Ph.D.: The Hebrew University of Jerusalem, Israel
Post-doctorate: National Institutes of Health, USA
Position: Senior Lecturer
Department of Life Sciences
Faculty of Natural Sciences
E-mail: elianat@post.bgu.ac.il
Cellular dynamics and macromolecular architecture in 3D
Cells are composed of many large, multi-molecular complexes executing distinct cellular functions in a confined space and operating in a dynamic, highly coordinated fashion. Understanding the kinetics and 3D organization of such protein complexes is, therefore, key to understanding cellular mechanisms. Recent advances in fluorescence light microscopy techniques now permit the dissection of the spatiotemporal behavior of proteins in their intact cellular environment. Confocal spinning disk microscopy provides the high imaging speed, high sensitivity and high dynamic range required to measure protein dynamics in cells, while structured illumination microscopy (SIM) is a fluorescence-based super-resolution imaging technique capable of three-dimensional (3D) multi-color imaging at 100 nm lateral and 350 nm axial resolution in any biological sample up to 10 microns in thickness. As such, SIM is one of the most suitable techniques for mapping the spatial organization of protein complexes in their native environment at nanometer scale resolution. The temporal information obtained by spinning disk microscopy and the detailed spatial information obtained by SIM can be integrated to generate a spatiotemporal map of protein complexes in a given cellular process. Constituting such spatiotemporal maps will facilitate mechanistic understanding of different cellular machineries.
1. Understanding ESCRT mechanism of action. The ESCRT complex is emerging as one of the major cellular machineries responsible for driving membrane fission in cells. Additionally, a fundamental role for the ESCRT machinery was recently defined in driving the very late events of cell division that lead to the physical separation of two daughter cells. We aim to elucidate the mechanism of action of the ESCRT machinery in driving membrane fission using mammalian cell division as a model system. We hope to do so using advanced quantitative imaging approaches, as well as by developing new tools for arresting the ESCRT pathway. As the ESCRT machinery is involved in numerous cellular functions, including receptor degradation, viral budding and cell division, our results will have applicative implications including for the development of drugs to block uncontrolled cell division, viral infectivity and other cellular processes.
2. Dissecting the spatiotemporal regulation of cytokinetic abscission. Cell division is one of the most regulated and coordinated processes in cell biology. While much is known about the temporal regulation of early division steps (prophase to anaphase), little is known about the temporal regulation of late division steps. Recent studies indicate that the final steps of cell division termed cytokinetic abscission are highly coordinated in time and space. However, the regulatory basis of this process, which terminates cell division giving rise to the formation of two independent daughter cells, is still unknown. By generating spatiotemporal maps of different cytokinetic proteins at different late stages cytokinesis we aim to elucidate the regulation of cytokinetic abscission and to determine the mechanistic basis for abscission timing.
Lee H.H., Elia N., Ghirlando R., Lippincott-Schwartz J. and Hurley J.H. (2008). Midbody targeting of the ESCRT machinery by a noncanonical coiled coil in CEP55. Science 322(5901):576-580.
Rambold A., Kostelecky B., Elia N. and Lippincott-Schwartz J. (2011). Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation. Proc. Natl. Acad. Sci. U.S.A 108(25):10190-10195.
Elia N., Sougrat R., Spurlin T.A., Hurley J.H. and Lippincott-Schwartz J. (2011). Dynamics of endosomal sorting complex required for transport (ESCRT) machinery during cytokinesis and its role in abscission. Proc. Natl. Acad. Sci. U.S.A 108(12):4846-4851. Ranked “must read” in Faculty of 1000.
Elia N., Fabrikant G., Kozlov M. and Lippincott-Schwartz J. (2012). Computational model of cytokinetic abscission driven by ESCRT III polymerization and remodeling. Biophysical J. 102(10):2309-2320. Selected for cover.
Fridman K., Mader A., Zwerger M., Elia N. and Medalia O. (2012). Advances in tomography: probing the molecular architecture of cells. Nat. Rev. Mol. Cell. Bio. 13(11):736-742.
Elia N.*, Ott C. and Lippincott-Schwartz J.* (2013). Incisive imaging and computation for cellular mysteries: lessons from abscission. Cell 155(6):1220-1231. *Corresponding authors
