Integrative mechanisms of organelle dynamics from the atomic-to-cellular level

项目总结 此RM1提案侧重于定义和描述支持以下各项的集成系统 细胞内细胞器的运输和放置。与其仅仅将“分子”描述为 生物物理学家或“细胞器动力学”作为细胞生物学家，我们的目标是实现从原子到细胞器的 细胞器转运机制的细胞到活体水平的理解。我们的 协作和多学科的研究团队将发现和研究原住民 细胞内和体外的微环境，通过考虑与生理相关的组合 控制细胞器的分子马达、细丝、适配器、膜和其他辅助因子 运动和极化。我们将使用线粒体作为我们的初始模型系统，因为许多关键 对这种细胞器的动力学至关重要的分子和信号通路有 已经描述过了。我们将揭示空间组织和动态的作用 灯丝的装配、机械力、马达活动等调节要素将 调查过了。我们将在体外重建复杂的微环境，以确定运动和 锚定机构。我们将对这些系统进行计算建模并进行实验测试 直接在细胞内和体内建立模型。我们的研究团队将通过以下方式得到鼓舞和扩充 实施探索性试点研究计划，将有希望的早期阶段- 调查人员加入我们的合作团队。

PROJECT SUMMARY This RM1 proposal focuses on defining and characterizing the integrated systems that support intracellular organelle transport and placement. Rather than just characterizing “molecules” as biophysicists or “organelle dynamics” as cell biologists, our goal is to achieve an atomic-to- cellular-to-in vivo level understanding of the mechanisms of organelle transport. Our collaborative and multi-disciplinary research team will discover and study the native microenvironments in cells and in vitro, by considering physiologically-relevant combinations of molecular motors, filaments, adaptors, membranes and other cofactors that control organelle movement and polarization. We will use mitochondria as our initial model system, as many key molecules and signaling pathways that are essential for the dynamics of this organelle have already been described. We will uncover the roles of spatial organization and dynamic assembly of filaments, mechanical forces, motor activity, and other regulatory elements will be investigated. We will reconstitute complex microenvironments in vitro to determine motile and anchoring mechanisms. We will computationally model these systems and experimentally test models directly in cells and in vivo. Our research team will be energized and expanded by implementing an Exploratory Pilot Studies Program to incorporate promising early-stage- investigators into our collaborative team.