• E-mail :[email]
  • Phone : 01 42 86 20 67
  • Location : Paris, France
Last update 2011-05-20 10:45:48.412

Sophie Mouillet-Richard PhD Cell Biology

Course and current status

Education :

1991-1994 Ecole Polytechnique - Diplôme d’Ingénieur Polytechnicien (Masters in Engineering)

1994-1996 Ecole du Génie Rural des Eaux et des Forêts – Post-graduate training

1995-1996 University Paris Sud - Masters degree in Cell Biology (Molecular Biology of the Cell, with honors)

2001 Ecole Polytechnique, PhD in Cell Biology, with honors (Thesis director: Odile Kellermann)

Actual position:

Principal investigator, INSERM Unit 747, University Paris Descartes, France

Scientific summary

We exploit the properties of a neuroectodermal stem cell (1C11) to study the molecules and the signalling pathways that sustain the maintenance of the stem cell state, the onset and the regulation of neuronal functions. The 1C11 cell line has the unique capacity among in vitro cell lines to implement the overall functions of serotonergic (1C115-HT) or noradrenergic (1C11NE) neurons.

Recently, we took advantage of this cellular model to probe for microRNAs that could contribute to the post-transcriptional regulation of neuron-associated functions in differentiating cells. We identified miR-16 that controls the expression of the serotonin transporter (SERT), the target of Serotonin Reuptake Inhibitor (SRIs) antidepressants. miR-16 is expressed at higher levels in noradrenergic than serotonergic cells, both in vitro and in vivo. Treatment with the SRI fluoxetine (Prozac) reduces miR-16 in noradrenergic cells, unlocks SERT expression and renders noradrenergic cells competent to bind SRI antidepressants.

A second project aims at unravelling the function exerted by the cellular prion protein (PrPC) in neuronal homeostasis and the mechanisms sustaining the neurotoxicity of the scrapie prion protein (PrPSc). We focus on the cell signalling pathways associated with PrPC. Using the 1C11 neuronal cell line, we documented that PrPC exerts a ubiquitous role in the control of the redox state and in cellular homeostasis, by activating the ROS-generating enzyme NADPH oxidase, the ERK1/2 MAP kinases and the CREB transcription factor. Our data also show that PrPC has a neurospecific function that relies on the implementation of a PrPC-caveolin-Fyn signalling plateform and that is involved in the regulation of matrix metalloproteases. In 1C115-HT and 1C11NE neuronal cells, we further established a functional link between PrPC and the shedding of TNFa, which in turn promotes neurotransmitter degradation.

Through these projects, our global aim is to understand how the deviation of signalling cascades that normally control cell homeostasis may lead to a pathological state such as depression or neurodegeneration.

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