Building an army of MinIONs — Genetics Unzipped

May 23

May 23 Building an army of MinIONs

Click here to listen to the full podcast

What do you need to do if you want to gather an army of thousands of Minions? If you’re Gru – the antihero of the Despicable Me films – you just wait for them to show up. But if you’re a biotech company searching for the next big thing in DNA sequencing, unfortunately you have to do it the hard way.

The origin story of the MinION – a DNA sequencing device that fits in the palm of your hand – starts in 1989. At that time, the world of DNA sequencing ran on chemical reactions, either making or breaking DNA one basepair at a time, and highlighting the resulting letters with four fluorescent dyes – one for each of the bases, A, C, T and G. It was tedious and slow, and relied on having enough starting material to get enough fluorescent signal to read.

For several years, David Deamer at UC Santa Cruz and Harvard’s Daniel Branton had been dreaming of a completely new way of reading DNA, identifying each base in a single strand of DNA through its physical properties, in the same way a braille reader runs their finger along a string of raised bumps to read the letters on the page. But how could they do it?

They realised that the solution lay in pulling a single strand through a tiny hole in a membrane – known as a nanopore, bathed in each side with a salty solution that conducts electricity.

As each base pops through the hole, it should trigger a tiny electrical change across the membrane – not much, but enough to be detectable. And, importantly, each different base – A, C, T and G – should have its own characteristic electrical wobble, providing a readout of the sequence of a single strand of DNA.

At least, that was the idea. It took a while to prove the principle, and even longer to persuade anyone to believe it actually worked. For a start, such a pore didn’t exist. And there were huge technical challenges to be overcome in trying to persuade wriggling strands of DNA to feed themselves into the hole and proceed through in an orderly fashion, and to detect the signals as each base popped past.

George Church – who we spoke with in the last podcast – also came up with the idea of nanopore sequencing around the same time. He teamed up with Deamer and Branton to file for a patent on the idea, but lost interest and moved on to other sequencing technologies when the technical issues seemed insurmountable.

The other two kept going and nine years later, in 1996, they published a paper in the Proceedings of the National Academy of Sciences proving that it was possible to read the sequence of a strand of DNA pulled through a pore, and the field of nanopore sequencing was born.

By 2008, Oxford Nanopore – a company that spun out of Oxford University – had teamed up with Deamer and Branton to turn the concept into a reality. They showcased the first versions of their new commercial DNA sequencers – the tiny MinION and its big brother, the GridION – in 2012, gaining as much scepticism as excitement. Nice idea, sure, but was it any good?

The company put their money where their mouth was, offering MinION sequencers to anyone who wanted to try them, in exchange for a thousand dollar deposit. It was a smart move, and the scientific community put them to the test, taking them all over the world in search of things to sequence.

The technology has continued to develop over the years, particularly in terms accuracy, which was generally reputed to be not as good as larger, lab-based machines that run on more conventional fluorescence-based techniques.

One common application is plant genetics, where the MinION’s ability to read exceptionally long strands of DNA in a single stretch has proved very useful for unravelling the large, complex genomes of many plant species. In fact, there will even be one in action at the Genetics Society’s garden at the Royal Horticultural Society’s Chelsea Flower Show this year.

It’s fair to say that the MinION has been revolutionary in terms of bringing DNA sequencing to previously inaccessible parts of the world. They’ve been used for tracking infectious disease outbreaks, monitoring endangered populations of wild animals, citizen science projects and almost anything else you can imagine – a true global army of MinIONs!

So if you actually want a Minion Army that’s made up of those little yellow guys in blue dungarees, rather than a game-changing tiny DNA sequencer, all I have to say to you is BANANA!

References and further reading: