PP2A comprises a large family of trimeric holoenzymes, each of which consist of a catalytic C (PP2Ac), a structural A (PP2Aa) and a regulatory B-type subunit. PP2A dysfunction has been implicated in numerous cancer types, contributing to uncontrolled cell growth and tumor progression. Therefore, targeting PP2A activity holds promise as a potential therapeutic strategy for cancer treatment.
The assembly of PP2A trimers with tumor-suppressive functions is regulated by the reversible methylation of the PP2A catalytic subunit. Carboxyterminal methylation is catalyzed by the SAM-dependent methyltransferase LCMT-1, while demethylation is carried out by the PP2A methylesterase PME-1. Our most recent findings indicate that methionine starvation leads to the demethylation of PP2Ac, a process that can be partly rescued by a drug designed to restore the tumor-suppressive functions of PP2A. Understanding the mechanisms by which this small molecule interacts with PP2A and influences PP2A methylation and holoenzyme regulation are questions to be addressed in this project.
The project’s main goal is to create double and triple knock out cell lines of PP2A regulatory B-type subunits by CRISPR Cas9 and to analyze the response of these cell lines to the PP2A activating drug. In the frame of this project, you will gain expertise in the following techniques: mammalian tissue culture, DNA modification with CRISPR/Cas9, protein analysis methods like, western blotting, immunoprecipitation, quantitative western blot and immunofluorescence analysis.
The Master’s thesis will be carried out in the Ogris Lab at the Max Perutz Labs. The start date is preferably June 2024 for the duration of 10-12 months. The student will receive a stipend of about €518 per month.
Please send your CV and motivation letter to
egon.ogris@meduniwien.ac.at and ingrid.frohner@meduniwien.ac.at.
You can find more details on the research topics of the Ogris Lab page.
The evolution and development of mollusc shells
Unraveling the Complexity of Crossover Regulation in C. elegans
Dynamics of 3D Genome Structure and Function
How superworms can help to solve our plastic waste crisis
Title to be announced
New players in an old pathway: biology of methanogens of the TACK superphylum
Targeting a gerozyme to reverse muscle aging and increase healthspan
Shaping morphogen gradients: from molecules to tissues and back
Title to be announced
Studying stressed cells by in situ structural biology
The role of non-canonical double strand break repair pathways in genome stability and diversity
Exploring Microbial Resilience: Unravelling Escherichia coliand#x27;s Stress Response at the Level of Protein Synthesis
Arbuscular mycorrhiza development and function
Deep homology and deep diversity: Evolving genetic toolkits for making and sensing light
The evolution of cell type identity and tissue microecology at the fetal-maternal interface
The unanticipated roles of PICIs and phages in bacterial evolution
Chemical targeting of subcellular protein localization
Origin and diversification of gut-derived organs in chordates
Job's Dilemma for the Genome: Why Bad Things Happen to Good Chromosomes
Connections between carbon and nitrogen cycling in the ocean
Understanding how the DNA-loop-extruding protein complex Condensin folds a chromatinized genome into mitotic chromosomes
DrugMap: A quantitative pan-cancer analysis of cysteine ligandability
From Roads to Rivers? Occurrence and environmental fate of tire and road wear particles and of tire-related chemicals
FENS 2024 Satellite event: Home cage behavior monitoring at the interface of animal welfare and neuroscience
A mechanism for protein complex regulation at the mitochondrial surface
Striking physiology and cell biology of (marine) environmental microorganisms
Mechanisms controlling maintenance of cohesin dependent loops
Title to be announced