Cryo-electron microcopy is revolutionising our vision of proteins and the cell (Nobel Prize 2017). One approach, known as isolated particle analysis, makes it possible to build atomic models of purified and homogeneous. At the same time, cryo-tomography (cryo-ET) is being developed to obtain molecular models of more complex samples, in vitro reconstituted or within cells with all the variability present within their assemblies, and to gain a more complete picture of biological function. Cryo-EM images contain high-resolution information (< 2 Å) but with a very low signal-to-noise ratio. Therefore, efforts are being made to develop advanced image analysis and 3D visualization, including deep-learning approaches.
In this context, our team is developing the analysis of protein machinery associated with membranes involved in cell division, cell migration and inter-organelle communication, whose dysfunctions are responsible for cancer and neurodegenerative disease. Institute Curie has recently acquired a state-of-the-art cryo microscope for cryo-tomography (A).
The aim of the internship is to understand the membrane deformation process induced by integrins, human membrane proteins involved in cell adhesion and migration. After activation, these proteins go through a recycling stage within the cells, which requires internalization of by invagination of the plasma membrane or endocytosis (B). We have designed an in vitro system with integrin to mimic the process of invagination (C). The student will have to acquire and analyze cryo-tomograms representative of snap-shots of membrane invagination, and determine the molecular and supramolecular organization of integrins at quasi-nanometric resolutions using advanced computational and deepl learning approaches (D). We are looking for a student with an interest in structural biology, imaging, computational analysis and interdisciplinary approaches. The student will initially be trained in cryo-microcopy and image analysis. She-He will then develop the project independently and with the help of team members and collaborators in cell biology (L. Johannes, Institut Curie) and applied mathematics (D. Castano-Diez, Bilbao).
- Beber, A., et al. Membrane reshaping by micrometric curvature sensitive septin filaments. Nat. Commun. 2019
- de la Mora, E., et al. Nanoscale architecture of a VAP-A-OSBP tethering complex at membrane contact sites. Nat. Commun. 2021
- Subra, M., et al. VAP-A intrinsically disordered regions enable versatile tethering at membrane contact sites. Dev. Cell. 2023.
- Shafaq-Zadah M, et al. Persistent cell migration and adhesion rely on retrograde transport of β(1) integrin. Nat Cell Biol. 2016
