 So the nanomaterials that we use are basically just very very small materials so liposomes are small fat-based molecules They're kind of like the cell membrane of a cell in that they've got kind of like a bi layer So two layers of fat molecules that you can put stuff on the inside of or you can stick stuff on the outside of So the liposomes that get used in the clinic carry cancer treating drugs It means it stays in the circulation of the blood for longer So it gives the drug more of a chance to get to where it needs to go and treat the disease because Currently if you just put the drug in it can often be excreted quite quickly from the body So I work on the brain the brain is notoriously difficult to get drugs into because of the thing called the blood brain barrier Which stops drugs and molecules getting through so we actually directly inject into the brain and What's good about the nanomaterials there is that they stay where you put them So if we inject into a very small area in the brain It doesn't start to spread the drug everywhere and the brain it keeps it where we want it to be So in this way you can stop negative side effects what I primarily work on is Parkinson's disease So for Parkinson's disease we use a rat model So we bring in rats and that are completely normal we get them in from the company and we can Give them Parkinson's disease by just injecting a toxin into the brain Which can have an effect on the brain that essentially mimics the symptoms of Parkinson's disease in the animal So to do this we anesthetize the animal will shave a little patch of hair off the top of his head So we can get access to the skull and we create a small hole in the skull through which we pass a very very thin needle Into the brain and the brain itself doesn't have any nerves for sensing pain So this part of the procedure isn't painful for the animal So it's not like when you get an injection through your skin mice and rats are prey animals, so they don't tend to Shout out to the world that they're in pain like maybe we would if you know you pop your toe So they tend to try and keep quite quiet and they don't squeak about it But we can tell by looking at their different features so often they'll like scrunch up their noses And their fur will bristle a bit and they'll tend to kind of hunch up in the corner They won't really want to be handled and if you open the lid of the cage They won't be kind of investigating what's going on. They tend to be a bit quite quiet Luckily with the surgery that I do with the animals We don't tend to have these symptoms afterwards in general just one injection of the painkiller at the end of the surgery Gets them through the bit just after surgery where there might be a bit Stressed and then after that they recover and they're usually eating and running around within an hour So they're happy out. We only give them Parkinson's in one half of their body So that means that the animal can eat can run around can groom his Caged mates as normal, but we can still see some behavioral outcomes in the animals that tell us whether he's got Parkinson's disease And then when we give them treatment that we're interested in we can follow up on his behavior and see if those symptoms Get better and see if he starts to go back to a more normal and behavior or if he stays with the Parkinson's symptoms So the rat model is in some ways very similar to the human model and a lot of ways very different So the biggest difference obviously being that humans wouldn't get Parkinson's in only one half of their body But one of the other things is that in humans, it's a slow progressive disease. So certain cells start to die We still don't know why these cells start to die, but they start to die in a very specific part of the brain This has kind of far-reaching effects within the brain that cause the slow progression of the symptoms that we see with Parkinson's disease and this tends to spread through different brain areas Whereas with the rats what we're doing is we're mimicking this but in a very quick fashion So we tend to kill the same cells, but in you know overnight So the rats will start to develop symptoms kind of within a day or two They'll already have the symptoms of Parkinson's disease So what this model isn't great for is telling us how the disease starts But the downstream symptoms of it are still quite similar to what we would see in humans in that they've got the Evidence of tremors. They've got this difficulty starting movements, which is one of the big problems with Parkinson's So when we're checking to see whether or not the animal has Parkinson's disease There's a couple of different behavioral tests that I use so one of the most widely used tests for Parkinson's is called a cylinder test So essentially you get a rat and you put them inside a glass cylinder And the natural behavior of a rat when you put them in a new environment is to stand up in his back legs and put his paws On the glass wall and have a sniff have a look around and see what's going on So when we do this we count them a number of times he uses his left paw or his right paw to balance himself and Then in that way we can count and see how much he's using those different paws When we give them the Parkinson's disease we inject the toxin into the right hand of their brain And they should lose a movement in their left side So at this stage what we generally see is that they don't use our left paw at all when for balancing themselves They only use a right paw a similar test which I think the rats quite enjoy is the cocoa pop test So we essentially put them in a little corridor with cocoa pops in cups on either side And we just let them walk up and down and eat as many cocoa pops as they want within say five minutes And we can count whether or not they're eating more cocoa pops from the right-hand side versus the left-hand side and Again after we give them the Parkinson's they should decrease the amount of cocoa pops they eat from their left-hand side So you'll see they'll walk up and down the corridor and they'll only pick food from the right-hand side And then they'll turn around and only pick food from the right-hand side again So again, it's quite a simple measure that gives us quite robust results in terms of whether or not they actually Have lost the use of their left-hand side So now we've got the model established for the animals that we can get rats that have Parkinson's disease This means we can start to try and deliver treatments into the brain So one area that we're particularly interested in is a small brain area that becomes very overactive during Parkinson's Which sounds quite counter-intuitive considering it's a loss of movement But actually this area becomes overactive and it kind of stops everything else from working correctly So what we want to do is get to this small area In humans use something called deep brain stimulation Which is an electrode that you put into this area you put out an electrical signal and it quietens down the area We want to see if there's a way that we can just inject something one time leave the brain take the needle out We don't have to leave an electrode in so it's less traumatic and in that way still quiet and down the same area So we're looking at gene therapies for doing this So instead of just being able to inject a gene therapy which the body would kind of degrade really quickly We're trying to stick it to the outside of our nanomaterials to see if it can protect it If you can keep it in the small brain area and stop it spreading around and then still see the desired effect that we're interested in