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PhD position : « Decoding the interplay between autophagy and exosomes at the synapse »

The Soukup team is looking for a talented PhD candidate to join our team and to investigate the interplay between autophagy and exosomes in neurons using Drosophila as animal organisms.

We offer a fully funded PhD position in our international and friendly team placed at the Institute for neurodegenerative diseases at the Bordeaux Neurocampus. The position is immediately available and the starting date is October 1st 2019.

The candidate has ideally been selected for the Bordeaux doctoral school or has outstanding qualifications from the master. You have high motivation and dedication to pursue a career in Science and have an interest in neuroscience and cell biology.

Project description

Synapses are the communication centers of the neuron but they are especially vulnerable to the accumulation of dysfunctional proteins. To ensure synaptic transmission, local synapse specific mechanisms take place to cope with proteopathic stress and to restore synaptic homeostasis.

Accumulation of dysfunctional, damaged or mutated proteins can promote the formation of aggregates. In macroautophagy, here referred as autophagy, dysfunctional cellular elements are engulfed by a membrane forming the autophagosome and sent for degradation to the lysosome. We have already reported that synaptic autophagy is controlled by local specific adaptations (Soukup et al., Neuron, 2016; Vanhauwaert et al, Embo J., 2017). However, while in the cell body the regulatory mechanisms controlling autophagy are being elucidated, little is known about how autophagy controls protein rejuvenation and aggregate clearance at the level of the synapses.

Quality control at the synapse not only relies on the function of lysosomes and autophagosomes. Indeed, exosome release has also been implicated in the disposal of dysfunctional proteins and in neurodegenerative diseases. Exosomes are extracellular vesicles, derived from endocytic compartments. In non-neuronal cells, metabolic induction of autophagy inhibits exosome release while inhibition of autophagy favours that process. However, we have little information about the interplay of autophagy and exosome release at the synapse, especially during the onset of neurodegeneration. Both the maturation of autophagosomes as well as the exosomes require of late endosomes and preliminary results from our laboratory shows this is also true at the synapse, where autophagosomes fuse with Rab7 positive late endosomes (Soukup, unpublished).

We have also preliminary data at presynaptic terminals showing that after autophagy induction more MVBs are fusing with the plasma membrane to secrete exosomes (Soukup unpublished). Since both mechanisms rely on the availability of MVBs, we hypothesize that both processes are interconnected at the synapse. Moreover, we predict that local imbalance between these two processes at the synapse could be at the root of neurodegeneration. Thus, deciphering the interplay of autophagy and exosome release at the synapse seems essential to understand the early onset of neurodegenerative diseases like PD.

How to apply?

Send a motivation letter and CV directly to rf.xu1563421527aedro1563421527b-u@p1563421527ukuos1563421527.ardn1563421527as1563421527

More information and selected publications:

https://www.bordeaux-neurocampus.fr/team/molecular-mechanisms-of-synaptopathies/

https://www.imn-bordeaux.org/en/teams/molecular-mechanisms-of-synaptopathies/

10/07/19