Cellular Architecture
Cellular Architecture
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
Engineers
Current projects
Project waiting for a PhD student:
Deciphering the (ultra-) structural mechanisms of Golgi stacking
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, a dense protein assembly, 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 combined with subtomogram averaging to visualize the Golgi matrix and its proteins at (sub-) nanometer resolution in its 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.
Funding and partners
Junior Professor Chair (CPJ)
News
Florian Fäßler, new research team leader specialized in cell architecture
Florian Fäßler joins the IGBMC and starts his own research team focused on the inner architecture of cells. Joining the Department of…
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