Prof. Dr. Michael Sattler

Project description: The molecular mechanism of human peroxisomal protein import

This project aims to gain a deeper understanding of the functional mechanism of Grp94, the endoplasmic reticulum (ER) paralogue of the molecular chaperone Hsp90. Despite its importance in protein folding and quality control within the ER, both the structure and molecular mechanism of Grp94 remain poorly understood.

We will investigate the structural organization of Grp94 and its co-chaperones using an integrative structural biology approach that combines NMR spectroscopy, cryo-electron microscopy (cryo-EM), and small-angle X-ray scattering (SAXS). In parallel, biophysical and -chemical methods such as isothermal titration calorimetry (ITC), fluorescence polarization (FP), and folding assays will be used to investigate the binding of co-chaperones and small cofactors.

The student will contribute to the cloning of expression constructs, recombinant protein production, and purification, forming the foundation for the structural and functional studies. Through this work, we aim to uncover key aspects of the Grp94 functional cycle, providing insights that are fundamental for understanding ER proteostasis and may ultimately inform future drug discovery efforts targeting Grp94.

Project supervisor:  Sebastian Schindler

Required skills:

• Experience in a research lab is a plus, but not mandatory.
• Experience in laboratory courses (Chemistry, Biochemistry, Biology, or Physics)
• Basic understanding and knowledges of protein expression/purification and at least some of the biophysical methods listed in the project description.