Wednesday 28, June 2017

Interview with Prof Sara Brown

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Earlier this year we met with Professor Sara Brown, who we have partnered with for our Atopic Art project. We wanted to speak to her about how her research is progressing and why she is interested in working with artists. Sara spoke about the ups and downs researchers face doing the work that they do, ‘Some people think labs are sort of concentrated hard work, and they are, but I describe it as a roller-coaster, because some days you get really exciting discoveries… but there can be really disappointing, stressful and discouraging times as well’.

Sara’s work spans across both lab work and her clinics at Ninewells Hospital. She explained what motivates her to further the research and understanding of eczema ‘When I work in clinic I see how eczema affects the lives of children & families & adults … and people sometimes say, you changed my life because you sorted out my eczema! … that is a huge encouragement to work hard at research, to change more lives, because at the moment there’s so much we don’t understand about atopic eczema and we can’t always get the disease properly under control with the current treatments.’

As we get ready to launch our new Atopic Art micro-residency in partnership with Sara, her lab and her clinics, she also spoke about what drives her to open up her research and practice to artists: ‘I think the opportunity to have artists coming into the lab and observing the way scientists work offers an opportunity to express that work better to people outside science. In the residency I think the most important thing will be that the artists do what they want to do… and do what really inspires and excites them’.

If you are interested in applying for this new Micro-Residency check out our Open Call page for selection criteria, application guidelines, application form and details on how to apply.

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What motivates you to do your research?

My main motivation is to understand what causes atopic (allergic-type) eczema with the ultimate aim of improving treatment. I use genetics to investigate eczema because we know it runs in families. It’s very strongly inherited, so if you are an identical twin with eczema you’ve got about a seventy percent chance of having eczema yourself. The other reason to study genetics is to understand the real cause of eczema because at the moment the treatments that we have – greasy moisturisers (emollients) and steroid creams or ointments – are mostly treating the downstream effects of eczema, like dry skin and inflammation, rather than getting at the root cause. If we can understand how a person’s DNA makes them more at risk of getting eczema, we could eventually develop much better, more targeted treatments. So that’s my overall, long-term dream.

What is the current understanding of what causes eczema?

Eczema is called a ‘complex trait’ because it’s caused by a combination of effects from many different genes that interact with many environmental factors. Having said that, there is one gene that stands out as having a very strong effect on eczema risk. It was discovered in 2006 as a result of work done by a team at the University of Dundee: this gene holds the code for a protein called filaggrin, in the outer layer of skin. Filaggrin ensures that the skin forms a good protective barrier. Skin must keep what should be inside your body inside (blood, water, proteins etc). But also everything that’s outside your body needs to stay outside, so all the germs, allergens and irritants that might upset your body.

 
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The work that was done in Dundee, by Professor Irwin McLean’s lab, showed that changes like spelling mistakes in the filaggrin gene can mean that you don’t have enough filaggrin in your skin, and the barrier is leaky. This is what really increases your risk of getting eczema – by about 300 percent! This finding, in 2006, totally changed our understanding of eczema, putting a new emphasis on understanding the skin as a protective barrier against inflammation and allergy.

Now when we (dermatologists) talk to our patients, we can explain how skin is an important barrier to encourage people to use moisturisers, because using moisturisers can be inconvenient, sticky and greasy and often unpopular. I find it helpful to explain the reason for using a greasy moisturiser, it helps people realise that it’s worthwhile. So that’s filaggrin; it was a big breakthrough in understanding the genetics of eczema, but still less that half of patients with eczema have a problem with their filaggrin … meaning that for the majority of eczema patients we still don’t really know the genetic causes. That is what I’m working on now, trying to find other genes that cause eczema and then to figure out how they cause it, to move towards that ultimate goal of developing better treatments.

Can you give me a sense about what happens in your lab on a day to day basis?

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Yes, a big part of our work at the moment is growing artificial skin in the lab. I’ve got two people in my team who work full time in the lab; I’m there some days and other days I’m in the clinic but these two skilled scientists are there all the time. We get skin samples from our hospital: patients regularly undergo surgical procedures, having skin removed for medical reasons, so that skin is basically healthy skin but it’s not required anymore. Normally this skin would be thrown away, but through the Tayside Bio-Repository, trained nurses are able to ask the patients whether the skin removed during surgery can be saved and used for research. Thankfully many patients agree, and then the skin is collected, catalogued, and brought to my lab.
 

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When the skin arrives in the lab, it’s just a lump in a bucket, pretty unattractive! We carefully trim the tissue and use chemicals to harvest the cells out of the skin. Cells from the epidermis (the outer layer of skin) are separated from cells in the dermis (the inner layer of skin), and then we grow the cells in small flat flasks with pink liquid in them. The pink liquid has everything that the cells need to grow, and you have to keep them at the right temperature, with the right amount of oxygen and carbon dioxide, to encourage the cells to grow. Whenever we get cells from skin we get millions and millions of cells, so we divide the sample, catalogue and store some in a very cold freezer.at minus eighty degrees. Then the cells go into suspended animation.

To make the harvested cells into skin is we take them out of the freezer and let them start growing. We make an artificial ‘dermis’ (the inner layer of skin) by making a jelly with the cells from the dermis, with chemicals that are similar to the fibres in the inner layer of your skin. We grow the ‘dermis’ in small wells on plastic plates, and when it’s ready we pour the cells that are from the surface of the skin to the make the outer layer or ‘epidermis’ on top. We leave the new epidermis for one-two days for the cells to settle down and start to multiply happily. Then after one-two days we lift them out of the pink liquid up into the air, so the top layer of the artificial skin is now in air and the under layer is still in the pink liquid. It’s quite a fiddly procedure, you can imagine if the jelly breaks or it flips over, so you need to lift it very carefully.

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When skin cells are swishing around in a liquid medium they don’t grow proper skin, but as soon as they hit the air it’s a stimulus to them to try and make proper skin. They grow into layers that look like real skin. This whole process, from the skin arriving from the hospital into our lab, to us having little samples of skin that we’ve grown, takes two-three weeks.

You might wonder why we bother to grow our own skin samples, when we could use skin directly from the hospital? The reason we go to all the bother of growing artificial skin is because in the process of culturing these cells we can turn on or turn off genes that we think might be important in eczema. The experiments we’re doing at the moment are based on genes identified from research studies that have looked at sequences of DNA in thousands of people with eczema. We have chosen to switch off one specific gene in our skin samples to test whether it is really important in eczema. We do this by comparing the skin samples that we have grown: a skin sample with the gene switched off compared to a skin sample in which the gene isn’t switched off – to see if it makes any difference.

Do you see massive differences between the skin that is produced from the switching on and off of genes?

Yes, that is the key question. We have looked at a few different genes and some genes don’t really show any change at all. So then you have to discard those, that’s kind of a dead end in the research. But there is one gene in particular that we are looking at, at the moment that does seem to show a big difference. Even looking at the artificial skin by eye, the skin that we’ve grown looks dry and it has a scaly surface. People with eczema would recognise it! Their skin is often dry and scaly on the surface and that’s what our skin looks like when we look at it, so that’s an exciting start. Then we looked at it under the microscope and under the microscope and you see changes that look like eczema.

 
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I told you at the beginning that the skin barrier function is very important in eczema. So the other way we can test the skin that we have grown is to see if it has made a good barrier. We test the barrier in two ways: We can paint a special dye on the surface of the skin and if the skin is leaky that dye leaks down into the skin. If the skin has made a good barrier, then it doesn’t leak down and we’ve been doing that with this gene that we’ve found. The second way we test the barrier is to measure how much water is evaporating from the skin surface, to see if it is dry like eczema skin.

Some people think labs are serious, concentrated hard work, and they are. But it’s also a roller-coaster, because some days you get really exciting discoveries. You know the first time you look down the microscope you see that the dye has leaked through, showing that the gene you chose seems to be important. It is really exciting, a butterflies-in-your-stomach moment. That’s the stage we’re at right now. BUT when you find an exciting discovery you just have to repeat it and repeat it and repeat it again. That’s science, to make sure that it wasn’t just a mistake, or a chance finding. We need to be certain of what we’ve found, and repeating experiments to be certain is not so exciting.

What do you think might be intriguing for an artist coming to work with you? Why do think your lab might be a rich environment for an artist?

Well, there are many beautiful things in the lab, there’re many interesting things to look at, and stimulating visual things I think. I mentioned to you about the pink media that we culture cells in, you know I hope you don’t think it’s boring but I think it’s beautiful! The different shaped flasks are beautiful, and the sights you get down a microscope. You can actually see the cells within the jelly, and as the skin forms the cells change shape from little circles, to blobs with ‘arms and legs’ and then the cells in the top surface layers change shape again to become totally flat. It produces this very complex structure and all of that I think is beautiful.

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Part of the reason I love working with artists is, as scientists we can sometimes be a bit introspective and shy, perhaps. I think the opportunity to have artists coming into the lab and observing the way scientists work offers an opportunity to explain the science as well as challenges of our work to people who wouldn’t otherwise experience medical research. Obviously not everyone can walk through a research lab, it has to be a very controlled environment so you can’t invite the general public in. But you can invite selected people – talented artists – who can then potentially express the experience to other people and share it in a powerful way.

I think the more science moves forward and especially now medical science, the more important it is that the general public should not be frightened of it, but share the joy and excitement and understanding. My work, because it’s so focussed on patients and skin, is quite emotive, and I think it’s important to share that emotion. It’s important that patients understand how much we value their contribution and how what matters to them matters to the scientists. It works both ways, we work hard on trying to understand eczema but we’re totally reliant on eczema patients to tell us what matters, to share their experiences with us. People who don’t have eczema also make an essential contribution to research by sharing their skin samples with us from the hospital. This is what motives me to work with artists, and invite them in to see what it’s really like.

Another aspect is that it’s a very challenging life being a scientist. I told you about the roller-coaster and it’s very exciting at times, but it can be really disappointing and stressful and discouraging at times as well. You can work for many weeks, months and even years and not make a breakthrough. Science as a career is quite challenging and uncertain; you have to be dedicated to continue working in this environment. It’s easy to see the glamour of being a forefront researcher but the challenging side is, I think, something that also needs to be understood. This could also be communicated in art, depending on what most interests the artist..

Can you tell me a bit more about your clinics and what do you think an artist might draw from this experience?

I am a consultant dermatologist in the NHS and I run clinics for people with skin diseases of all types. This includes adults, elderly people, right down to new born babies. But my special interest is eczema, so I do regular clinics dedicated to children with eczema and clinics for adults with eczema. One of the main questions I ask is “how does the eczema bother you?” This is to try and understand how it affects their daily life because as a doctor you want to solve problems. You can jump in and solve what you see are the problems, but you need to try and figure out what the patient’s own perspective on their problems are, and those can be very different for different people.
 

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Eczema clinics are very time consuming. In a general dermatology clinic I have only ten-fifteen minutes for each patient. You can’t really start to help a patient with atopic eczema in any meaningful way in ten minutes, so my eczema patients have half an hour – sometimes much longer – even though the clinic can then run behind time. The other thing, in a children’s clinic especially, is that you have to work as a team with the child’s parents or carers to recommend what’s best for each child. You know it’s almost a full time job caring for a child with severe eczema so I have to try and understand what is going to be realistically feasible within their daily life. I am very aware that patients and carers are desperate for easier-to-use treatments.

Skin really matters a lot, you don’t always realise this until it goes wrong. If you have never had a skin problem, or you have never experienced that kind of embarrassment or stigma or discomfort of having itching, or spotty or bleeding skin then meeting patients can be a real eye opener. It’s a privilege for me to be able to help both now in clinic and in the future – hopefully – with better treatments.

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