Visualization of the three-dimensional (3-D) organization of a eukaryotic cell, with its dynamic organelles, cytoskeletal structures, and distinct protein complexes in their native context, requires a non-invasive imaging technique of high resolution combined with a method of arresting cellular elements in their momentary state of function. We use state-of-the art electron microscopy techniques to study macromolecular assemblies and cytoskeletal elements, in situ.

Current Projects

1. The actin architecture in eukaryotic cells. Actin is required for cell motility, endocytosis and cytokinesis. These functions depend on the rapid assembly and disassembly of actin filaments controlled in time and space. Actin filaments in the cell cortex are linked to each other, hence forming a network anchored to the inner face of the plasma membrane. Polymerization and depolymerization, as well as crosslinkage and branching of actin filaments, are regulated by a multitude of proteins that act together in determining cell shape and motility. We study the 3D organization and remodeling of the cytoskeleton during fundamental biologically processes.

2. Dissecting the 3D structure of the nuclear pore complex. The sole gateways for molecular exchange between the cytoplasm and the nucleus are the nuclear pore complexes (NPCs). These large supramolecular assemblies mediate transport of biological cargoes into and out of the nucleus. Cryo-electron tomography is currently the method of choice for investigating the 3D structure of the NPC, as it allows the complex to be preserved in a close-to-native state.

3. Heavy metal nanoparticles. Localization of specific proteins, inhibitors or substrates within large biological assemblies is not yet a straightforward undertaking, due to limited resolution of 3D density maps and the dynamic properties of substrates within molecular machines. Therefore, specific molecular markers, such as heavy metal clusters, should be used in order to specify the location of the molecule of interest within a complex. We are synthesizing monolayer-protected nanoclusters with covalently-bound gold conjugate compounds and studying their potential use for identifying and localizing specific proteins within cells.

Recent Publications

Malka-Gibor, E., Kornreich, M., Laser-Azogui, A., Doron, O., Zingerman-Koladko, I., Harapin, J., Medalia, O. & Beck, R. Phosphorylation-Induced Mechanical Regulation of Intrinsically Disordered Neurofilament Proteins. Biophys. J. 112, 892-900 (2017). PMID: 28297648.

Turgay, Y., Eibauer, M., Goldman, AE., Shimi, T., Khayat, M., Ben-Harush, K., Dubrovsky-Gaupp, A., Sapra, KT., Goldman, RD. & Medalia, O. The molecular architecture of lamins in somatic cells. Nature 543, 261-264 (2017). PMID: 28241138.

Irobalieva, RN., Martins, B. & Medalia, O. Cellular structural biology as revealed by cryo-electron tomography. J. Cell. Sci. 129, 469-76 (2016). PMID: 26787742.

Tamir, A., Sorrentino, S., Motahedeh, S., Shai, E., Dubrovsky, A., Dahan, I., Eibauer, M., Studt, JD., Tanuj Sapra, K., Varon, D. & Medalia, O. The macromolecular architecture of platelet-derived microparticles. J. Struct. Biol. (J. Struct. Biol. 193, 181-7 (2016). PMID: 26767592.

Zingerman-Koladko, I., Khayat, M., Harapin, J., Shoseyov, O., Gruenbaum, Y., Salman, A., Medalia, O. & Ben-Harush, K. The assembly of C. elegans

Ph.D. Weizmann Institute of Science, 2002