scheduled date and time. Dr. Paul Vezina, Principal Investigator of the Program Project and Core Leader, will chair these meetings. The agenda for these regular meetings will include the up-to-date reporting of data collected and discussion of issues related to the smooth running of the Program Project, such as animal utilization, tissue sharing, problems encountered and, if necessary, potential solutions. The group will critically review scientific findings obtained as well as administrative and financial matters that affect the Program as a whole. All members of the different PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page 19 Continuation Format Page Principal Investigator/Program Director (Last, First, Middle): VEZINA, Paul research teams will participate in these meetings. Students and postdoctoral fellows, in particular, will be encouraged to contribute, especially in the form of data presentations and seminars that strive to integrate findings from the different Projects. These meetings will ensure that the integration of the research activities of individual Projects is maintained within the context of the overall Program Project and will help the Principal Investigator, Dr. Vezina, determine appropriate courses of action to this end. The regular review and analysis of research findings will help the Core and Project Leaders regularly assess their working hypotheses, revise these hypotheses if necessary, and possibly redirect resources available to the Program. Most importantly, the monthly investigator meetings will not only allow investigators in the different Projects to obtain feedback on their own findings but will encourage them to compare their findings and apply them together to the overall working model of the Program Project. As illustrated in Figure 3, information obtained in Project 1 on nAChR Receptor upregulation and subtype Functional receptor upregulation; LTP Brain region; injection regimen; behavioral and biochemical sensitization Integration Figure 3. Information flow between the Administrative Core and Project components of the Program Project. While ideas and results already flow and will continue to be exchanged between the different Projects, the Administrative Core will function as a center for the regular and timely integration of this information. This function is vital to the decision-making processes that impact the scientific direction of each Project relative to each other as well as of the Program Project as a whole. upregulation and subtype will inform the other two projects on the time course of receptor regulation and which receptor subtypes to target in current and future experiments. Similarly, information obtained in Project 2 on the functional upregulation of nAChRs and LTP will be compared to the findings obtained in Project 1 and inform it and Project 3 on the time course of the functional receptor regulation and LTP observed and the neuronal systems involved. Finally, information obtained in Project 3 will inform the other two Projects on which regimens of nicotine injections produce behavioral and biochemical sensitization, which brain regions are involved, and the time course of the sensitization produced by the different regimens. This approach will facilitate the study of the effect of nicotine exposure on behavior simultaneously at molecular, cellular, behavioral and biochemical levels of analysis. Thus, the monthly investigator meetings will foster the comparison of findings obtained using different approaches in the different Projects and their integration into a unified model. None of the individual Projects alone could achieve this multidisciplinary level of analysis and the building and progressive assessment of such an integrated model of the effects of exposure to nicotine. Indeed, as illustrated in Figure 4, this Program Project proposes the ongoing detailed exchange of ideas between Program Project components that is necessary for such an approach to succeed. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page 20 Continuation Format Page Principal Investigator/Program Director (Last, First, Middle): P1.1. Characterize pharmacology and upregulation of a3, a4, & a6 containing nAChRs in vitro - assess subunit-specific antibodies, functional upregulation, onset, decay, nicotine dose-dependence of upregulation P1.2. Characterize mechanisms underlying nAChR upregulation - receptor assembly/trafficking - post-translational modifications - signal transduction pathways - chimeric exchange P1.3. Characterize nAChR upregulation produced in vivo by different nicotine exposure regimens, using subtype specific binding, protein analyses and immunoprecipitation with subunit specific antibodies VEZINA, Paul P2.1-3 - will exploit evolving tools to extend investigation of functional upregulation of nAChRs in vivo - will correlate characteristics of nAChR upregulation to those obtained in vivo P3.2 - will evaluate rank order potency of different pharmacological tools in vivo as these become available to assess nAChR subunit composition Future Directions: Long-term goal of Program Project is to directly modulate upregulation of particular nAChRs to establish causal relationships between receptor upregulation (P1.2) and P2.1-3 functional nAChR upregulation and LTP P3.1-3 biochemical and behavioral sensitization P2.1-3 - will correlate findings with those obtained in VTA and LTD for functional nAChR upregulation and LTP - will use findings to direct further testing (exposure regimen, withdrawal time, brain area) P3.1&3 - will correlate findings with those obtained for biochemical and behavioral sensitization P2.1. Assess functional nAChR upregulation produced in the VTA and LOT by different nicotine exposure regimens in vivo P2.2. Assess induction of LTP produced in VTA by different nicotine exposure regimens in vivo P2.3. Assess induction of LTP produced in LDT by different nicotine exposure regimens in vivo P3.1. Characterize effect of different nicotine exposure regimens (light to intense) on induction and expression of locomotor and biochemical sensitization at different withdrawal times P3.2. Map, with mecamylamine, nAChR fields in brain necessary for nicotine sensitization P3.3. Determine effect of sensitization to nicotine on nicotine self-administration P1.1&3 - will correlate findings with binding data at different withdrawal times - will use findings to fine tune further nAChR characterization and development of tools P3.1&3 - will correlate findings with those obtained for biochemical and behavioral sensitization at different withdrawal times P1.1&3 - will correlate findings with binding data at different withdrawal times - will use findings to fine tune further nAChR characterization and development of tools P3.1&3 - will correlate findings with those obtained for biochemical and behavioral sensitization at different withdrawal times P1.1&3 - will correlate findings with binding data at different withdrawal times - will use findings to fine tune further nAChR characterization and development of tools P3.1&3 - will correlate findings with those obtained for biochemical and behavioral sensitization at different withdrawal times P1.3 - will correlate findings with binding data at different withdrawal times P2.1-3 - will correlate findings with functional nAChR upregulation and LTP observed in vivo at different withdrawal times - will use findings to direct further conditions to test (exposure regimen, withdrawal time) P1.3 - will compare findings to binding data to assess link between nAChR upregulation and sensitization P2.1-3 - will compare findings to functional upregulation and LTP data obtained in VTA and LDT to assess link between nAChR upregulation, LTP and sensitization - will use findings to target other brain sites for analysis P1.3 - will compare findings to binding data to assess link between nAChR upregulation and sensitization of nicotine self-administration P2.1-3 - will compare findings to functional upregulation and LTP data obtained in VTA and LDT to assess link between nAChR upregulation, LTP and sensitization of nicotine self-administration Figure 4. Detailed outline of interactions between Program Project components. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page 21 Continuation Format Page Principal Investigator/Program Director (Last, First, Middle): VEZINA, Paul At these meetings, investigators will also discuss their upcoming animal needs with the Tissue Bank Coordinator and coordinate experiments to be conducted in the different Projects. Prior to these meetings, the Administrative Assistant will consult the Project Leaders to obtain any information that requires distribution to the other group members. C.4. Annual Meetings with the External Scientific Advisory Committee Although considerable expertise is already in place to successfully undertake the research described in this Program Project, the Project Leaders recognize the collective need and certain benefit to the Program of obtaining guidance and advice from a group of external experts. The help of four individuals with well- established reputations and recognized multidisciplinary expertise in the area of nicotine research was solicited. These four distinguished nicotine investigators, - Dr. William A. Corrigall, Professor of Psychiatry, University of Minnesota - Dr. Henry A. Lester, Professor of Biology, California Institute of Technology - Dr. Scott W. Rogers, Professor of Neurobiology and Anatomy, University of Utah - Dr. Derek van der Kooy, Professor of Molecular and Medical Genetics, University of Toronto, Canada have agreed to serve as members of an External Scientific Advisory Committee. The responsibility of this Committee will be to meet once a year on The University of Chicago campus with the Principal Investigator and the Project Leaders to review the progress, performance and activities of the Program Project and to make recommendations for improvement if necessary. During the one-day visit, progress during the preceding year and plans for the upcoming year will be formally reviewed. Program staff from NIH will also be welcome to attend. Dr. Vezina, Principal Investigator of the Program Project, will chair these formal review meetings with the External Advisory Committee and,in preparation for each, will draft an Annual Report. This Report will consist of updated progress reports from the Project Leaders, a discussion of the strengths and weaknesses associated with the different components of the Program Project, and plans for the next year. At the meeting, each of the three Project Leaders will give an oral presentation describing the progress made toward completing the specific aims of their respective Projects. In addition, Dr. Vezina, as Leader of the Administrative Core, will report on Core activities and grant finances. The Advisory Committee will then prepare its own written report and submit it to the Principal Investigator of the Program Project. Dr. Vezina will review this report and distribute it to the Project Leaders for discussion, consideration and implementation of recommendations at the next scheduled monthly investigator meeting. External Advisory Committee members will review the scientific progress of the three projects and, if necessary, will make suggestions regarding the redistribution and refocusing of project resources. A key task will be to ensure that individual Projects remain properly aligned and focused in the context of the overall Program Project and that experimental plans for each Project remain appropriate and do not become overly ambitious. In addition, to make the most of the scientific expertise of the External Advisory Committee and its presence on campus each year, one member of the Committee (Dr. Lester in year one) will present a seminar. These seminars will be scheduled for the late afternoon, after the review meeting in the morning. Following the talk, an informal reception will be held allowing time for students, postdoctoral fellows and faculty to interact with the speaker and the remaining Advisory Committee members. Recognizing the need and importance of creating new educational and training opportunities for local pre- and postdoctoral trainees and of promoting further growth in drug abuse related research at The University of Chicago and the greater Chicago neuroscience community, these seminars and receptions will be organized with the NIDA Training Program at The University of Chicago and will be advertised to faculty and staff on campus as well as neighboring institutions. Graduate students and postdoctoral fellows will be strongly encouraged to attend. Letters from these distinguished scientists indicating their willingness to serve on the External Scientific Advisory Committee are included with their biosketches following this Administrative Core Plan. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page 22 Continuation Format Page Principal Investigator/Program Director (Last, First, Middle): VEZINA, Paul C.5. Fiscal and Grant Management Plan The Administrative Core will be responsible for overseeing and ensuring day-to-day and fiscal management of the Program Project. The Core will maintain a management plan for fiscal and administrative accountability. In particular, the Administrative Assistant will generate monthly fiscal reports for the Core Leader and will provide administrative support for all personnel in the Program. Day-to-day fiscal and administrative management activities for which the Administrative Assistant will be responsible include: interacting with vendors; ensuring the legality of expenditures; managing purchasing, travel and other expenses; processing reimbursement documents; administering and monitoring subcontracts and consults; and ensuring administrative support for all personnel and administrative processing for new staff. Core staff will also track deadlines for continuation grant applications, annual reports, and final reports. C.6. Data Sharing Plan The University of Chicago is committed to the open and timely dissemination of research outcomes. Investigators in the proposed activity recognize that promising new methods and strategies may arise during the course of their research. They are aware of and agree to abide by the principles for sharing research resources as described by the NIH in "Principles and Guidelines for Recipients of NIH Research grants and Contracts on Obtaining and Disseminating Biomedical Research Resources." The Administrative Core provides for fully effective data sharing between Program Project participants through the establishment and scheduling of the monthly investigator meetings described above. Because all participants are faculty members, students, postdoctoral fellows and staff at The University of Chicago, this task is greatly simplified. Per standard practice, investigators will be expected to publish research results in high quality journals and present their findings at national and international conferences. The goal will be to provide data sharing in a way that expedites scientific discovery. D. UTILIZATION OF CORE BY INDIVIDUAL PROJECTS Each Project will use the Administrative Core equally. PHS 398/2590 (Rev.09/04, Reissued 4/2006) Page 23 Continuation Format Page UNIVERSITY OFMINNESOTA Twin Cities Campus Tobacco UseResearch Center Medical School May 11,2006 Paul Vezina, PhD Associate Professor Department of Psychiatry The University of Chicago 5841 South Maryland Avenue, MC 3077 Chicago, IL 60637 RE: University of Chicago Program Project Grant on Nicotine Exposure - External Scientific Advisory Committee Dear Paul, Suite 201 2701 University Avenue, S.E. Minneapolis, MN55414 Office: 612-627-1857 Fax: [phone] [e-mail] Thank you for your invitation to serve as a member of the External Advisory Committee for your Program Project Grant on "Nicotine exposure: Molecular to behavioral consequences" at The University of Chicago. I believe that it is through multidisciplinary approaches, such as this one proposed by you and your colleagues, that we will advance our knowledge of nicotine addiction in ways that in future will be valuable in the development of treatment tools. Hence I am pleased to accept your invitation, and am prepared to help in areas of my expertise, including the behavioral pharmacology of nicotine and the neurochemical and anatomical substrates for addictive disorders. Your research is actually in keeping with my interests in broadening target discovery and validation in tobacco addiction. As a member of the External Advisory Committee, I understand that I am expected to participate on-