CAREER: Defining novel pathways for mitochondrial dynamics in an early-diverging eukaryote

在这个项目中，研究人员将让高中生、本科生和研究生参与尖端细胞生物学研究，以发现细胞内的隔间如何随着营养的可获得性而改变形状。线粒体是复杂细胞中大量存在的产生能量的隔间。线粒体在不同的细胞类型中具有独特的形状，与功能密切相关。线粒体的形状也是高度动态的，可以很容易地改变以适应不同的能量需求。为了发现建立和维持线粒体形状的共同机制，研究人员将使用一组被称为动体的单细胞寄生虫的模型生物。动质体不同寻常，因为每个细胞只含有一个线粒体，当寄生虫在昆虫和哺乳动物宿主之间交替时，线粒体在结构和功能上经历了戏剧性的变化。这种安排极大地方便了对线粒体结构变化的分析，并将揭示细胞控制其线粒体数量和分布的共同机制。由于它们的进化地位，动体拥有一套基本的线粒体形状蛋白，对这些蛋白的研究将有助于深入了解这些过程如何在各种类型的细胞中发挥作用。为了更好地理解这些复杂的结构，工科学生将使用3D打印机创建线粒体模型。这项跨学科的工作将阐明工程学和生物学之间的联系，并将展示如何将这项技术应用于增强对细胞生物学基本问题的理解和交流。动体寄生虫，如束状克里迪亚线虫和布氏锥虫，长期以来一直是基本细胞过程的重要模型。尤其是动叶绿体线粒体具有不同寻常的特征，包括每个细胞只有一个线粒体的事实。这就需要一种迄今未知的机制来调控细胞周期内线粒体的生物发生和分裂。此外，在寄生虫的不同生命周期阶段，线粒体的形状和功能会发生显著和可逆的变化。在其他生物中，线粒体的形状是通过膜融合和裂变事件来建立和维持的，统称为线粒体动力学。虽然在酵母和人类中已经描述了线粒体动力学的大部分机制，但这些过程是如何调节的还不是很清楚，而且并不是所有的线粒体动力学蛋白都是保守的。研究人员将使用各种细胞和分子生物学技术来确定控制动质体内线粒体形状的机制，为这些过程是如何进化的以及它们在其他生物体中的功能提供重要的见解。

In this project, the investigators will engage high school, undergraduate, and graduate students in cutting-edge cell biology research to discover how compartments within cells change shape in response to nutrient availability. Mitochondria are energy-generating compartments present in large numbers in complex cells. Mitochondria have a characteristic shape in different cell types, which is closely correlated to function. The shape of mitochondria is also highly dynamic, and can readily shift to adapt to different energy requirements. To discover shared mechanisms for establishment and maintenance of mitochondrial shape, the researchers will use model organisms from a group of single-celled parasites called the kinetoplastids. Kinetoplastids are unusual in that each cell contains only a single mitochondrion that undergoes dramatic changes in structure and function as the parasites alternate between insect and mammalian hosts. This arrangement greatly facilitates the analysis of changes in mitochondrial structure, and will reveal shared mechanisms by which cells control the number and distribution of their mitochondria. Due to their evolutionary position, kinetoplastids possess a basal set of mitochondrial shape proteins, the investigation of which will provide insight into how these processes work in a wide variety of cell types. To allow for better understanding of these complex structures, engineering students will create mitochondrial models using a 3-D printer. This interdisciplinary effort will illustrate the connections between engineering and biology, and will demonstrate how this technology may be applied for enhanced understanding and communication of fundamental questions in cell biology.Kinetoplastid parasites such as Crithidia fasciculata and Trypanosoma brucei have long been important models for basic cellular processes. Kinetoplastid mitochondria in particular have unusual features, including the fact that there is only one mitochondrion per cell. This necessitates a thus far unknown mechanism for regulation of mitochondrial biogenesis and division within the cell cycle. In addition, the shape and function of the mitochondrion are dramatically and reversibly altered in different life cycle stages of the parasite. In other organisms, mitochondrial shape is established and maintained by membrane fusion and fission events, collectively called mitochondrial dynamics. While much of the machinery for mitochondrial dynamics has been described in yeast and humans, how these processes are regulated is not well understood, and not all mitochondrial dynamics proteins are conserved. The investigators will use a variety of cellular and molecular biology techniques to identify the mechanisms controlling mitochondrial shape in kinetoplastids, providing important insight into how these processes evolved and their function in other organisms.