Team "Intracellular Dynamics and Neurodegeneration"

Themes of research

The Team "Intracellular Dynamics and Neurodegeneration" has proposed a major role of HTT in the regulation of fast axonal transport (FAT) and found that HTT regulates efficacy and the directionality of FAT through phosphorylations. In addition the team has shown that these phosphorylations restore FAT in the disease situation.

Huntingtin protein mutation consists in the addition of an abnormally high number of the amino acid Glutamine which creates a polyGlutamine repetition. This expansion is at the origing of Huntington's Disease, a rare hereditary neurodegenerative disorder rare that progressively leads to motor deficits, cognitive decline ans psychiatric troubles.

To better understand the molecular mechanisms by which the huntingtin protein regulates intracellular dynamics and neuronal functions, the team works around these two research projects :

• Studying the normal functions of huntingtin and its role on neuronal functions : To better understand how huntingtin controls vesicular transport in axons and the consequences on physiological functions of the neuron.

• Dysfunctional consequences of polyGlutamine expansion : To determine how abnormal repetition of Glutamines alters the normal functions of hutingtin and the consequences on intracellular dynamics.

Techniques utilisées :

• Cell and molecular biology : primary cultures of neurones, expression of recombinant proteins, protein-protein interactions, fluorescent probes and sensors

• Microscopy : spinning-disk videomicroscopy, confocal, super-resolution, 2-photon

• Microfluidics : neuronal networks, axonal transport, synapses, axonal growth

• Electrophysiology : microelectrode arrays, patch clamp, optogenetics

• Development of drosophila and transgenic mice : knock-in, mutants, Huntington models

Partners :