Advanced microscopy system for real-time imaging of cellular dynamics during animal development

*朱莉·布里尔博士的前沿研究项目旨在了解细胞在发育过程中改变形状(经历形态发生)和分化的分子过程。她的实验室的一个主要重点是研究精子发育过程中控制细胞形态发生和分化的机制，这是一个对男性生育能力至关重要的过程。布里尔博士的实验室使用果蝇模型系统(果蝇黑腹果蝇)强大的分子遗传学和特征完善的细胞生物学来描述伴随成熟精子形成而发生的戏剧性变化。使用显微镜，她的实验室可以检查当不育果蝇的精子成熟过程受到影响时发生的缺陷。布里尔博士是世界上为数不多的研究果蝇精子发育的细胞生物学的科学家之一。*该提案要求为布里尔博士的实验室(2016 NSERC发现拨款获得者)提供关键设备。为了使布里尔博士的实验室能够继续NSERC资助的研究，需要一个全面的显微镜系统，包括倒置荧光显微镜和高灵敏度相机。这种新的显微镜将配备用于对分化细胞和组织进行长期实时和3D成像，揭示前所未有的亚细胞细节。例如，通过对带有荧光标记的RNA分子、蛋白质和脂质进行成像，布里尔博士的实验室将研究这些物质在细胞形态发生过程中是如何受到调控的，以确保产生成熟、可生育的精子。该设备还将允许对培养的细胞和组织进行定量成像，从而能够进行快速筛选，以确定控制细胞形态形成和分化的特定途径的因素。*建议的设备将最大限度地增加布里尔博士的NSERC发现赠款的投资，并使最先进的技术能够研究发育过程中细胞形态形成和分化的动力学和亚细胞结构。由于布里尔博士目前的显微镜已有18年的历史，不能再进行维修或保养，因此迫切需要这种设备。此外，由于需要快速接触显微镜，以及长期的实时成像实验，她的实验室不能使用位于大楼其他地方的其他显微镜来进行这项研究。这些设备将有助于培训一批高素质的人员(本科生、研究生、博士后)，将复杂的分子遗传学方法与同样复杂的显微镜成像技术结合起来，揭示新的细胞机制，这将进一步加深我们对动物发育和男性生育的基本过程的理解。

****** Dr. Julie Brill's cutting-edge research program aims to understand the molecular process by which cells change shape (undergo morphogenesis) and differentiate during development. A main focus of her lab is to investigate mechanisms that control cell morphogenesis and differentiation during sperm development, a process that is essential for male fertility. Dr. Brill's lab uses the powerful molecular genetics and well-characterized cell biology of the fruit fly model system (Drosophila melanogaster) to characterize the dramatic changes that accompany formation of mature sperm. Using microscopes, her lab can examine defects that occur when the sperm maturation process is compromised in infertile flies. Dr. Brill is one of the few scientists world-wide that are studying the cell biology of Drosophila sperm development. ****** This proposal requests crucial equipment for Dr. Brill's lab (2016 NSERC Discovery Grant recipient). A comprehensive microscopy system, including an inverted fluorescence microscope and high-sensitivity camera, are requested to enable Dr. Brill's lab to continue NSERC-funded research. This new microscope will be outfitted for long-term live- and 3D-imaging of differentiating cells and tissues in real time, revealing unprecedented subcellular detail. For example, through imaging fluorescently-tagged RNA molecules, proteins and lipids, Dr. Brill's lab will examine how these are regulated during cell morphogenesis to ensure the production of mature, fertile sperm. This equipment will also permit quantitative imaging of cultured cells and tissues, allowing for rapid screening to identify factors that control specific pathways involved in cell morphogenesis and differentiation. ****** The proposed equipment will maximize the investment of Dr. Brill's NSERC Discovery Grant and enable state-of-the art technology for studying the dynamics and subcellular architecture of cell morphogenesis and differentiation during development. This equipment is urgently needed, as Dr. Brill's current microscope is 18 years old and can no longer be repaired or serviced. Moreover, due to the need for rapid access to the microscope, as well as the duration of long-term live imaging experiments, her lab cannot use other microscopes located elsewhere in the building to conduct this research. The equipment will contribute to training a group of highly qualified personnel (undergraduates, graduate students, postdoctoral fellows) to combine sophisticated molecular genetic approaches with equally sophisticated microscope imaging techniques to uncover novel cellular mechanisms that will further our understanding of fundamental processes involved in animal development and male fertility.*****