Master’s Thesis ; Ogris lab

Overview

Discovery and characterization of new regulators of PP2A like phosphatases

The Ogris Lab is dedicated to uncovering evolutionary conserved mechanisms involved in the assembly, the activation and regulation of Protein Phosphatase 2A like phosphatases (PP2A, PP4 and PP6). We are currently seeking a talented and motivated Master''s student to join us in a project aimed at understanding the mechanism that protects these phosphatases from oxidative damage.

Assembly and activation of the PP2A family phosphatases - PP2A, PP4, and PP6 - are orchestrated by a set of common regulators, including alpha4, PTPA, TIPRL, LCMT1, and PME
1. Recently, we characterized a novel factor, Irc
21 (the yeast homologue of mammalian CYB5R4), whose absence strongly reduces the catalytic activity of PP4 and PP6, but not PP2A. Intriguingly, the deletion of Irc
21 can be rescued by expression of the conserved heme-binding domain of mammalian CYB5R4, revealing an evolutionarily conserved mechanism of PP4/PP6 regulation. Purified PP4 and PP6 can also be activated in vitro by ascorbate, a potent reducing agent. Our observation that PP2A activity is neither dependent on Irc
21 function nor on the presence of ascorbate points to a difference among these phosphatases in their sensitivity to oxidation and raises the question of the mechanism underlying PP2A''s increased oxidative stress resistance.

The main goal of this project is to decipher the molecular mechanisms that confer increased resistance of PP2A to oxidative stress. Within the framework of this project, you will gain expertise in the following techniques: yeast cell culture and genetic manipulation, various cloning techniques, Western blotting, immunoprecipitation, enzymatic assays, and protein purification (FPLC).

• Work on the assembly and activation of PP2A family phosphatases (PP2A, PP4, PP6) and study regulatory mechanisms that affect oxidative stress resistance.
• Gain hands-on experience with yeast cell culture and genetic manipulation, cloning techniques, Western blotting, immunoprecipitation, enzymatic assays, and protein purification (FPLC).
• Collaborate with lab members to plan, execute, and interpret experiments; contribute to data analysis and reporting in the Master''s thesis.

The Master’s thesis will be carried out in the Ogris Lab at the Max Perutz Labs. The start date is preferably May 2026 for the duration of 10-12 months. The student will receive a stipend of about €550,- per month.