Diogo Soares. Linking autism related mutations in Shank3 over synaptic, network and behaviour defects

Motivation
Alterations in glutamatergic synaptic transmission are a prominent feature of numerous forms of autism spectrum disorders (ASD). In particular, mutations in synaptic protein genes such as Shank3 and others have been identified as risk factors for ASD. Shank3 has been identified as a major synaptic organizer, however, surprisingly little is known yet on the mechanistic links between the molecular impact of Shank3 mutations on synapse organization and synaptic function.

Research Challenge
To gain insightful knowledge about those mechanistic links, we will perform a nanoscale dynamic analysis of glutamatergic synapse organization in hippocampal neurons in primary culture and organotypic slices, in various models of Shank3 related ASD. We will correlate these studies to analysis of synaptic function to propose a multi-scale link between the nanoscale synapse disorganization to synapse function and circuit properties in models of ASD.

The group of Dr. Daniel Choquet at the Interdisciplinary Institute for Neuroscience (IINS), University of Bordeaux has a unique joint expertise on high-resolution imaging of synapse organization, analysis of synapse function and circuit properties. Extensive state of the art facilities for advanced microscopy are available at both IINS and the University of Bordeaux.

Requirements
General Requirements apply.

Supervision and Secondments
The PhD project will be carried out in the Dynamic organization & Function of Synapses research group at IINS headed by Daniel Choquet. The ESR will enrol in the Life & Health Science Doctorate School of the University of Bordeaux. The project also features secondments (extended stays) at CNC (Ana Luísa Carvalho) and Eurotrials (now CTI; Sr. Director Ana Cláudia Patacão).

Supervisor(s): Daniel Choquet (daniel.choquet@u-bordeaux.fr), Eric Hosy

Host Location: Interdisciplinary Institute for Neuroscience (IINS) – CNRS, Bordeaux University, Bordeaux, France.

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