PhD Position in Chaperone-Mediated Biogenesis and Activity Regulation of Protein Phosphatase-1
KU Leuven Laboratory of Biosignaling & Therapeutics
Belgium

Phd Position In Chaperone-Mediated Biogenesis And Activity Regulation Of Protein Phosphatase-1

 

The Laboratory of Biosignaling & Therapeutics investigates cellular signal transduction pathways at the molecular level. A major current goal is to

develop protein phosphatase PP1 as a target for novel cancer and neurodegeneration therapies.

Project

 

Research project

 

The synthesis of enzymes involves multiple, tightly regulated steps including transcription, translation, post-translational maturation, and the association of co-factors and regulatory subunits. Protein phosphatase-1 (PP1) is a very conserved and essential eukaryotic Ser/Thr phosphatase that functions as the catalytic subunit of at least 200 distinct holoenzymes. However, it is not understood how PP1 acquires its native conformation and catalytic-site metals. Neither is it known how PP1 forms holoenzymes through association with regulatory subunits that determine when and where the phosphatase acts.

 

 

We aim to explore the role of two ancient PP1-interacting proteins, i.e. Sds22 and Inhibitor-2, as chaperones that guide the biogenesis of PP1. We will determine the crystal structure of the PP1-Sds22 complex and generate antibodies that are specific for the Sds22-induced conformation of PP1. Also, specifically modified cell lines will be generated to study the role of Sds22 and Inhibitor-2 in the biogenesis and activity regulation of PP1. Additional regulators of PP1 biogenesis will be identified by trapping of immature forms of PP1 and by a novel technique that enables the tagging of proteins that interact with PP1/Sds22 or PP1/Inhibitor-2. In addition, we will use rabbit reticulocyte lysates to reconstitute the biogenesis of PP1. Collectively, these experiments are expected to generate key insights into the biogenesis and activity regulation of PP1.

 

 

References:

 

    Heroes et al., Structure (2018): pii:S0969-2126(18)30458-1. doi: 10.1016/j.str.2018.12.002.

    Weith et al., Mol Cell (2018): 72(4):766-777.e6. doi:10.1016/j.molcel.2018.09.020.

 

Profile

 

    You have a good background in basic sciences.

    You are willing to learn and adopt a variety of techniques of biochemistry, molecular biology and cell biology.

 

    You have excellent oral and written communication skills, and have a good knowledge of English.

    You aim for perfection and are practically skillful.

    You are ambitious, inventive and have a long-term vision.

    You are willing and capable to work as a team member.

 

Offer

 

    We offer a doctoral position for 4-5 years in a stimulating scientific environment.

    You will be registered in specific program of the doctoral school and will be able to attend the associated courses.

 

    You will have access to state-of-the-art research facilities.

    You will be guided on a daily basis by well-trained professionals and get a thorough training in scientific thinking, practice,presentation and writing.

 

 

 

Interested?

 

For more information please contact Prof. dr. Mathieu Bollen, tel.: +32 16 33 06 44, mail: mathieu.bollen@kuleuven.be.

 

To apply, please submit as soon as possible your motivation letter, CV, copies of transcripts/MSc degree, and names and contact information of at least two references.

You can apply for this job no later than July 31, 2019 via the online application tool

KU Leuven seeks to foster an environment where all talents can flourish, regardless of gender, age, cultural background, nationality or impairments. If you have any questions relating to accessibility or support, please contact us at diversiteit.HR@kuleuven.be.


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