proteome dynamics and control of proteostasis
Each cell must keep millions of protein molecules properly functional and avoid accumulating damaged proteins. This condition, known as proteostasis, is achieved via balance of different activities like translation of new proteins, chaperone-mediated folding, post-translational modifications, elimination of non-functional proteins etc.. Distortion of this balance is detrimental. For example, some of the most socially impactful disorders - Alzheimer’s disease and Parkinson’s disease - stem from the proteostasis failure.
My group is interested in how cells control the functional state of proteins and maintain proteostasis. To answer these questions we are analysing protein dynamics - a “life record” of proteins within cells including when and how proteins fold, assemble into complexes, get modified and eliminated. By observing dynamics of proteins and protein complexes in normal cells and under conditions of proteostasis failure we aim to understand the mechanisms that govern proteostasis.
We are conducting our research primarily in budding yeast and applying a broad range of techniques including biochemistry, genetics and mathematical modeling. Although budding yeast is a unicellular organism, it is a well-established system to study proteins and protein complexes, and is extremely well-suited for biochemical and genetic work. The evolutionary conservation of the proteostasis control machinery also reassures that our results are relevant for a wider research community and for biomedical applications.
In the News
Dultz, E., Wojtynek, M., Medalia, O., and Onischenko, E. (2022). The Nuclear Pore Complex: Birth, Life, and Death of a Cellular Behemoth. Cells 11.
Kralt, A., Wojtynek, M., Fischer, J.S., Agote-Aran, A., Mancini, R., Dultz, E., Noor, E., Uliana, F., Tatarek-Nossol, M., Antonin, W., et al. (2022). An amphipathic helix in Brl1 is required for membrane fusion during nuclear pore complex biogenesis in <em>S. cerevisiae</em>. bioRxiv.
Onischenko, E.*, Noor, E.*, Fischer, J.*, Gillet, L., Wojtynek, M., Vallotton, P., and Weis, K. (2020). Maturation Kinetics of a Multiprotein Complex Revealed by Metabolic Labeling. Cell
Vallotton, P., Rajoo, S., Wojtynek, M., Onischenko, E., Kralt, A., Derrer, C.P., and Weis, K. (2019). Mapping the native organization of the yeast nuclear pore complex using nuclear radial intensity measurements. Proc Nat Acad Sci USA 116, 14606-14613.
Rajoo, S., Vallotton, P., Onischenko, E., and Weis, K. (2018). Stoichiometry and compositional plasticity of the yeast nuclear pore complex revealed by quantitative fluorescence microscopy. Proc Nat Acad Sci USA 115, E3969-E3977.
Onischenko, E., Tang, J.H., Andersen, K.R., Knockenhauer, K.E., Vallotton, P., Derrer, C.P., Kralt, A., Mugler, C.F., Chan, L.Y., Schwartz, T.U., et al. (2017). Natively Unfolded FG Repeats Stabilize the Structure of the Nuclear Pore Complex. Cell 171, 904-917 e919.
Andersen, K.R.*, Onischenko, E.*, Tang, J.H., Kumar, P., Chen, J.Z., Ulrich, A., Liphardt, J.T., Weis, K., and Schwartz, T.U. (2013). Scaffold nucleoporins Nup188 and Nup192 share structural and functional properties with nuclear transport receptors. eLife 2, e00745.
Onischenko, E., and Weis, K. (2011). Nuclear pore complex-a coat specifically tailored for the nuclear envelope. Curr Opin Cell Biol 23, 293-301.
Onischenko, E., Stanton, L.H., Madrid, A.S., Kieselbach, T., and Weis, K. (2009). Role of the Ndc1 interaction network in yeast nuclear pore complex assembly and maintenance. J Cell Biol 185, 475-491.
Buch, C., Lindberg, R., Figueroa, R., Gudise, S., Onischenko, E., and Hallberg, E. (2009). An integral protein of the inner nuclear membrane localizes to the mitotic spindle in mammalian cells. J Cell Sci 122, 2100-2107.
Onischenko, E.A., Crafoord, E., and Hallberg, E. (2007). Phosphomimetic mutation of the mitotically phosphorylated serine 1880 compromises the interaction of the transmembrane nucleoporin gp210 with the nuclear pore complex. Exp Cell Res 313, 2744-2751.
Onischenko, E.A., Gubanova, N.V., Kiseleva, E.V., and Hallberg, E. (2005). Cdk1 and okadaic acid-sensitive phosphatases control assembly of nuclear pore complexes in Drosophila embryos. Mol Biol Cell 16, 5152-5162.
Onischenko, E.A., Gubanova, N.V., Kieselbach, T., Kiseleva, E.V., and Hallberg, E. (2004). Annulate lamellae play only a minor role in the storage of excess nucleoporins in Drosophila embryos. Traffic 5, 152-164.
L. Meltzers Høyskolefond 2021 – Smådriftsmidler (2021-2022)
Research Council of Norway: FRIPRO/Transformative Research Project (KARMA - an innovative method to analyze cellular fate of proteins and its application to probe the control of proteostasis) (2021-2026)
Master projects are available. For details please contact email@example.com