Monthly Archives: November 2017

Whipping up a storm

I’ve been out of the burble-sphere for a while as it’s been a busy term and I’ve been fully occupied with other things, principally two new projects that I’m setting up in school. One, a bee keeping club, is currently in the hive building stage and there’s nothing very exciting to report yet.

But the other is proving to be one of the most fun, interesting, challenging and exciting things I’ve been involved with at school…. and yet it nearly didn’t happen!

It started at a conference I went to in Birmingham last year. One of the other speakers described this amazing project where A-level students were doing original molecular research into Multiple Sclerosis. I was stunned. And immediately wanted to set up something similar. But despite attending the IRIS symposium at the Wellcome Trust HQ in London – amazing building – and finding a small group of students desperate to carry out this kind of research – we could not locate a single research group in Oxford who were interested in this kind of collaboration.

But then, at another conference this October – a school science conference in Tonbridge – I ran into Becky Parker again and she started enthusing about their Whipworm Genome project. I wasn’t immediately sold – it wasn’t the kind of hands-on, micro-pipetting/PCR-ing/gel electrophoresing/fluorescent visualising that I knew my students craved. Sitting in front of a computer scanning a genome for possible genes? I couldn’t see the appeal…

But she took my details, put me in touch with the head honcho at the Whipworm Genome HQ, and I signed up, thinking I might get 5 or 6 of the best Year 13 students interested.

Got that wrong.

I gave an assembly outlining this horrible Neglected Tropical Disease (neglected because only poor people get it, and who cares about them?). I described the project – bioinformatics/genomics – and what it would involve.

Whipworm Genome intro

Note the last slide – a screenshot from the Apollo software involved. I told them not to panic – it was as much a mystery to me as it was to them. I told them we would figure it out together, that I fully expected them to be teaching me, just as my 11 year old son schools me on how to play Clash of Clans….

And something struck a chord. A combination, I think, of:

  • genuine, original research – when they look at a whipworm gene, they are the first person to ever examine it
  • cutting edge technology – gene curating of whole organism genomes is Where It’s At…
  • a challenging and very steep learning curve (more on this in a mo!)
  • a worthwhile project – this might actually make a difference – it’s got immediate relevance
  • it’s online software, so you can do it anywhere you have a computer and internet access
  • looks good on CV/personal statement
  • immediately relevant to A-level…

Whatever it was, I currently have 86 girls signed up. I fully expect some of these to drop out, but not many. The interest and motivation is fantastic.

And it’s been a brilliant learning experience for me. I’ve never analysed a genome before, never curated a gene, never used the Apollo software. So having to do all that, whilst simultaneously trying to figure out how to teach it to students who currently don’t know a huge amount about DNA, has been hugely satisfying.

I started them off with a crash course on DNA

DNA intro for Whipworm Project

– the key bits for this project are understanding the concept of an anti-parallel 5′-3′ double helix; knowing about base pairs; knowing about introns and exons (or CDSs); knowing about UTRs (new to me!); knowing the identify of START codons and STOP codons; understanding that DNA gives rise to RNA which is translated into protein.

That’s a lot to take in for students who don’t know much about the basics of DNA!

But even being familiar with this doesn’t make the Apollo on-line software immediately accessible. So I had to practise with lots of examples and slowly build up a sense of how to do it, what to look for, how to trim or lengthen or adjust the computer gene predictions to what actually matches the evidence.

Because this is the really interesting bit. There are sequences that a computer has identified as looking a bit like a gene. But the computers often get it wrong. The student then has to compare the computer predictions to other data (principally RNA sequence data) derived from living whipworm cells, to see if the prediction matches what’s actually going on in real life…. and then adjust the predicted gene accordingly.

It’s fascinating, compelling and extraordinary. The power of the software, the sheer quantity of data, the elegance of the program, are all strongly addictive. At the moment, we’re just trying it out, running through a section on Chromosome 1 (whipworms have 3 chromosomes) for quality control issues. But just before Xmas, we should get our very own unique section of Whipworm Genome to annotate. Can’t wait!!!

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Origins

I’ve burbled on this topic before, but only briefly, tucking it at the end of a piece principally about World War 1 Shell Casings and the link to deadly diet drug, DNP…. I want to revisit it, primarily to describe in more detail the lesson, how I structure it, why it works, and use it as an example of how you can turn a non-practical lesson into a process of inquiry and discovery.

See what you think. Better still, let me know what you think!

Year 12. We’ve just about finished Cell Ultra-structure, they’re about to do a homework on Electron Microscopes. I show them this picture…

embryo

As ever, Powerpoint for me is a way of projecting thought-provoking images or interactive animations. I never use it to deliver notes – the phrase “Death by Powerpoint” exists for a reason…

So, what is this?

And immediately, they’re engaged. It’s a mystery! A puzzle! They’re all thinking and all have some kind of suggestion. I also use it as a way of encouraging involvement – have a go! what’s the worst thing that can happen? you might be wrong! but at least you tried…

After a round or two of interesting ideas, I start providing clues and someone usually guesses, correctly, that it’s a human embryo on the end of a pin.

I follow this up with another picture of a human embryo, just a bit closer in.

embryo 1

OK, key question, what did this start life as?

Yes, that’s right, a zygote. A single cell. Formed when a sperm and egg fuse…

But that egg, where did that come from?

From the mother. Of course.

And how did that individual start life? Yes, exactly, another zygote! Also formed from a sperm and an egg…

And that egg, where did that come from…?

We start a regress, back through the generation, through ma to grandma to great grandma and beyond.

If we keep going, I ask, where do we eventually get to?

To apes, someone say! Well, OK, yes, a common ancestor of us and apes to be strictly accurate, but no, much further… how far can you go?

They get it. The very first cell… This year, one of them can actually refer to LUCA (Last Universal Common Ancestor).

OK, all very cool and a bit mind boggling and stuff, but how would they describe that very very early cell, in just one word?

We try out a few suggestions before agreeing on “Simple”. This makes sense. Simple things evolve before complicated things. But what does that actually imply? What would this very early, very simple cell, have looked like?

We can’t know, of course, but as a way of stimulating discussion, I show them this:

bacterium.jpg

What do they notice about this cell, particularly compared to the cells they’ve been studying?

That’s right – it’s got no nucleus, no mitochondria, no rough endoplasmic reticulum, none of the complicated internal structures of the rat liver cell that has cropped up so frequently on their interpretive electron micrographs.

So if this isn’t LUCA, what is it? What very simple cells are still among us? Again, they generally get this – it’s a bacterium.

I then contrast it with a more familiar A-level cell…

plant cell

… from which they can cheerfully pick out half a dozen different clearly visible structures.

Which brings us neatly to the key question of the lesson. How did life on earth go from this…

bacterium

to this…

plant cell                           ?

At this point, I construct a time line on the board, starting with the origin of the Earth 4.5 billion years ago and sign posting it with the key relevant events along with the way (origin of life, 3.5 billion years ago, origin of complicated cells, 1.5 billion years ago, origin of modern humans, 200,000 years ago…). I then use this to add a few notes about the types of cell involved – the simple ones, the Prokaryotes, and what this means, and then the complicated ones, from which all multi-cellular life evolved, the Eukaryotes.

This allows us all to draw breath, before we return to the key question…

How?????

We bat a few ideas around. I drop a few visual hints (mainly be juxtaposing the two images and asking them what the bacterium resembles). And eventually someone has the necessary brainwave – did one of them start living inside the other?

Bingo! Endosymbiosis! Lynne Margulis’ brilliant idea that was, as things so often are, ridiculed and rejected….

Lynn Margulis and Endosymbiosis

And finally we can get on to the main exercise where I get them to figure it out for themselves (see attachment above). For if mitochondria used to be free-living bacteria, then perhaps we can make some predictions about what we might expect mitochondria to be like.

I put them into groups of 4 and get them to jot down all the things they already know about bacteria, without looking anything up in their books or their smartphones. Their list will eventually include at least some of the following…

  • they’re really small
  • they have plasmids
  • they reproduce through binary fission
  • they have ribosomes
  • we kill them with antibiotics

From this, I get them to come up with simple 5 predictions about mitochondria, again without looking anything up. Things like, “if mitochondria used to be bacteria, then they should have ribosomes…”

Once they have a list of 5, I let them check their predictions. And lo and behold, they’re right! There is evidence for endosymbiosis, even if it happened over a billion years ago. And they figured it out.

They’re convinced. They’re happy. It’s a successful lesson.

But now contrast it with an alternative lesson plan, perhaps put into a Powerpoint presentation… it might go something like…

“Today we are going to learn about endosymbiosis. Endosymbiosis is the theory that cell structures like mitochondria used to be free-living bacteria. Evidence for this theory comes in the similarities between the two. See the following list…”

It’s the self-evaluation every teacher should carry out before every single lesson plan – am I teaching? Or am I delivering information? The difference, at every level, could not be greater…