/Computational Protein Design of Hybrid Nanopores for Biomolecular Sensing

Computational Protein Design of Hybrid Nanopores for Biomolecular Sensing

Leuven | More than two weeks ago

Explore the next generation of nanopore sensors at the intersection of bio- and nanotechnology.

Rapid and real-time sequencing of DNA and RNA with nanopores is a remarkable technology that found many uses in biotechnology, biomedicine and disease surveillance. Emerging nanopore based technologies aim to identify peptides, sequence proteins and polymers, and to detect metabolites and biomarkers. This PhD project addresses a key issue of the technology: the integration of the biopore with electronic devices. By designing new proteins that better interface solid-state nanopore technologies, we aim to enable the assembly of a dense array of individually readable nanometer-scaled protein nanopores on a sensor chip. Such a “hybrid nanopore” concept would open the door to next generation DNA and protein sequencing approaches, as well as the development of novel wearable devices and point-of-care technologies for the real-time identification of molecules and biomarkers.

The advantageous scalability and density of solid-state nanopore technology can be leveraged for the next generation of biosensors, but several issues still need to be addressed. These include the lack of sensitivity and the high variability of sensitivity of solid-state nanopores. A promising solution is offered by combining a biological nanopore with a solid-state nanopore into a hybrid nanopore, which aims to endow solid-state pores with the high sensitivity of biological nanopores. However, the present hybrid nanopore concepts are encumbered by the engineering at the interface of the biological and solid-state pores, resulting in leakages and misfits.

In this PhD computational protein design will be leveraged to develop versatile hybrid nanopores to tackle the present issues. The candidate will leverage state-of-the-art computational modelling tools to design novel proteins, based on the family of transmembrane beta-barrel (TMB) proteins. TMBs typically form stable and rigid pores through a lipid bilayer and are hence excellent potential scaffolds for the engineering of nanopore sensors and transmembrane channels. To find the best possible fit to solid-state pores, we will use de novo design and high-throughput experiments combined with cutting-edge semiconductor processing techniques and surface coating technologies such as organic self-assembled monolayers or inorganic atomic layer deposition.

This topic requires in-depth understanding of experiment and modeling. Diverse hands-on labwork (bio-chemistry, cleanroom, and electrical characterization labs) in addition to state-of-the-art molecular modeling research will be performed.

Imec is soliciting enthusiastic PhD candidates to advance single-molecule electrical sensing technology, approaching the problem both from the experimental and modeling side.

2025-127