Characterization of drug-induced ribosome biogenesis stress
Ribosome biogenesis (RiBi) is the result of a series of coordinated steps that occur in the nucleolus, where ribosomal genes are transcribed by RNA polymerase I to produce the 47S RNA precursor, which subsequently will generate mature ribosomes. Cancer cells have a higher ribosome requirement and therefore often present an increased sensitivity to RiBi stress. Hence, there is a growing interest in identifying and characterize compounds capable of inducing RiBi stress to use as antineoplastic therapy. The current project seeks to characterize how cells respond to drug-induced RiBi stress using a variety of techniques such as fluorescent microscopy, cell culture, immunoblot analysis, RT-qPCR, RNA interference, and approved and experimental compounds, among others. The study will include the assessment of nucleolar/nuclear proteins, nucleolar structure, cell cycle, p53 pathway, ubiquitin-proteasome pathway, DNA damage response and other emerging mechanisms. The Genome Integrity lab lead by Professor Jiri Bartek consists of experimental biologists with a broad range of expertise, working on nucleolar biology, cell cycle and DNA damage response. We are continuously looking for motivated students to master theses in the lab and learn current techniques in cell and molecular biology. |