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).

Projects description:
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.

We:

• 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

References:
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.

Contact information
[email protected]
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
Phone: +972-3-7384211