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The structural basis of neurodegeneration, and structural analysis of membrane proteins

We investigate molecular mechanisms associated with the development of neurodegenerative diseases. We also study membrane proteins in the lipid membrane embedded state, using cryo-EM as main tool.

Parkinson's disease
We are approaching Parkinson’s disease and other neurodegenerative diseases with a multi-disciplinary approach. Here, we combine cryo-electron microscopy (cryo-EM), cryo-electron tomography (cryo-ET), correlative light and electron microscopy (CLEM), microfluidics, neuronal cell cultures, and other biophysical tools. We study several molecules involved in these diseases (e.g., alpha-synuclein, tau, TDP-43, etc.) in collaboration with partners from other institutes, aiming for their atomic structure in complex or fibrillar forms. We also cultivate neuronal cell cultures in microfluidic chips, which we use for seeding experiments with pre-formed fibrils or oligomers of proteins or neurodegenerative factors. And finally, we study the morphology of human post-mortem brain from deceased patient tissue donors.

Biological membrane systems
We are studying the structure and conformational states of several transporter and ion channel membrane proteins. Here, we collaborate with other laboratories in Switzerland and internationally, as well as with the company leadXpro ( 

Methods development. 
We develop imaging protocols (CLEM) and data analysis software tools to increase resolution and to accelerate the structure determination pipeline for cryo-EM and cryo-ET. We are also developing a microfluidic tool chain for single cell visual proteomics and cryo-EM grid preparation. 

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