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

For the PhD project we will build upon previous results from our recent publications as
well as from the optimisation of the imaging for ER mitochondria structures performed
during the rotation to focus on the following questions: - How does axonal length affect
the overall metabolism and function of the neurons? - How does ER organisation
change with axonal length? - How does ER-mitochondria organisation evolve as the
axons elongate? - How does the neuronal cell type affect the length dependent ER and
mitochondria changes? Our recent work lead to the discovery that in human neurons
length-dependent regulatory mechanisms adapt neuronal mitochondrial and
translational profiles to sustain the growing axons. This is a fundamental new
discovery made possible by the combination of stem cell modelling, live imaging and
on chip modelling with bioengineered devices. We are now interested in exploring the
molecular pathways that lead to these length-dependent adaptations, but we are
missing a key player: the ER. In fact, the ER is the largest of all organelles (particularly
as it span the whole axon), it is responsible for several key function in axonal
homeostasis, and regulates mitochondrial dynamics via ER-mitochondrial contact
points. We also know that ER dynamics vary along the axons and that different cell
types have different mechanism to control ER-mitochondrial interactions. With this
project we will explore in details these dynamics, and uncover how specific subtypes of
neurons and different axonal length affect the ER. Dr. Serio will be primary supervisor
and provide expertise in neuronal cell biology, bioengineering and imaging; Dr. Devine
will provide expertise in stem cell differentiation and mitochondrial biology.