Carl Zeiss LSM 510 Confocal Inverted Microscope System

描述(由申请人提供)：这份共享仪器赠款建议书用于购买卡尔·蔡司LSM 510共焦倒置显微镜系统。如果获得资金，这个最先进的共焦系统将被安置在统一服务大学(USU)生物医学仪器中心(BIC)的生物医学成像核心，并将由BIC成像设施的首席科学家Dennis McDaniel博士操作和维护。该仪器的操作将由首席研究员Chou-Zen Giam博士和由Brian Schaefer博士(主席)、Michael Schell博士、Regina Armstrong博士和Sharon Juliano博士组成的BIC成像学院咨询委员会进一步指导。McDaniel、Giam和Schaefer博士将与监督委员会协商，为该仪器提供行政/科学监督。所有参与的研究人员都表示，为了支持他们各自由NIH资助的具有复杂成像应用的项目，包括光漂白后荧光恢复(FRAP)、固定细胞和活细胞荧光共振能量转移(FRET)以及高速多参数活细胞成像，对拟议的显微镜有着强烈的需求。BIC现有的PASCAL激光扫描共聚焦显微镜根本不能满足这些需求。因此，所要求的LSM 510共聚焦显微镜的各种功能对于上述技术要求至关重要。该仪器将资助的研究项目包括：(1)HTLV-1的分子生物学和发病机制(GIAM)；(2)包膜病毒-宿主细胞相互作用(BRODER)；(3)T细胞受体(TCR)启动的细胞质信号转导至核因子-β转录因子(Schaefer)的分子机制；(4)癌细胞和脑细胞中NADH的成像，以及树突棘中肌动蛋白细胞骨架和IP3代谢的调节(Schell)；(5)细胞质动力蛋白靶向微管加端(XINA)的机制；(6)谷氨酸受体在癫痫发病中的作用(Bausch)；(7)血管紧张素II受体的二聚化(FENG)；(8)肠出血性大肠杆菌的发病机制和大肠杆菌的细胞毒性坏死性因子(O‘Brien)。该仪器将优先用于参与调查的调查员(95%)，其余时间(5%)将以先到先得的方式分配给其他USU内部调查员。只有在仪器未被占用的情况下，外部调查人员才能使用显微镜。美国苏黎世州立大学研究行政办公室承诺进一步升级该仪器，增加钛蓝宝石激光器，以实现参与研究人员目前和未来NIH资助的研究项目所需的各种多光子应用。总体而言，需要购买卡尔·蔡司LSM 510共焦倒置显微镜，以执行由5个不同的NIH研究所授予的13个不同的NIH资助项目。因此，这一仪器要求对美国国立卫生研究院的总体使命具有明显的重要性，即资助将改善公共卫生的研究。

DESCRIPTION (provided by applicant): This shared instrument grant proposal is for the purchase of a Carl Zeiss LSM 510 Confocal Inverted Microscope System. This state-of-the-art confocal system, if funded, will be housed in the Biomedical Imaging Core of the Uniformed Services University (USU) Biomedical Instrumentation Center (BIC) and will be operated and maintained by Dr. Dennis McDaniel, the Chief Scientist of the BIC Imaging Facility. Operation of this instrument will be further directed by the principal investigator, Dr. Chou-Zen Giam and the BIC Imaging Faculty Advisory Committee, comprised of Drs. Brian Schaefer (Chair), Michael Schell, Regina Armstrong and Sharon Juliano. Drs. McDaniel, Giam and Schaefer, in consultation with the supervisory committee, will provide the administrative/scientific oversight for the instrument. All participating investigators have indicated a strong need for the proposed microscope in order to support their respective NIH-funded projects with sophisticated imaging applications, including fluorescence recovery after photobleaching (FRAP), fixed- and live-cell fluorescence resonance energy transfer (FRET), and high-speed multi-parameter live cell imaging. The existing PASCAL laser scanning confocal microscope in the BIC simply cannot satisfy these needs. The various features of the requested LSM 510 confocal microscope are therefore critical for the aforementioned technical demands. NIH-funded research projects to be supported by this instrument include: (1) Molecular Biology and Pathogenesis of HTLV-1 (Giam); (2) Enveloped Virus-host Cell Interactions (Broder); (3) Molecular mechanisms of T cell receptor (TCR)-initiated cytoplasmic signal transduction to the NF-?B transcription factor (Schaefer); (4) Imaging NADH in cancer cells and in brain cells, and regulation of the actin cytoskeleton and IP3 metabolism in dendritic spines (Schell); (5) The mechanism of cytoplasmic dynein's targeting to the microtubule plus end (Xiang); (6) Glutamate receptors in epileptogenesis (Bausch); (7) Dimerization of the Angiotensin II Receptors (Feng); and (8) Pathogenesis of enterohemorrhagic Escherichia coli & cytotoxic necrotizing factor of E. coli (O'Brien). The priority for use of the instrument will be given to the participating investigators (95%) and the remaining time (5%) will be allotted to other intramural USU investigators on a first- come-first-served basis. The use of the microscope will be open to extramural investigators only when the instrument is not otherwise occupied. The USU Office of Research Administration has made a commitment to further upgrade this instrument with the addition of a Ti-Sapphire laser, to enable various multiphoton applications, needed for the present and future NIH funded research projects of the participating investigators. Overall, the acquisition of the Carl Zeiss LSM 510 Confocal Inverted Microscope is required for the execution of 13 different NIH funded projects awarded by 5 different NIH institutes. This instrumentation request is thus of obvious importance to the overall mission of the NIH, to fund research that will improve public health.