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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
Aging increases both the risk of the development and the rate of progression of neurodegenerative diseases, such as Parkinson’s disease. Although certain proteins, such as alpha-synuclein, are known to play an important role in Parkinson’s disease, the possibly multi-factorial causes of the disease are still unclear. Studying the various forms of alpha-synuclein and other so-called ‘amyloid’ proteins and their transmission from cell to cell, will help to elucidate the mechanisms involved and provide information needed for drug development.

Biological membrane systems
Membrane proteins are incorporated into the lipid bilayer of membranes and are responsible, for example, for supplying our cells with energy and nutrients as well as for expelling molecules that are not required. These import/export functions have to be adjusted precisely to the needs of the cell. Membrane proteins are also involved in cell-cell communication, cell division and in defense mechanisms. Their dysfunction, is related to a wide range of diseases, making them major drug targets. We are studying various membrane proteins using high-resolution cryo-electron microscopy.

Methods and imaging procedures
We combine light and electron microscopes of various types to obtain a comprehensive picture of the specimens at different magnifications. We develop new methods of sample preparation and systems biology analysis to realize correlative microscopy. Moreover, we are improving imaging procedures in electron microscopy, in particular for high-resolution cryo-electron microscopy, and are developing and implementing computer algorithms for the high-resolution 3D reconstruction of protein structure. We are also developing a single cell visual proteomics pipeline to investigate protein aggregation in cell systems.

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