MORPHOLOGY AND CELL IMAGING CORE

形态学和细胞成像核心一直在提供专业知识，技术支持， 协助形态学和成像方法以及最先进的设备， 先进的成像技术，以DDRCC成员超过18年的领导下，博士。 斯特尼尼核心小组提供的服务有助于开展研究，阐明 组织和细胞分布的信号分子，发挥作用，在控制胃肠道 (Gl)功能和在GI疾病的发病机制中的作用，以及用于可视化信号通路， 调节细胞功能。从核心中受益的研究已经使重要的 我们对神经元和激素通路之间的功能相互作用的理解的进展 调节GI功能，并导致许多出版物和长期合作。 这些年来，为了反映需求， 以及形态学和成像技术的发展，其目标是 增强核心能力。形态学能力的增强包括：1） 增加小鼠病理学服务和2）成立中央银行， 特征抗体。小鼠病理学服务已被添加到我们以前的竞争 更新，以满足许多CURE：DDRCC研究人员对专业知识和 帮助定义可以在遗传学上检测到的表型异常或病理， 操纵的小鼠，这是越来越多地使用在治愈：DDRCC。诺拉·罗森古特医生，一位经验丰富的 兽医病理学家，在自然和实验诱导的小鼠病理学方面具有丰富的专业知识 我一直担任核心副主任，监督这项服务，这已被广泛使用 在过去的融资周期中。添加了抗体中央银行，以提供集中的 在之前的资助期间，CURE生产了大量抗体 以及许多研究人员用作特定细胞类型标记的其他抗体， 细胞内信号分子。一个集中的银行的可用性， CURE感兴趣的经验证抗体：DDRCC研究人员是一个强大的资源， CURE的有效访问：DDRCC研究人员可以通过 形态学和细胞成像核心。Gordon Ohning博士将作为副主任加入核心， 负责维护中央抗体库。 我们的影像服务能力已大幅提升，包括： 增加了高度复杂的设备，2）采用了新的成像技术， 将进一步提高我们在细胞和亚细胞水平上观察分子的能力， 在细胞激活后的第二信使系统中。我们的成像技术的一个主要丰富 设施已经增加了一个国家的最先进的共聚焦显微镜，蔡司LSM 510 Meta 配备先进的软件（例如解卷积、图像分析、3D渲染）， 活细胞和固定细胞成像。该系统是在机构资金的帮助下获得的 大卫格芬加州大学洛杉矶分校医学院就在之前的竞争性更新，从那时起，它 已被越来越多的CURE：DDRCC研究者大量使用。在过去 在一个受资助的周期中，我们还通过收购蔡司公司的一台 Pascal共聚焦显微镜配备短波长（405 nm）和可见波长激光， 激发全细胞膜片钳记录装置可用于进行单细胞膜片钳记录。 电生理学与共聚焦活细胞成像同时进行。这台显微镜， 在医学院院长办公室机构资金的帮助下获得，位于 加州大学洛杉矶分校在同一建筑物的蔡司510 Meta共焦，并已广泛用于服务 复员方案协调委员会调查员。我们的服务也得到了升级，增加了新的成像 活细胞中的技术，包括量子点（Q-dots），光活化蛋白质和 第二信使的生物传感器标记有荧光标签。这些重大改进将 进一步提高我们在细胞和亚细胞水平上观察大分子的能力， 细胞激活后第二信使系统的变化。奥斯瓦尔多·雷伊博士将加入 作为核心联合主任的人员，负责监督新的成像方法， 许多DDRCC调查人员的新需求。 最后，CURE：DDRCC可用的共享资源将得到更多的使用 调查人员通过核心主任和加州大学洛杉矶分校现有核心的安排， 由病理学和实验室医学系，脑研究所和 纳米技术研究所这些互动将继续是形态学的主要努力， 细胞成像核心，以提高核心的技术能力，并确保最佳利用 UCLA社区内的共享资源，包括CURE：DDRCC社区。 总的来说，增加的服务在上文中简要概述，并在正文的后面进行了更详细的解释。 反映了DDRCC研究兴趣和重点的演变，以及 形态学和成像技术。这些新增内容将提供最先进的方法， 许多CURE：DDRCC研究人员有兴趣阐明基本的正常情况， 或控制消化功能的不同类型细胞的异常机制。

The Morphology and Cell Imaging Core has been providing expertise, technical support and assistance for morphological and imaging approaches as well as state-of-the-art equipment for sophisticated imaging techniques to the DDRCC members for over 18 years under the leadership of Dr. Sternini. The services provided by the core have been instrumental for studies that have elucidated the tissue and cellular distribution of signaling molecules that play a role in the control of gastrointestinal (Gl) function and in the pathogenesis of Gl disorders as well as for visualizing signaling pathways that regulate cellular functions. The studies that have benefited from the core have made important advances in our understanding of functional interactions between neuronal and hormonal pathways regulating Gl functions and have resulted in many publications and in long-lasting collaborations. There have been several additions and updates in services throughout the years to reflect the needs of DDRCC members and the evolving of morphological and imaging technologies, with the goal of enhancing the Core capabilities. Enhancement of morphological capabilities includes 1) the addition of mouse pathology services and 2) the incorporation of a Central Bank of well characterized antibodies. The mouse pathology services have been added in our previous competitive renewal in response to the increasing need of many CURE: DDRCC investigators for expertise and assistance in defining phenotypical abnormalities or pathologies that can be detected in genetically manipulated mice, which are increasingly used at CURE:DDRCC. Dr. Nora Rozengurt, an experienced veterinary pathologist with extensive expertise in natural and experimentally induced mouse pathology has been serving as Core Associate Director to supervise this service, which has been extensively used during the past funded cycle. The antibodies central bank has been added to provide a centralized system for the wealth of antibodies that have been produced at CURE during previous funding periods and for other antibodies that are used by many investigators as markers for specific cell types or intracellular signaling molecules. The availability of a centralized bank of well characterized and validated antibodies of interest to CURE: DDRCC investigators is a powerful resource that will allow an effective access of CURE:DDRCC investigators to a variety of reagents that can be utilized through the Morphology and Cell Imaging Core. Dr. Gordon Ohning will join the Core as Associate Director to be in charge of the maintenance of the Central Bank of antibodies. There has been a significant enhancement of the capabilities of our imaging services, including 1) the addition of highly sophisticated equipment and 2) the incorporation of new imaging technologies that will further advance our ability to visualize molecules at the cellular and subcellular levels and changes in second messenger systems following cellular activation. A major enrichment of our imaging facilities has been the addition of a state-of-the-art confocal microscope, a Zeiss LSM 510 Meta equipped with sophisticated software (e.g. deconvolution, image analysis, 3-D rendering) for live and fixed cell imaging. This system was acquired with the help of institutional funds from the David Geffen UCLA School of Medicine just prior to the previous competitive renewal, and since then it has been used heavily by an increasing number of CURE: DDRCC investigators. During the past funded cycle, we have also enhanced our instrumentation for calcium imaging by acquiring a Zeiss Pascal confocal microscope equipped with both short (405 nm) and visible wavelength lasers for excitation. A whole cell patch clamp recording setup is available to perform single cell electrophysiology simultaneously with confocal live cell imaging. This microscope, which has also been acquired with the help of institutional funds from the School of Medicine Dean's office, is housed at UCLA in the same building as the Zeiss 510 Meta confocal and has been extensively used by severa DDRCC investigators. Our services have also been upgraded by the addition of new imaging technologies in live cells, including quantum dots (Q-dots), photoactivatable proteins and second messengers' biosensors labeled with fluorescent tags. These significant improvements will further advance our ability to visualize macromolecules at the cellular and subcellular levels and changes in second messenger systems following cellular activation. Dr. Osvaldo Rey will join the Core personnel as Core Co-Director to supervise the new imaging methodologies that are proposed to cover the new needs of many DDRCC investigators. Finally, there will be an increased use of shared resources that are available for CURE: DDRCC investigators through arrangements made by the Core Director and existing Cores at UCLA, which are supported by the Department of Pathology and Laboratory Medicine, the Brain Research Institute and the Nanotechnology Institute. These interactions will continue to be a major effort of the Morphology and Cell Imaging Core to enhance the technical capabilities of the Core and ensure optimal utilization of shared resources within the UCLA community that includes the CURE: DDRCC community. Overall, the addition of services briefly outlined above and explained in more detail later in the body of the application reflects the evolving of the DDRCC research interests and focus, and the advances in morphological and imaging technologies. These additions will provide state-of-the-art approaches and equipment to many CURE: DDRCC investigators who are interested in elucidating fundamental normal or abnormal mechanisms in different types of cells controlling digestive functions.