Prof Ariel Ruiz i Altaba is Coordinator of the EU-funded research project HEALING, was founding director of the Swiss Stem Cell Network and is professor at the Department of Genetic Medicine and Development, Université de Genève, Switzerland. He is also an established visual artist. Emma Kemp met Ariel to hear more about science, art and how they might come together to build an understanding of the evolving world around us.
What is your scientific research all about?
In my lab, we’re trying to understand how cells communicate with each other to manage their behaviour or determine ‘cell fate’ – what a cell develops into as it matures: a skin cell, blood cell or something else. Cells communicate using substances they secrete, called signalling molecules. We’re interested in a particular signalling molecule called Hedgehog, and the set of other molecules and genes it is connected with in what is known as the Hedgehog-Gli signalling pathway. This signalling pathway can turn certain genes inside our cells on or off, or make them more or less active. We’re studying how this affects cells in normal situations such as maintenance of adult tissues and repair after injury; but we’re also looking at what happens when things go wrong. If you have too much of a signalling molecule that is normally tightly controlled, like Hedgehog, it can make certain genes very active and can cause problems like cancer. When the same genes are only moderately active, they can make our stem cells self-renew (copy themselves) in a controlled way, which is an important part of tissue maintenance.
"Studying this one signalling pathway is a very interesting way to look at the yin and yang, the balance of healthy tissue regeneration and cancer."
So the same cell signalling system is relevant to how things work in our healthy bodies, and to understanding disease?
That’s exactly right. The Hedgehog-Gli pathway involves several steps and molecules, all carefully balanced so that cells know what to do in normal development and in tissue maintenance or regeneration. But if this same pathway is corrupted – if the strength of the signal is inappropriate or the order of the events is wrong – you get cancer or other diseases. So studying this one signalling pathway is a very interesting way to look at the yin and yang, the balance of healthy tissue regeneration and cancer. We can look at regeneration as a process just like skin repair: a very controlled, precise mechanism to re-make what’s missing. Cancer goes beyond that – it makes what’s missing and then some more and some more and some more. And it doesn’t stop.
Our work has important consequences for human health. For instance, in the last two decades or so we have pioneered the role of Hedgehog signalling in cancer stem cells and sporadic human cancers (those that occur spontaneously, rather than being inherited from the parents). We were the first to show that Hedgehog signalling is involved in sporadic basal cell carcinoma (BCC), which is the most common tumor type, and the first anti-cancer drug that blocks Hedgehog signalling was approved this year as a BCC therapy. We have also pioneered the role of this signalling pathway in melanoma, prostate cancer, glioma and have defined its role in brain and colon cancer stem cells. One of our goals is to develop the most specific drugs to block Hedgehog signalling to destroy the stem cells of these and other cancers.
Naturally, the Hedgehog-Gli signalling pathway is not the only type of signal, it’s not the only language that cells use, and so one of the challenges for research is to learn how cells understand many, many messages and respond coherently by doing one thing or another. How do cells listen to what’s out there and then respond appropriately or, in the case of a disease, inappropriately? And how can different signals contribute to cancer and stem cell (mis)behaviour?
What first got you interested in learning how cells communicate?
I am really interested in how patterns form. My initial interest was in understanding how we develop. When I studied development in New York and Cambridge, I was interested in how the patterns are established that allow the embryo to form. Studying stem cells, regeneration, tissue maintenance and cancer really follows on from that because now I’m looking at how patterns are maintained and how they break down in disease. In a way, what we need to understand is, what are the signals that make tissue formation or regeneration happen and then stop at the appropriate times? And that’s anything but trivial. Of course, a single cell is going to have a hard time knowing what to do; it’s a group of cells that has to decide when enough is enough. And that’s one of my favourite problems; it’s the problem of pattern formation.
I’m basically interested in how things are the way they are and why they are not some other way. I’m also an artist, and here I’m interested in form and shape and meaning. It’s the same question viewed slightly differently.
"For me the greatest challenge in science consists in looking at all the things that everybody knows through different eyes."
If you consider art and science as different ways to view the same questions, do you think science is also creative?
Science can be as creative as the best creative art. Science is not just the scientific method, which is a way to make sure you don’t fool yourself, a way to make sure the data or observations you gather are independent of the observer. The exciting part of science is creative discovery. You should be prepared with the best training and have the best instruments for your voyage, but nobody can tell you what you’re going to find or where you’re going to go and that’s what’s exciting. Beyond the frontier of the known, there is no chartered method.
For me the greatest challenge in science consists in looking at all the things that everybody knows through different eyes. If I show you a picture of the latest asteroid to be discovered, it’s new and it’s exciting because nobody has seen it before. But I find it much more interesting if somebody teaches me something new about the moon, something that kills dogma, because that really makes you think and live differently. What drew me to science is that sense of mystery and freedom. That’s, I think, what drives creative thinking.
You’re an artist as well as a scientist. Which came first?
My mother is a painter and I was always surrounded by oil paints and turpentine, brushes and canvasses. So I guess my interest in art developed before my interest in science, but what developed first was an interest in the natural world. I was always fascinated about form. That took two parallel paths: one was to understand form scientifically, and therefore I became interested in pattern formation, how form comes about, how it’s maintained, how it’s deformed; and the other path was to try to develop an aesthetic language, an aesthetic view, even an intellectual or emotional approach to form and patterns. In art I am interested in issues of identity and understanding. How do we know what is what? How do we perceive identity? Many of the photographic series I’ve created have to do with different ways of seeing. For example, in my series, Embryonic Landscapes, which includes images of developing embryos, I show shapes, densities and textures as if I were sort of strolling through landscapes or making portraits. In another series, Biophilia, I use still lifes of common items, such as feathers, shells or bones, but showing only a little bit of the object in focus, with the rest lost in the shades of grey. The question is whether we think we know the whole by seeing only a tiny, tiny bit on the surface, a problem that resonates with racism, eugenics, colonialism, tolerance, etc... In another project, entitled Minimal Landscapes, I inquire about the meaning of boundaries and knowledge; the images show black islands and archipelagos in a white sea. All grays are condensed and yet the boundaries are porous: They are the seed of change − what separates us is what unites us. In Genome and Identity I ask, what is the genome and how does the genome identify us or not? In contrast to this deterministic possibility, Choices portrays the individual freedom and its inherent problems afforded by our thought. My art is about ways of portraying ideas and unresolved questions of identity and knowledge that I find challenging and current.
Have you got any advice for scientists or artists who want to understand more about the world around us?
Go into the subject matter. Delve into it. Spend time in it. There’s a lack of introspection at every level. In most cities I’ve been to, there are more people looking at their gadgets than at one another. Conversations seem to be at a minimum. Sometimes I think we have enough smart phones but not enough smart people. Take your time and think deeply about things. And trust your instincts.
Find out more
More about science and art by Ariel Ruiz i Altaba:
Related articles on EuroStemCell:
- Curing Parkinson's with Stem Cell Research? A research update from HEALING
- Cancer: a disease of stem cells?
Images copyright Ariel Ruiz i Altaba, reproduced with permission. For further information and galleries, visit the Ariel Ruiz i Altaba studio website.