A Long Path to Power: combining bioengineering, stem cells and cell biology to uncover the mysteries of axonal biology

权力之路漫漫：结合生物工程、干细胞和细胞生物学，揭开轴突生物学的奥秘

• 批准号: 2723028
• 金额: --
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2723028
• 关键词: Long; Path; Power; combining; bioengineering

For the PhD project we will build upon previous results from our recent publications aswell as from the optimisation of the imaging for ER mitochondria structures performedduring the rotation to focus on the following questions: - How does axonal length affectthe overall metabolism and function of the neurons? - How does ER organisationchange with axonal length? - How does ER-mitochondria organisation evolve as theaxons elongate? - How does the neuronal cell type affect the length dependent ER andmitochondria changes? Our recent work lead to the discovery that in human neuronslength-dependent regulatory mechanisms adapt neuronal mitochondrial andtranslational profiles to sustain the growing axons. This is a fundamental newdiscovery made possible by the combination of stem cell modelling, live imaging andon chip modelling with bioengineered devices. We are now interested in exploring themolecular pathways that lead to these length-dependent adaptations, but we aremissing a key player: the ER. In fact, the ER is the largest of all organelles (particularlyas it span the whole axon), it is responsible for several key function in axonalhomeostasis, and regulates mitochondrial dynamics via ER-mitochondrial contactpoints. We also know that ER dynamics vary along the axons and that different celltypes have different mechanism to control ER-mitochondrial interactions. With thisproject we will explore in details these dynamics, and uncover how specific subtypes ofneurons and different axonal length affect the ER. Dr. Serio will be primary supervisorand provide expertise in neuronal cell biology, bioengineering and imaging; Dr. Devinewill provide expertise in stem cell differentiation and mitochondrial biology.

对于博士项目，我们将建立在以前的结果，从我们最近的出版物，以及从优化的成像ER线粒体结构performedduring旋转集中在以下问题：-轴突长度如何影响整体代谢和功能的神经元？- 内质网结构如何随轴突长度变化？- 当轴突伸长时，内质网-线粒体组织是如何进化的？- 神经元细胞类型如何影响ER和线粒体长度依赖性变化？我们最近的工作发现，在人类神经元长度依赖性调节机制适应神经元线粒体和翻译的档案，以维持不断增长的轴突。这是一项基本的新发现，通过将干细胞建模、实时成像和芯片建模与生物工程设备相结合而成为可能。我们现在有兴趣探索导致这些长度依赖性适应的分子途径，但我们缺少一个关键角色：ER。事实上，ER是所有细胞器中最大的（特别是因为它跨越整个轴突），它负责轴突稳态的几个关键功能，并通过ER-线粒体接触点调节线粒体动力学。我们还知道ER动力学沿着轴突变化，并且不同的细胞类型具有不同的机制来控制ER-线粒体相互作用。通过这个项目，我们将详细探索这些动力学，并揭示特定亚型的神经元和不同轴突长度如何影响ER。Serio博士将担任主要主管，并提供神经元细胞生物学、生物工程和成像方面的专业知识; Devine博士将提供干细胞分化和线粒体生物学方面的专业知识。