RUI: Exploring the Function of FtsZs and the Cytoskeleton to Determine the Molecular Mechanism of Mitochondrial Dynamics in Dictyostelium discoideum

细胞线粒体调节许多过程，如钙水平和细胞程序性死亡。然而，它们最为人所知的是能量传递，通常被称为细胞的动力源。这个项目的重点是线粒体结构，因为如果没有合适的结构，线粒体就会功能失调。虽然线粒体是从祖先的细菌细胞发展而来的，但不同的生物(如人类、阿米巴、藻类、酵母等)以不同的方式维持线粒体结构。如果我们能够理解这些生物体维持结构的机制，我们就可以了解为什么这些机制不同，同时也可以洞察线粒体功能障碍的原因。该项目的更广泛影响包括这项工作的内在价值，因为绝大多数真核细胞都含有这些细胞器。其他活动将有K-16岁的学生参加。阿肯色州中部一所以本科生为主的大学的学生将开展这一项目。接触高质量、资金充足的研究为学生提供了探索研究是否适合他们的职业选择的能力。它为学生准备博士课程，在研究方面指导学生对于留住那些在STEM中传统上代表性较低的群体至关重要。除了培训本科生外，该项目还包括向K-6学生提供服务。该计划是与当地小学正式建立关系，特别是那些ACT Aspire分数显示科学不足的小学。通过动手活动与K-6学生进行互动，旨在启发学生，向他们展示科学是有趣的，并继续发展他们的科学探究技能。线粒体的基本功能依赖于它们的结构，而结构又依赖于线粒体的动力学、分裂、融合和运动。在许多细胞类型中，如哺乳动物和酵母细胞，一个被称为动力蛋白相关蛋白(DRPs)的蛋白质家族维持着高度相互连接的线粒体网络。重要的是，我们的模式生物盘基网柄菌不使用DRPS来调节线粒体动力学。相反，盘状芽孢杆菌基因组编码两种蛋白质FszA和FszB，这两种蛋白质来自细菌细胞分裂蛋白FtsZ。目前还不清楚为什么一些生物使用DRP，而一些生物使用似乎来自FtsZ的蛋白质。这项研究的一个长期目标是了解盘状芽孢杆菌线粒体动力学的分子机制，以便确定一些生物在进化过程中何时以及为什么用DRP取代FtsZ。第一个项目的目标是确定现有的FtsZ在线粒体动力学中的作用，并将涉及改变蛋白质水平，识别相互作用的蛋白质，并分析FtsZ的结构复合体。最近的工作表明，细胞骨架是线粒体动力学调节的主要参与者，该项目的第二个目标是通过识别分裂/融合事件以及细胞骨架被破坏时的运输速度来研究细胞骨架与线粒体动力学的关系。该项目的完成将有助于确定FtsZ是否像DRP一样发挥功能，以及盘状芽孢杆菌细胞骨架如何调节线粒体动力学。最终，这项工作将有助于理解线粒体和线粒体动力学的进化，特别是为什么一些生物使用DRP和一些生物使用FtsZ。该项目由分子和细胞生物科学部和既定的刺激竞争研究计划(EPSCoR)联合资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Cellular mitochondria regulate many processes, such as calcium levels and programmed cell death. However, they are best known for energy transduction and are often referred to as the powerhouse of the cell. This project focuses on mitochondrial structure because without appropriate structure, mitochondria become dysfunctional. Although mitochondria developed from an ancestral bacterial cell, different organisms (e.g., humans, amoeba, algae, yeast, etc.) maintain mitochondrial structure in different ways. If we can understand the mechanisms that maintain structure across these organisms, we can learn why the mechanisms are different while also gaining insight into the causes of mitochondrial dysfunction. The broader impacts of this project include the intrinsic merit of the work as the vast majority of eukaryotic cells contain these organelles. Other activities will involve K-16 students. Students at a primarily undergraduate university in central Arkansas will carry out this project. Exposure to quality, well-funded research provides students the ability to explore whether research is an appropriate career choice for them. It prepares students for doctoral programs, and mentoring students in research is critical for retention of those from groups traditionally underrepresented in STEM. In addition to training undergraduates, this project involves outreach to K-6 students. The plan is to formalize relationships with local elementary schools, specifically ones whose ACT Aspire scores indicate a deficit in science. Interactions with K-6 students via hands-on-activities are designed to inspire students, show them that science is fun, and continue to develop their scientific inquiry skills. The essential functions of the mitochondria are dependent upon their structure, which, in turn, is dependent upon mitochondrial dynamics, fission, fusion, and motility. In many cell types such as mammalian and yeast cells, a protein family known as dynamin-related proteins (DRPs) maintains the highly interconnected network of mitochondria. Importantly, our model organism, Dictyostelium discoideum does not use DRPs to regulate mitochondrial dynamics. Rather, the D. discoideum genome encodes two proteins, FszA and FszB, which are derived from the bacterial cell division protein, FtsZ. It is not understood why some organisms use DRPs and some use what appears to be derived FtsZ proteins. A long-term goal of this research is to understand the molecular mechanism of mitochondrial dynamics in D. discoideum in order to identify when and why some organisms replaced FtsZs with DRPs as they evolved. The first project goal is to identify the role of extant FtsZs in mitochondrial dynamics and will involve altering protein levels, identifying interacting proteins, and analyzing FtsZs structural complexes. Recent work has shown that the cytoskeleton is a major player in the regulation of mitochondrial dynamics, and the second goal of this project is to study the relationship of the cytoskeleton with mitochondrial dynamics by identifying fission/fusion events, along with transport velocities when the cytoskeleton is disrupted. Completion of this project will help determine if FtsZs function like DRPs, and how the D. discoideum cytoskeleton regulates mitochondrial dynamics. Ultimately, this work will contribute to understanding the evolution of mitochondria and mitochondrial dynamics and specifically why some organisms use DRPs and some use FtsZs.This project is jointly funded by the Division of Molecular and Cellular Biosciences and the Established Program to Stimulate Competititive Research (EPSCoR).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.