A decade of discovery with MinION: insights from two pioneer researchers

As we celebrate a decade since the MinION Access Programme (MAP), we caught up with two pioneering researchers, who ‘thought it was crazy’ when MinION first came on the scene. Since then, Elizabeth Dinsdale and Robert Edwards have harnessed the power of nanopore technology for tremendous impact.

Read on to find out about their revolutionary research, from the potential of phage therapy to combat the global threat of antibiotic resistance, to leveraging the portable MinION device for marine conservation and in the fight against illegal wildlife trading.

'We thought it was crazy'

Liz Dinsdale and Rob Edwards (both professors at Flinders University in South Australia) were no strangers to sequencing when they tested out the MinION. Already experts in the sequencing space, they have been involved in sequencing 'for a very long time' – back to using radioactivity and polyacrylamide gels, and then being some of the very first adopters of next generation sequencing technologies for their metagenomics research. They knew that pore-based sequencing research was underway and were eagerly awaiting the chance to try it out, particularly to solve the problem of assembling bacterial and phage genomes thanks to its promise to deliver long reads.

'I think we thought it was crazy' Liz shared – going from devices so large to something that’s 'not much bigger than your phone…that was the most exciting part of it'.

For Rob, 'all sequencing technologies are a little bit crazy when you hear about them the first time, you’re like, there’s no way that could possibly work! And I think nanopore is included in that'. Yet 'it works right…the proof of the pudding and all that.'

One of Liz’s first uses of the MinION was was during a trip to Australia with 18 students. The students sampled microbial communities from the marine environment and carried out everything from DNA extraction through to nanopore sequencing and analysis. And this was all achieved in less than a week.

'These students went from having never sequenced anything, to being able to give us some information about the microbial community and some of the functional genes they had.'

Cutting-edge conservation in action

A highlight for Liz was a project from Shaili Johri, in her lab. She used nanopore technology to identify sharks and stingrays in the context of illegal harvest and trade (check out Shaili’s publication on this research here, and her talk at London Calling 2019). 'That was a really well received process.' Described in the National Geographic, this was a real breakthrough for conservation research, as well as for Shaili’s own career, resulting in collaborations with San Diego Zoo to investigate the genomics of northern white rhinos.

More recently the team have captured microbial genomes from the skin of white sharks in Australia, to identify what microbes are present. With the data from a single MinION run, they assembled complete microbial genomes 'which is really fabulous'. Michael Doane, a researcher from their group, is also using the MinION device to assemble a draft reference genome of the critically endangered grey nurse shark. The DNA is somewhat tricky to sequence due its secondary structure, yet this is a 'particularly interesting' discovery in itself that can really be explored when there is no limit to read length.

Revolutionising phage genomic research – from the bedroom to the bench

Rob’s team have been sequencing phages for several years using nanopore technology. Even during the pandemic 'we had the nanopore sequencer in our spare bedroom sequencing phage genomes ‘cause we could work at home' — a unique advantage of the portable MinION.

They were able to 'get basically one read that covers the whole phage genome from end to end'. With other sequencing technologies, they didn’t get the resolution needed because of the repetitive nature of phage genomes. They used to do hybrid sequencing, but now they only use nanopore on both their phage and bacterial genomes, partly because 'the accuracy has really kind of been solved with the new chemistries and pores'. He said 'now we’ve given up completely using short-read sequencing technology for those at all'.

Also, for Rob, the complexities of using alternative technologies and the price points have hindered their adoption by his group.

'Nanopore is really the first technology that’s delivered on that at a reasonable price point and [is] relatively straightforward and easy to use'

Accelerating phage therapy to combat antibiotic resistance

Rob’s group are currently interested in using phages as potential alternatives to antibiotics for targeting bacteria – an approach known as phage therapy. The threats of antibiotic overuse and the rise of antibiotic resistance are widely known. The World Health Organisation predicts that, by 2050, antibiotic resistant bacteria will be the global number one cause of death. An alternative way to fight antibiotic resistant bacteria could be using phages, which are great for killing antibiotic resistant bacteria, and do so in a strain specific way.

As Rob explained, these phages are isolated from the environment, such as from sewage, so it’s vital that the genomes are sequenced before being used for treatment. A lot of phages carry toxins, for example, which would be unacceptable to inject into a patient. Speed is essential in this context, to characterise the isolated phages accurately and rapidly prior to their use as treatment. Long reads are also needed to complete phage genome assemblies, allowing them to characterise all the genes present. Aligning to the unique benefits of nanopore technology, the group are exploring the potential of the platform in this area.

Making healthcare accessible for remote communities; tackling transport issues

Rob’s team are also looking at the potential of deploying nanopore sequencing in rural and remote communities for future healthcare. He explained how, for example, when people visit their doctor because of an infection, it’s impractical for the doctor to take a sample and then send it far away to a clinic for analysis — the time needed to receive those results back is 'just too long'. Whereas with MinION, this could be reported in 24 hours. There’s 'a really high demand' for a much more localised process.

Liz seconded the benefits of on-site sequencing with MinION. This means that local people can be directly involved in the sequencing of their wildlife, to understand genomics and build regional capacity. 'It would be a really important step forward' to be able to extract and sequence the DNA on-site, such as for shark species, most of which are CITES listed.

In situ sequencing also includes sequencing in-house, and Rob and Liz are both adamant that for their work, alternative long-read sequencing technologies with large device footprints are 'just not really in contention, because we can’t house that in-house'. To try and do something fast, 'that’s not going to work'.

What will the next ten years bring for genomics?

Looking to the future of nanopore technology, Rob suggests 'the real-time clinical applications, I think, are going to be really phenomenal as they come out and become more and more widespread…I think that’s going to really change how medicine is done'. He’s also hopeful about even greater throughput on the MinION, which could enable environmental sequencing 'like we haven’t seen before'.

From a wider perspective, Liz anticipates many advancements in human health, and is excited about the progression in genome technology or gene editing technology. She’s also interested in using genetics to rewild the microbiome of an animal that’s been part of a captive breeding program, prior to release back into the wild.

Although we cannot know for sure what the next ten years will bring for genomics, we are excited to see how users of nanopore technology will continue to embrace its full potential in their research.

For more information about the MinION and how it could enable you to answer your research questions, check out our products page, or head here to discover our celebratory 10 year promo packs!