Carl Zeiss LSM 510 Confocal Inverted Microscope System

描述（由申请人提供）：此共享仪器赠款提案用于购买Carl Zeiss LSM 510共焦倒置显微镜系统。如果获得资助，这种最先进的共聚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中，并将由BIC成像设施的首席科学家Dennis McDaniel博士操作和维护。该仪器的操作将由主要研究者Chou-Zen Giam博士和BIC成像学院咨询委员会进一步指导，该委员会由Brian Schaefer博士（主席）、Michael Schell、Regina Armstrong和Sharon Juliano组成。McDaniel、Giam和Schaefer博士将与监督委员会协商，对仪器进行行政/科学监督。所有参与的研究人员都表示强烈需要拟议的显微镜，以支持他们各自的NIH资助的项目与复杂的成像应用，包括荧光恢复后光漂白（FRAP），固定和活细胞荧光共振能量转移（FRET），和高速多参数活细胞成像。BIC现有的PASCAL激光扫描共聚焦显微镜根本无法满足这些需求。LSM 510共聚焦显微镜的各种功能对于满足上述技术要求至关重要。该仪器支持的NIH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到NF-？B转录因子（Schaefer）;（4）癌细胞和脑细胞中的NADH成像，以及树突棘中肌动蛋白细胞骨架和IP 3代谢的调节（Schell）;（5）细胞质动力蛋白靶向微管+末端的机制（Xiang）;（6）癫痫发生中的谷氨酸受体（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致病机理&大肠杆菌细胞毒坏死因子。coli（奥布莱恩）。参与研究者（95%）将优先使用仪器，其余时间（5%）将按先到先得的原则分配给其他USU研究者。只有当仪器没有其他占用时，显微镜的使用才对校外研究人员开放。USU研究管理办公室已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。总的来说，卡尔蔡司LSM 510共聚焦倒置显微镜的收购是需要执行13个不同的NIH资助的项目，由5个不同的NIH研究所授予。因此，这一仪器要求对NIH的整体使命来说显然是重要的，即为改善公众健康的研究提供资金。

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.