Gruenbaum Yosef

Country: Israel
Laboratory webpage
E-mail: gru@vms.huji.ac.il

Participation in Working Groups

  • WG1 - Biophysics of cell and tissue structure
  • WG2 - Structural analysis of biomolecules involved in mechanobiology
  • WG4 - Mechanobiological principles of rare and common diseases

Research Interests

My research mainly focuses on the structural organization of the cell nucleus and the nuclear envelope in health and disease states. We have made numerous contributions to this field, where we cloned the first invertebrate lamin and the first LEM-domain protein (otefin) and showed their roles in mitosis and nuclear organization. By using  the model organism of C. elegans, we have characterizrd lamin’s roles in maintaining nuclear shape, spacing NPCs and mitotic chromosome segregation. We suggested the gene expression model of laminopathies, established the model showing that the lamins, LEM domain proteins and BAF are all required to complete mitosis in a non-hierarchical (mutual) way and were the first to propose the way by which the nucleus, through SUN-domain and KASH domain proteins (the LINC complex), interacts with cytoplasmic structures. More recently, in collaboration with Dr. Ohad Medalia,we have determined the way that wild-type and disease-linked mutant lamin filament assemble in vitro and ex-vivo. In parallel, we have established C. elegans as a valid animal model to investigate laminopathies, and to test potential therapeutic drug candidates. We are currently ideveloped new methods to test the mechanical model for laminopathies and to establish the roles of lamins and ATX-2 as metabolic regultors.

Technologies offered to other EuroCellNet participants

These includes: 1) Genetics and cell biology of C. elegans. 2) Physicall techniques to test the response of C. elegans to mechanical strain. 3) Microscopy (fluorescence, confocal, EM). 4) Protein expression and purification. 5) Structural biology techniques. 

Technologies sought from other EuroCellNet participants

Single particle cryo-EM (medalia). Elastic analyses of cell nuclei (Buxboim). Cell cultures of patients or mice expression laminopathic diseases (Lattanzi, Bonne). 

Publications

Bar, D. Z., Charar, C., Yadid, T., Tafforeau, T., Lafontaine, D.L.J. and Gruenbaum, Y. Cell size and fat content of dietary restricted Caenorhabditis elegans are regulated by ATX-2, a novel mTOR repressor.  Proc. Natl. Acad. Sci. 113: E4620-4629 (2016).

Zuela, N. Zwerger, M. Levine, T., Medalia O. and Gruenbaum Y. A muscle-specific impaired mechanical response of an EDMD lamin mutation leads to motility phenotypes that are repaired by loss of prenylation. J. Cell Sci. 129:1781-1791 (2016).

Zingerman-Koladko, I., Khayat, M., Harapin, J., Shoseyov, O., Gruenbaum, Y and Medalia, O. The assembly of C. elegans lamins into macroscopic fibers. Journal Mechanical Behavior of Biomedical Materials. J Mech Behav Biomed Mater 63:35-43 (2016).

Zuela N. and Gruenbaum, Y. Matefin/SUN-1 Phosphorylation on Serine 43 Is Mediated by CDK-1 and Required for Its Localization to Centrosomes and Normal Mitosis in C. elegans Embryos. Cells 5, E8. (2016).

Zuela, N., Dorfman, J. and Gruenbaum Y. Global transcriptional changes caused by an EDMD mutation correlate to tissue specific disease phenotypes in C. elegans. Nucleus in press (2016).