CSSB Seminar Series - OHAD MEDALIA
Abstract:
Lamins are nuclear intermediate filaments (IFs) of metazoan cells. They assemble into fibrous structures that are positioned between the inner nuclear membrane and the peripheral chromatin, although a small fraction of lamins is present in the nucleoplasm. Lamins are required to maintain nuclear structure and, together with many interaction partners, are involved in most nuclear activities. Mutations in lamins cause a group of >14 distinct diseases called laminopathies, it is not clear how lamins are organized in vivo and how these mutations affect lamin functions. Understanding how lamins are assembled, and how mutations in lamins and lamin binding proteins affect lamin filament assembly and cellular localization is essential for understanding the their modus operandi. Moreover, lamins are intimately interacting with chromatin.
Using variety of modalities, such as atomic force microscopy, molecular dynamics (MD) simulations, quotative fluorescence and cryo-electron microscopy, we provided unprecedented understanding of the remarkable structure and mechanical properties of nuclear Lamins. Using a set of cells expressing individual lamin isoform we show that lamin isoforms influence chromatin organization at the nuclear envelope. The results of this study indicate the unique mechanical and functional properties of lamins.
