 I'm joined here now on the Royal Society's sofa with Dr Chloe James from the University of Salford and Dr Heather Allison from the University of Liverpool. Welcome. Thank you. Now, tell me about your exhibit. It's all about the microbial Muppet Masters. Tell me more. Puppet Masters. So the Puppet Masters, this is what we're working with. These are bacteriophages. Okay. What's a bacteriophage? A bacteriophage is a virus, but it doesn't infect human or animal cells. It actually infects bacterial cells, and so they use these tail fibres to infect the bacteria that they're targeting, to recognise the molecules on the surface, and then they can infect them. And we're researching the different ways that they then can change the evolution of bacterial populations. So this is a big blown-up 3D printed version. How small would one of these be in real life? Yeah, this is absolutely massive. So normally this capsid head would be around about 50 nanometres in diameter. Wow, so really small. So yeah, incredibly small. So bacteria are about a millionth of a metre, and so phages are about 20 times smaller than that. So pretty tiny. So we've got some models of, so these are models of bacteria, in which case we need even tinier, oh well. These are still massive models of bacteria phages, and we've designed them to demonstrate some of the different ways that phages can affect bacteria. Okay, and what does this all have to do with us, really? Why do you want to study these bacteria phages? Well, I mean, bacteria phages are the most abundant organism on the planet. For every grain of sand, there's about a thousand bacteria phages. So there's billions and billions and billions of them, but there's a huge amount we don't know about them. In our particular research, we're interested in cystic fibrosis, and the lungs of people with cystic fibrosis are infected with, well, chronically infected with lots of different bacteria and fungi. And phages have quite an important role to play in that infection. There's a bit of a Jekyll and Hyde relationship, isn't there, in that some phages are being used as therapy to kill the bacteria. So that's a really exciting new treatment, particularly as lots of bacteria are becoming resistant to antibiotics. But the type of phages that we're really, really interested in actually put former partnership with the bacteria, and they can help the bacteria to adapt and survive longer in the cystic fibrosis lung. So the more we can try and understand how that works, then we can better understand how we can manage these infections. So hacking nature to kind of turn it against itself in a little way to conduct and cure these diseases. Talk to me about these other models that you've got. We've heard about bacteria phages looking at this. What's this one? So this is a model of the way in which we can use phages for phage therapy. So Glovy, you want to show them? Yeah, okay. So this is a bacterium. This is a phage. What you notice with these phages is that all the phages are different. They're incredibly diverse. So there's different colours. There's different shapes and sizes. So if I try to infect this bacterium, let's give a go with this one. The phage recognises molecules on the cell in a very specific way, and not every interaction with a phage is going to be productive. Do you want to try? It doesn't always work. Yes, okay. So I'm a little phage and I'm coming into my bacteria. I'm going to join to the surface. Nothing happened. Okay. Right, I'm going to try this one. Right, let's see. No, nothing happened. So this would be happening in the body, for example, right? They'd be coming along lots of different phages interacting with this bacteria. I feel like... You killed the cell! I killed the cell! Amazing! I'm looking at all the phages that you made. Okay, so we've reproduced phages using a bacterial cell. And then look identical to the phage that did the infection, and they're going to go on to kill other cells that look just like this one. So these will then go on and they'll meet another one and... So if this was causing the infection, all of its siblings are going to die as well. Okay, so what we want to do is to modify one of these so that it doesn't reproduce in that way. Is that right? Well, if you want to use it for therapy, you don't want to modify it at all. You want to harvest its ability to see the pathogen and let it do its thing. Gotcha. So we actually want to be helping these little guys do what they do and... Seek at its bacteria and let it do its thing. So how do you do that? So people can isolate phages from all over the place. The most common place is from sewage, and then you purify the phage out from there. The big challenge is, particularly in cystic fibrosis, there's been some big, good news stories recently where phage therapy has worked. But it's quite important to manage expectations for that, because as these models demonstrate, the phages are incredibly specific. So some phages that are able to kill a bacterial population in the lungs of one person might not work even if it's the same species. They might not work against the other bacteria in somebody else. So at the moment, it's really tantalising exciting therapy, but the technology is not quite there yet to sort of have this as a... It's never going to be a one-fit-all type of therapy. Okay, so does that mean that you would have to work with the individual patient and study their cells and what's going on in the bacteria in them in order to tackle it correctly and so that it's going to work for their body? Is that right? Potentially it'll have to be that specific, potentially. Yeah, so this is what we call personalised medicine. It's something that we're hearing quite a lot about now as the future of medicine and being able to target what we do to an individual patient. Is that ever going to be realistic in your work? It could be, we're not sure, but actually we want to get across the message that there are other types of phages as well. So we work with temperate phage. So if you remember earlier, I said sometimes phages form a partnership with their bacteria and can make the bacteria cause more severe disease. So we want to understand how that works as well. Have we got time to show you our second model quickly? Yes, please. So this is the second model that demonstrates that. So you're going to try and infect me now, aren't you? Well, not you personally, only your bacteria, because bacteria phages only infect bacteria. Yep. Right, so let you have a go. Yes, I'm excited about this. Right, so same thing again. Bacteria phage coming along to the bacteria interacting with it. No result. No result, fine. I'll let you have another go. Okay. Right, it's got a circle. Oh, here we go. Oh. Very good. Now that had a very different effect on the cell, didn't it? Yes. The cell actually grew. Ah, okay. So at the Summer Science Exhibition, we were referring to that as the acquisition of a superpower. I like it, tell me more. Okay, so this is the kind of thing that we're studying. Yep. So what's happened is during the phage infection, the genetic information inside the phage has been acquired by the host cell and it's entered into the chromosome of the bacteria. Now that could be anywhere, the bacteria cells acquired anywhere from 50 to about 250 genes. That's a lot of genetic information and it's been able to change the traits of the host cell. We don't actually understand a lot about the traits that have been altered and that's what we're studying. But it's this ability, my claw hand, it's this ability to manipulate the bacteria like a puppet master that gives the name of our exhibition and it's those traits that we're studying. So we've actually found one of the phages that we're studying that changes the rate at which the pathogen pseudomonas originosa isolated from the lung of a cystic fibrosis patient, the rate at which it can grow. So we know that this is one of the traits that is given by a single bacteria phage. Bacteria have been bombarded with phage for millions of years and they've kind of been in this evolutionary dance and they've so phages over the years have enabled pathogens to evolve and if we can understand more about that we can understand how to better manage the disease. So there's all this dark matter at the moment isn't there and we're trying to pull the curtains back on that and hopefully the ideal therapy is one that doesn't kill the bacteria but actually makes it less well adapted to the environment and less able to cause disease because then the sort of development of resistance will be slower because you're not actually trying to kill the bacterium. So that's like a real long-term plan but I think our part to play with that at the moment is to identify the function of those genes. So once you understand how these genes work you can then start trying to... We can target those traits. Yes. We can make those advantages less advantageous. Gotcha. So we've got a question in on Slido from Kate who asks will bacteria phages be the solution, the solution to the antibiotic crisis? Well that requires a crystal ball and I don't think any of us have a crystal ball but it's certainly one of the solutions that certainly many labs across the world are working on. Fantastic. I think antimicrobial resistance is such a global challenge and to tackle it then it needs to come from all sides from all kind of sectors of the community and there's lots of exciting new therapies coming along and I think phage therapy is one of them. Absolutely. Yeah, fantastic. And I think the UK is playing a big part in that as well. So some of the first clinical trials have occurred in the UK and I am very proud to say and be a part of the UK scientific community. Yeah well thank you for telling me all about your work. It's completely blown my mind. I knew nothing about this before but now I understand a lot more. So thank you so much for joining us today. Dr Chloe James and Heather Allison.