Thesis supervisor: Zoltán Lipinszki
Location of studies (in Hungarian): Institute of Biochemistry, HAS-BRC, Lendület Laboratory of Cell Cycle Regulation Abbreviation of location of studies: SZBK
Description of the research topic:
The reproduction of cells is fundamental to the development and function of all living organisms. Therefore it must be tightly regulated and carried out with high fidelity and accuracy. The misregulation of cell division during the animal cell cycle results in serious developmental defects or cell proliferative diseases, such as cancer. Fundamental to screening for or correcting the resultant abnormalities in humans is defining their underlying molecular etiology. It is well established that besides many other postsynthetic modifications, kinase-mediated protein phosphorylation can serve as a molecular switch to fine-tune eukaryotic cell division. Key to the success of this regulatory mechanism is its reversibility; an antagonistic enzymatic activity driven by protein phosphatases. Despite this recognition, relatively little is known about how protein phosphatases govern cell division. Therefore we aim to comprehend the function of a group of PP2A-like Ser/Thr phosphatase holoenzymes that are essential to mitotic progression, but the molecular details are poorly understood. The major objective of this PhD project is the identification of phosphorylated mitotic substrates of the different PP2A-like phosphatases using AP-MS technique. Then, we will explore how dephosphorylation of the substrates contributes to cell division regulation by applying cell biological and classical genetic approaches. Finally, we wish to generate recombinant phosphatase complexes and establish dephosphorylation assays for in vitro purposes. We will utilise the Drosophila melanogaster model system, which recapitulates the phosphatase network observed in man but with the ability to integrate biochemical, cell biological, proteomic and genetic experimental approaches.
Required language skills: English B2 Recommended language skills (in Hungarian): Hungarian (not obligatory) Further requirements: Candidates should have a diploma in Biological sciences and must have advanced knowledge in using routine biochemical, genetic and molecular biological techniques. Candidates should be able to independently read, understand and write scientific paper