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Dr Sheena Cruickshank

Dr Sheena Cruickshank is the academic lead for the public engagement of science at Manchester University.  As part of the Manchester Immunology Group, much of her work focuses on immunology and specifically infection and parasitology.  Her current research focuses on defining and developing biomarkers to help manage gut inflammation found in Inflammatory Bowel Disease.

So basically we evolved to have parasitic diseases

On earliest memories of science

Well, I come from a small town by the beach so I used to go rock pooling with my brother every single weekend and we had a tank at home and we used to bring various specimens back to the tank and look after them, and my sort of earliest memory is trying to keep a hermit crab alive through the process of it changing its shell, so we had to identify the right size shell.  We also had to get it out of the tank before the fish ate it, because as soon as the shell’s off it’s soft and it’s a target.  So, yeah, it really got me intrigued in science from kind of primary school onwards.

On entering into immunology

So, immunology is the study of the body’s defence system; so its basically how your body deals with infection. So that was…I think the reason I got into immunology is there was a lot of stuff in the news about AIDS, so it was kind of at the time - it shows you my age - when we were hearing a lot about AIDS and there was a personal family instance of cancer, and sort of seeing the sort of therapies being used about that, and I started to wonder why the immune system was turning against itself and why some people got sick and why others didn't and what was going on.  So I started to look into the topic of immunology as something that I would go on and study.

On the body fighting against itself

So, you've asked me what happens when the body starts fighting itself so I assume you're talking about autoimmunity, so, autoimmunity is where your body’s defence system does wrong, so it’s where your body starts reacting against itself.  So normally, what should happen is your immune system is trained to ignore everything that belongs to self, self-antigens, but in autoimmunity - and we don't know fully why - this goes wrong and your body starts reacting to itself, and because you can’t get rid of your own antigens you keep reacting, so you get what we call a chronic condition or long-term condition and that’s essentially where we’re at with autoimmunity.  And the reasons for that might be because you are genetically susceptible, it might be because you've had an infection that has a very similar appearance to a self-antigen or it might be because the things that regulate immunity, regulate tolerance, might have gone wrong, and that’s why you're reacting to yourself.

So if we’re talking about rheumatoid arthritis, that’s the most common autoimmune disease, so is this hereditary, well, partially yes; if you have family members with rheumatoid arthritis, you're more likely to get it.  You're also more likely to get it if you're female, so on the whole more females tend to get autoimmune diseases than males.  Presumably that’s because our immune system is set up slightly differently and it’s the action of our sex hormones.  But why you get it, we’re not really sure, it’s almost like a roll of the dice, you’ve got a few things that make you genetically more likely, plus some other circumstances that have gone wrong which kind combine together to give you that autoimmune disease.

On current research

Well, what we’re specifically doing in the lab at the moment…so this has really stemmed from an interest in parasite infection.  So for parasitic infection, some people do well with, say, a worm infection and are able to get rid of it and some people don’t, and they get what we call a long-term or chronic infection.  And when that happens and they get a gut infection, say tricuris, then they get something that looks very like inflammatory bowel disease, which is an autoimmune disease.  So by studying why people get susceptible to infection, we’ve been able to identify pathways that get switched on very, very early on in people that are going to be susceptible to infection, and these pathways also seem to be important in inflammatory bowel disease, so what we’re trying to do now is we’re looking at making something called biomarkers that will be used to better manage patients’ treatment with inflammatory bowel disease.  So these are little things that we can detect in the blood or the poo of patients with inflammatory bowel disease and that’s important because a lot of these patients have a long-term condition and they have what we call relapsing and fairing disease.  So if we can better manage the disease we can sort of prevent the damage that it causes.

On helpful parasites

So, basically, we evolved to have parasitic diseases; if you look back to the earliest human remains you can find evidence of parasitic infection, so essentially our immune system has adapted to have parasites in.  And most parasites, apart from the ones like the jewel wasp, they don’t want to kill their host so they have ways that they can sort of subvert the immune response.  So, for example, whip worm, the one that I mentioned earlier, Trichuris, that makes a secretory protein that can help dampen the immune response, and this one has been particularly investigated in terms of inflammatory bowel disease because we know that in the countries that got rid of worms have a lot of autoimmune diseases, but in countries that still have worms we don’t have a lot of autoimmune diseases so we think there’s some kind of link there.  So now this is being looked at in clinical trials and we’re also looking in more detail at the products that this parasite makes to try and understand how they affect immune cells, so that’s research going on in my lab and many other labs. The schistosome worm I just mentioned, it also makes lots of secretory proteins and lots of different antigens so that’s being investigated to see how that affects the immune system - a big paper just came out yesterday from the McDonald group at the University of Manchester - and how it affects cells.  So there are lots of positive sides to parasitic infection, it’s just I’m not sure that you necessarily want the parasite infection because parasites can make you very ill as well, so its understanding the manipulation that’s important. 

On hookworms

Yes, hookworms are another one that have been investigated; so hookworms have a somewhat unpleasant lifecycle.  So, these are tiny, tiny little parasites, they're about the size of an eyelash, and the eggs are in the soil and the eggs hatch so you've got little parasite larvae and when people…usually it’s when you're walking over the ground and basically the parasites will jump onto your skin and they can cause something called groundage ,so you can get a bit of a rash but generally you probably won’t notice.  They then migrate through the body and they make their way to the lungs where they start to get a little bit bigger, so they go through a few what we call larval moults.  Still very small. When they're ready, you cough them up then you swallow them again, and then they sit in your small intestine and they're little parasitic vampires, so they're there draining your blood, that’s basically what they're designed to do, but again they make lots of proteins to regulate the body’s immune response and there’s been lots of very interesting research about that. So people have used hookworm infection to try and treat allergy, and some people do it on the black market, and in Edinburgh there’s quite a lot of work trying to isolate the protein that the hookworm makes.

On future research

Is there one thing that we can unlock that will uncover everything? Well, probably, I think depending on which immunologist you ask you might get a different question and immunology is very, very complicated and it’s one of the most rapidly developing areas in science, I mean, we only discovered a new cell type, for example, a few years ago and there’s a lot of research going on to find out what that is.  But I think as a gut immunologist I’d say probably one of the most exciting and important areas would be the microbiome.  So the microbiome is your gut bacteria, it’s not the bacteria that lives in your gut, you do have bacteria living all over your body, but I’m more focused on the gut bacteria.  And this gut bacteria seems to do everything from training your immune system up, it helps you digest your food, it might even help keep you thin, it might even affect your behaviour, so I think understanding the microbiome and its relationship with the host could be one of the really, really important things in immunology and just science generally.

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