VIB science in groundbreaking DNA sequencing technology

23 July 2016
​A collaboration between VIB and Oxford Nanopore Technologies has led to the development of a new key element of state-of-the-art DNA sequencing tools. The lab of Han Remaut (VIB-Vrije Universiteit Brussels) conducted groundbreaking research on a pore protein, CsgG, that will be used used to sequence DNA more accurately and effectively. Oxford Nanopore worked with Remaut’s team to apply the results of the research to build ‘R9’, a nanopore with unprecedented properties in real-time, portable DNA sequencing devices.

Nanopore sequencing technology depends on small electrical currents that run through a narrow
protein pore, or small hole – a nanopore – through which strands of DNA are guided during the sequencing process. Han’s lab has discovered that CsgG pore proteins have a structural buildup that can generate superior quality data compared to other nanopore sensors. Since this discovery, Oxford Nanopore has been fine-tuning the structure of the nanopore with the end goal of integrating it into cutting-edge electronic sensing devices including MinION and PromethION. This collaboration has a positive impact on both parties, allowing VIB to expand the scope of its research and enabling Oxford Nanopore to build its offering of fast and portable sequencing solutions in labs and remote areas, which benefits the community, the economy and the world.

Han, what makes this collaboration so interesting?
Han: “It’s very satisfying to see our basic research have such an impact on new technologies. CsgGbased pores give a tremendous increase in sequencing accuracy and speed compared to available nanopores. We started with a different focus when we set out to investigate the structure of the CsgG pore, which had to do with understanding its role in an unusual protein secretion process in bacteria. Strikingly, we also discovered that its structure makes it perfect for nanopore sensing applications such as DNA sequencing. Working with Oxford Nanopore will give our team the opportunity to continue to study CsgG in even more detail.”

Imke, how has your work with Oxford Nanopore impacted the future research goals of the project?
Imke: “I initiated the single channel conductance experiments on CsgG to help us understand its pore properties. These experiments allowed us to form a plausible model of the protein secretion mechanism adopted by CsgG, and also hinted at the protein’s potential for nanopore sensing applications. Single channel current recordings can be tedious and time-consuming to set up. The MionION device that Oxford Nanopore technologies developed for its nanopore DNA sequencing applications allows the parallel read-out of hundreds of channels at a time. Through this collaboration we can now address fundamental questions about substrate recognition and transport by CsgG that would not have been practically feasible using more classical electrophysiology setups.”

Publication
Goyal et al, Nature 2014


Research


Han Remaut and Imke Van den Broeck (VIB-VUB)