Sequencing smoothies!

28 November 2016

Interview with

Kim Judge, Wellcome Trust Sanger Institute

The best way to look at life here on earth, is by reading the DNA code in an Green Smoothieorganism. Until recently this would have cost thousands of Pounds, and required a high tech lab. But new technology means that, now, almost anyone - including a school biology class - can sequence the string of DNA letters or "bases" that make up the genetic code inside a cell... including inside the fruits you throw into your morning smoothie. Kerstin Göpfrich went on a mission to get hers sequenced.

Just the strawberries and a banana  my love, yes?

Kerstin - Yes, please thanks.

I'm just going to weight the banana for you... £2.29 altogether. I'll put strawberries in a bag for you.

Kerstin - Mmm... delicious. But I should really save it for tomorrow because this drink is a scientific experiment. I will be visiting the Perse school in Cambridge and we will see if the students can find out what I put into my drink...

Student - I don't know... strawberries.

Student - Umm... lemon.

Student - I was going to say a banana. Some yogurt.

Student - Banana.

Student - A banana probably, yes.

Student - Yogurt probably.

Student - Blueberries.

Kerstin - Good guesses. But I wouldn't bet my money on them. With us in the classroom is scientist Kim Judge from the Wellcome Trust Sanger Institute. Maybe she can help out...

Kim - Maybe a good idea would be to sequence the DNA because each species of fruit will have a different DNA and we can use that to tell what's in the smoothie.

Kerstin - DNA sequencing means reading the letters of the genetic code, determining the order of the bases A, T, C and G. But first, we need to get the DNA out of the smoothie before we can sequence it, and you can do this at home. The students explain how:

Step 1 - Add dish soap...

Student - We add dish soap to destroy the membrane that surrounds the cell, which is like getting fat off dirty dishes.

Kerstin - Step 2 - Add salt...

Student - The DNA's still wrapped around little proteins so we have to add salt which binds the DNA and replaces the proteins.

Kerstin - Step 3 - Strain to remove solids...

Student - We sieved the smoothie mix that we had to remove any solids like seeds.

Kerstin - Step 4 - Add alcohol...

Student - We need to pick the DNA out. We do that by adding alcohol because it makes the DNA clump together.

Kerstin - And there we go. Clumps are swimming on my smoothie. They look...

Student - ... white and mushy.

Kerstin - That is DNA. Kim is fishing some of it out.

Kim - Wow, that's amazing, okay. What I've brought here with me in this tube is some magnetic beads. And the DNA will bind to these beads, and we can use that to exchange what solution the DNA is in.

Kerstin - That is step 5. Clean up the DNA and dissolve it in water. While we wait Kim is passing around the key bit of technology - the nanopore sequencer developed by Oxford Nanopore Technologies. It is a small hand-held device that plugs into a laptop like a USB stick. A nanopore is a tiny hole in a membrane, a million times smaller than the eye of a needle. How can it be used to sequence DNA?

Kim - In nanopore sequencing, DNA goes through a tiny hole and causes a characteristic disturbance in the current that flows across that hole and from that we can tell the sequence of the DNA. So DNA blocks part of the hole and that causes a different disturbance in the current depending upon what the sequence of the DNA is.

Kerstin - Is it going to work? I'm sceptical. One last step before we find out.

Step 6 - Heat the DNA to 37 and then to 70 degrees Celsius.

Student - So we're just warming it up to 37 degrees. Hence why I'm rubbing it... It's so we can prepare it for when we sequence the DNA.

Kim - What we're doing here is, just in the same way that you have to cook spaghetti before you eat it, we're transforming the DNA into a format that can be read by the nanopore. So that involves us breaking the DNA into sensible size fragments, and it involves us putting some additional fragments of DNA in. So that's going to direct the DNA to the nanopore and help to pull it through.

Kerstin - That means we are ready for step 7 - Sequence the DNA.

Student - You've put a solution of the DNA into the nanopore sequencer and that's going to transfer the data to the computer where it's going to be read.

Kerstin - The cool thing with this technology is that you can really see the data appearing in real time. As the DNA is pulled through the nanopore the computer is drawing the different current levels onto the screen, corresponding to different combinations of DNA bases. A bit like writing music where different levels correspond to different notes.

We may not be so pressed in time for our smoothie, but in the clinic this could really make a difference, Kim told me. The other big plus compared to competing sequencing technologies is that the device is portable. It is currently used to monitor the Zika epidemic in Brazil and by ecologists; present, and maybe future ones.

Student - I would go to the jungle because there's loads of animals there. Like loads of different species and you could just find their origins.

Kerstin - Sounds all very sensible. What does Kim think of my idea to sequence a smoothie?

Kim - For me, the easiest way to find out what's in a smoothie is maybe drink it and see what it tastes like. But it is going to be useful maybe if you're involved in checking food standards. There's no better way to be 100 percent certain about what someone's put in their smoothie than to check the DNA. It would also be a way you could check whether there was some bacterial contamination in the smoothie, maybe meaning that the smoothie's gone bad.

Kerstin - Lots of applications there. Does that mean we don't need lab sequencing centres any more?

Kim - Some of the other sequencing technologies have really strong benefits too. They're really good at sequencing lots of samples in one go and they're really accurate. Nanopore technology just has different pros and cons. It's a different part of the biologist's toolkit.

Kerstin - But back to our smoothie. Our DNA extraction was better than expected. Lots to sequence and more readings of DNA were still coming in. So Kim send us the results the next day. Pages of spreadsheets filled with the letters A, T, C, and G. A code that does not mean very much to me.

So, ready for step 8 - Decode the information...

Student - So once we've sequenced the DNA, we need to copy and paste that to an online database and you can use that to find out what was in the smoothie.

Kerstin - What was in the smoothie then?

Student - Fragaria ananassa and Musa acuminata. So we found out that in the smoothie there was banana and strawberry.

Kerstin - Mystery solved. We read an impressive total of ten million DNA bases. Back in 2000, that would have cost 100,000 dollars and we would have been in a big sequencing centre, not in a classroom. Quite impressive how the technology has evolved over the past decade.

Add a comment