MULTI-PHOTON IMAGING OF ACTIN FILAMENT FORMATION AND MITOCHONDRIAL ENERGETICS

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 PI 将开发多光子 (MPM) 光学成像方法，以系统地研究嵌入各种 3D ECM 中的人类胶质母细胞瘤多形球体。这些实验性癌症模型系统用于模拟体内神经胶质瘤。 PI 将开发一种基于还原烟酰胺腺嘌呤二核苷酸 (NADH) 和氧化黄素腺嘌呤二核苷酸 (FAD) 固有细胞荧光的 MPM 比率氧化还原荧光法，用于研究线粒体能量代谢。 将这些发现与使用染料对线粒体膜的评估相结合，并将 F-肌动蛋白分布与线粒体信号结合起来可视化，将有助于更好地理解 ECM 如何改变恶性胶质瘤细胞的生长、分化和代谢状态。 开发的成像方法将帮助癌症研究人员研究细胞存活和转移等关键癌症特性，并可以准确测量肿瘤对治疗的反应。拟议的研究将有利于多形性胶质母细胞瘤的当前治疗和预后。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. PI will be developing multiphoton (MPM) optical imaging methods to systematically study human glioblastoma multiform spheroids embedded in various 3D ECMs. These experimental cancer model systems are used to mimic the in vivo gliomas. An MPM ratiometric redox fluorometry method based on intrinsic cellular fluorescence from reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavin adenine dinucleotide (FAD) to study mitochondrial energy metabolism will be developed by the PI. Coupling these finding with the evaluations of mitochondrial membrane using a dye and visualizing F-actin distribution in conjunction with mitochondrial signals will furnish a better understanding on how ECM alters the growth, differentiation and metabolic states of the malignant glioma cells. The imaging methods developed will help cancer investigators to study key cancer properties such as cell survival and metastasis and can allow accurate measurements of tumor response to treatments. The studies proposed will benefit current therapies and prognosis for glioblastoma multiform.