Cellular Architecture

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Cellular Architecture

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TEAM LEADER

The proper spatial organization and shaping of the endomembrane system is essential for its functionality:

The fine tubules of the ER stretching throughout the cytosol allows for constantly exchanging lipids with other organelles.

The intraluminal vesicles of the late endosome allow for the transport of to-be-degraded membrane proteins to the lumen of the lysosome.

The stacking of its cisternae reduces the surface of the Golgi apparatus that is available for vesicular budding. This reduces the transport velocity through it and provides its resident enzymes with enough time to properly modify all glycoproteins passing them by.

Our team is interested in how shapes and positions of these and other cell components are generated and maintained. We are convinced that a holistic understanding of this cellular architecture can only be achieved by visualizing the machinery that organizes it. To do this under the most native conditions and at (sub-) nanometer resolutions, we rely on cryo-electron tomography and subtomogram averaging performed on cellular specimen that were thinned down by focused ion beam-milling. In situ structural and ultrastructural insights obtained by this workflow can then serve as framework for the integration of results we gather from reverse genetics, light microscopy, biochemistry, and in vitro structural approaches.

Members

Researchers

Florian FAESSLER

Engineers

Chantal WEBER

Current projects

Project waiting for a PhD student:

Deciphering (ultra)structural mechanisms of Golgi organization

Proper glycosylation of proteins in the endomembrane system is crucial for many biological processes, such as lysosomal sorting, extracellular matrix structuring, and signal transduction. Improper glycosylation, in turn, is associated with neurodegeneration, cancer, and autoimmune diseases. It is, thus, vital for cells to maintain the order of their central glycan modification hub, the Golgi apparatus.

In this context, the Golgi matrix, in concert with other players like the cytoskeleton, guides protein distribution amongst the individual Golgi cisternae, controls their shape, and keeps them stacked. Nevertheless, how the Golgi matrix itself is structured to achieve these functionalities remains largely unknown, as the usability of classical approaches based on fluorescence microscopy, room temperature electron microscopy, and in vitro reconstitution is limited by the small size and high complexity of the system. To overcome this, we will employ state-of-the-art in situ cryo-electron tomography to visualize the Golgi matrix and its interactors. Applying subtomogram averaging to selected players will further allow us to determine their structures at (sub-) nanometer resolution in their intracellular environment.

This will provide an (ultra-) structural framework for the integration of orthogonal data provided by reverse genetics, cell biology, and biochemistry techniques. Together, we will use these approaches to provide unprecedented insights into the structure-function relationship of the Golgi apparatus organization.

We offer:

• Training covering complete in situ structure biology workflows from specimen preparation to structure determination and quantitative
ultrastructural analysis

• Training for

establishing genome-edited cell lines

performing live cell imaging and immunofluorescence microscopy

• Access to state-of-the-art cryo-electron and light microscopes

• A supportive work environment

• Participation in scientific conferences

• Access to courses at the Doctoral School of Life and Health Sciences of the University of Strasbourg

If this matches your profile:

• Master's degree in cell biology, biochemistry, or a related field

• Practical experience in two or more of the following

structural biology techniques

electron/light microscopy