PhD position: De Novo Design of Transmembrane Fluorescent Proteins

A fully-funded 4-years Ph.D. position is available at the laboratory of protein design at the VIB-Vrije Universiteit Brussel Center for Structural Biology, Belgium. The project is interdisciplinary (computational/experimental lab work). The broad aim is the design and experimental characterization of fluorescent membrane proteins using the Rosetta Molecular Modeling software.

The broad goal of our research group is to apply a de novo protein design approach to study membrane protein folding and function. By establishing a feedback loop between computational design and experimental validation, we aim to develop robust computational methods for the design of membrane proteins (MPs) with tailored properties and functions.

Green Fluorescent Protein, and later its engineered derivatives, have transformed biological research. A designer fluorescent protein folding in lipid membranes would find many applications as a reporter of super-organisation and biogenesis of biological membranes. This project builds on our previous experience designing fluorescent proteins (Dou & Vorobieva et al. , Nature 2018) and MPs (Vorobieva et al. , Science 2021), and aims to (i) develop computational methods for the de novo design of transmembrane β-barrels (TMBs) featuring a pocket tailored to bind a small-molecule and (ii) engineer the de novo designed proteins into transmembrane Fluorescence Activating Proteins (tmFAPs) that can be used as fluorescent probes in cellulo .

The tasks will include computational design, production, and purification from E. coli inclusion bodies, refolding in detergent, as well as biochemical, photophysical, and structural characterization of the designer membrane proteins. By the end of the thesis, super-resolution microscopy in cellulo is foreseen.

Candidates should hold a Master's in biochemistry, biophysics, or bioengineering sciences with a background in protein expression and purification. Preference will be given to candidates with previous experience with membrane protein purification and in vitro reconstitution. The candidates should have a keen interest in protein design and an engineering-oriented mindset. Although experience with protein modeling and design is not required, the candidates should demonstrate a strong motivation and commitment to learning python scripting, High-Performance Computing, and molecular modeling with Rosetta.

Please apply online with a cover letter (in English) and your CV including the contact information of 2 referees. For further information please contact Dr. Anastassia Vorobieva ([email protected] ).