Postdoc researcher in de novo design of transmembrane beta-barrels for nanopore sensing applications

Brussels VIB-VUB Center for Structural Biology

12 Sep 2021

Brussels

VIB-VUB Center for Structural Biology

Anastassia Vorobieva Lab

Post-doctoral

1

A fully-funded 2-years postdoc position is available at the laboratory of protein design at the VIB-Vrije Universiteit Brussel Center of Structural Biology, Belgium. The project is interdisciplinary (computational/wet lab work) and aims to design and test novel transmembrane beta-barrel pores using the Rosetta molecular modelling software.

The development of sensing and sequencing technologies using protein nanopores has resulted in high interest in protein forming pores through lipid membranes. Nanopore sensing technologies are based on the detection of current blockades induced by the passage of the analyte, and therefore requires high chemical and structural complementarity between the analyte and the channel. Re-engineering of naturally-occurring nanopores for the detection of analytes they have not evolved to transport has been challenging. The development of computational methods to design transmembrane channels specifically tailored to accommodate the analyte of interest is therefore highly desirable.

We recently developed new computational methods to design entirely from first principles transmembrane beta-barrels of 8-strands (Vorobieva et al., Science 2021). In this project, we aim to design nanopores with different beta-barrel architectures (10 to 14-strands) and experimentally test them for their capacity to insert into synthetic membranes and transport analytes of interest. The experimental characterization of the designed nanopores will be carried out in collaboration with Oxford Nanopore Technologies.

The tasks will include computational design of the beta-barrel proteins, production and purification from E. coli inclusion bodies, biophysical characterization in detergent micelles and synthetic lipid membranes and single-channel recording. The structure of the most promising nanopores will be determined using Cryo-electron microscopy (available on site).

Profile

Candidates should hold a PhD in Sciences (eg. Biochemistry, Biophysics) or Bio-engineering sciences and have a strong background in recombinant expression, purification and handling of membrane proteins in detergent micelles and synthetic lipid membranes. Experience in single-channel recording, python scripting and/or High Performance Computing is desired. The candidate should have a keen interest for protein design and an engineering-oriented mindset. Experience with research valorization and IP will be regarded as a plus.

How to apply?

Please apply online with a cover letter (in English) and your CV including and the contact information of 2 referees. For further information please contact the Dr. Anastassia Vorobieva (anastassia.vorobieva@vub.vib.be).