Lab focus: Systematic investigation of the specificity of degradation pathways withimplication to human disease. Protein degradation plays a key role in nearly all cellular functions and failure to maintain protein homeostasis (proteostasis) has been shown to facilitate the manifestation or progression of a variety of pathological disorders, including inflammation, neurodegeneration and cancer.To establish a systems level understanding of the specificity of mammalian degradation pathways, we developed a genome-wide approach to characterize sequences promoting protein turnover and match them with the degradation mechanisms regulating them (Koren et al., 2018, Timms et al., 2019).
In our lab we use genetics (CRISPR screens) coupled with synthetic biology (high density oligonucleotide libraries synthesis), biochemistry, cell biology and systems biology approaches to obtain a global view of degradation pathways and to tackle open questions in the protein degradation field.
- Investigate how the degradation machineries of the cell specifically recognize and target substrates
- Characterize protein quality control pathways activated by cells to maintain proteostasis
- Explore the involvement of specific degradation machineries in various biological processes including receptor trafficking and turnover, organelle protein targeting, antigen presentation and more
- Elucidate how defects in protein degradation mechanisms result in disease such as cancer or neurodegeneration
Koren, I., Timms, R.T., Kula, T., Xu, Q., Li, M.Z., and Elledge, S.J. (2018). The Eukaryotic Proteome Is Shaped by E3 Ubiquitin Ligases Targeting C-Terminal Degrons. Cell 173,1622-1635.e14.
Timms, R.T., Zhang, Z., Rhee, D.Y., Harper, J.W., Koren, I., and Elledge, S.J. (2019). A glycine-specific N-degron pathway mediates the quality control of protein Nmyristoylation. Science (80-. ). 364.
We are looking for talented, curious and motivated post doctoral fellows with experimental and/or computational expertise to join us.
Applicants should send their CV and a brief description of their interests to Itay Koren.
Mailing address: The Mina and Everard Goodman Faculty of Life Sciences Bar-Ilan University, Nanotechnology and Advanced Materials Building (206), Rooms C765(office), C-767(lab), Ramat Gan, Israel, 5290002