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

点击翻译按钮获取中文摘要

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.