PostDoc position - IGBMC - Team Faessler

Cryo-electron tomography (cryo-ET) can provide unique ultrastructural insights into the molecular architecture of natively preserved cells. Combining it with subtomogram averaging (STA) allows for determining subnanometer resolution structures in situ. However, localizing proteins of interest (POIs) within cells during data acquisition and processing remains a bottleneck for this approach. Fluorescently tagged POIs for cryo-correlative light and electron microscopy (cryo-CLEM) can guide lamella preparation and data acquisition. However, fluorescence microscopy (FM) data will typically not support identifying POIs in cryo-electron tomograms for further processing.  
Thus, a tagging approach marking proteins in both imaging modalities would be highly desirable. At best, the resulting label should be able to recruit membrane-permeable synthetic fluorophores to allow for reliable detection of POIs at endogenous expression levels in FM, result in a uniquely shaped strong density in cryo-ET, and cause neglectable perturbations for cell physiology and protein function. This project aims to provide a genetically encoded two-component cryo-CLEM labeling system that can meet those challenging demands.  

Our team is interested in how cells establish, maintain, and alter the shapes and orientations of their large-scale components, like organelles or the cytoskeleton. 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-ET and STA performed on cellular specimens. In situ structural and ultrastructural insights obtained by this workflow can then serve as a framework for integrating results we gather from reverse genetics, light microscopy, biochemistry, and in vitro structural approaches.

Department of Integrative Structural Biology (BSI) at the Institute of Genetics and Molecular and Cell Biology (IGBMC) has a strong focus on cryo-electron microscopy (cryo-EM) techniques and houses 2 Titan Krios, 1 Glacios, 1 cryo-Focused Ion Beam Scanning Electron Microscope (cryo-FIB/SEM), a cryo-light microscope, several vitrification devices (plunge freezing and high-pressure freezing) and a dedicated micromechanics workshop for developing and prototyping new instruments.  

IGBMC hosts many working with cellular model systems for a wide variety of developmental, homoeostatic, and pathologic processes, which are amenable to characterization by cryo-CLEM-guided cryo-ET but have yet to be explored by this methodology. This will provide the PostDoc with ample opportunities for in-house collaborations.
We will support the postdoctoral fellow in the application for prestigious fellowship schemes (Marie Skłodowska-Curie, EMBO, HPSF) and scientific prices.
The institute is located next to the beautiful city of Strasbourg (with a world-famous Christmas market) in the Alsace region of France, close to the German border and within a short distance to the Black Forrest and the Vosges mountain ranges boasting ample opportunities for recreational activities.   

Associé à :

• Équipe(s) : Architecture Cellulaire