Claudio is searching for the keys to the genome

Growing up, Claudio Cantù had a strong passion for the natural world. This fascination eventually led him into the world of molecular biology. "My life goal mission is to understand how the genome works. Our genome determines what we are, yet we do not know or understand how most of it works!” 

Male researcher in university surrounding. Claudio Cantù is searching for the keys to the genome. Ulrik Svedin

When he is not in the lab trying to unlock doors to the genome, you might find Claudio doing lake marathons in the summer.

"Sport is a big component of my life. Almost an obsession of late. In the summer I do something that is called lake marathons. It means swimming in as many lakes as possible. An activity that I love doing", says Claudio.

 

Thriving in Sweden

It has been just over four years since Claudio Cantù arrived in Sweden. He left Switzerland and University of Zurich in 2018 and started his position at Linköping University (LiU). At that point in time, he had obtained a couple of offers, but the one from LiU was by far the best one.

"It was the best offer because of the WCMM initiative. The prestigious starting grant allowed me to do a lot of experiments and hire other scientists. What I liked about this university is that they made me feel wanted and that was most important for me. After four years I still feel very welcome."Image of all the members of the Cantù Lab.Members of The Cantù Lab. Photo credit Ulrik Svedin

Over the past couple of years at Linköping University a lot has happened. He is now managing a research group of ca. ten people in the Cantù Lab, where they study embryonic development. It essentially means what happens from the moment we are conceived until the moment we are fully functioning organisms. Claudio explains what the problem is that they are trying to solve.

"You are one cell in the beginning, and many trillion cells in the end. In our lab we try to understand what are the instructions of the genome that tell each cell what it must become. This is what keeps us busy every day."

My life goal mission is to understand how the genome works

 

Closed doors of the genome

The Genome contains all the genetic instructions to make a person. Every cell of our body (with just a few exceptions) has the same genome, which is the collection of all the ca. 20 000 genes that make us what we are. 

"My life goal mission is to understand how each cells activate the right genes, which is a problem far from trivial to solve", says Claudio.

If you sum up all the genes, you have somewhere between two to five percent of the genome. The rest of the genome are things that we don't understand very well. Claudio tries to describe it with the help of an analogy, in which you live in a house but do not know what there is behind most of the doors.

"You live in a house that has ten rooms, but you have only been in one of them. All the other doors are closed: are you not curious to go and open the other doors and see what there is in your own house? We have this type of knowledge of our genome, as we can only describe less than ten percent of its content. The genome contains the instructions to make a human being or any existing organism: can you think of a more important question? It took me 15 years to grasp that this is what keeps me up at night."

Several research groups all around the world are trying to open those doors, but it is a very challenging task. What Claudio and researchers in his field need to understand are molecular events on such a small scale that only sophisticated technologies could reveal. You cannot see the genome in action with your naked eyes, and the important details are not even visible with the most powerful microscope.

An image where a researcher examines in the lab.In the lab they study how cells regulate their gene expression during embryonic development, and how this leads to the formation of distinct cell types and organs. Photo credit John Karlsson"We often need to rely on a type of evidence that is indirect. For example, we can remove a gene or a segment of the genome and then observe what happens to the embryonic development of a mouse. If, for instance, the mouse doesn't develop the eye, we can conclude that that gene or genomic segment is required for making an eye. However, if you remove the engine of a car, the car stops working. Yet, this does not tell you how the engine works."

Technology is one of the main components required to opening more doors.

"We are not only trying to respond to specific questions, but we also try to develop new technologies that might be a key for those doors. Give us 20 years", Claudio says with a laugh.

 

Curiosity and beauty

There are three reasons why this kind of research is important according to Claudio.

"The first, as we discussed, we must discover what there is behind those doors. Curiosity is an unstoppable process that characterizes humanity, at the core of the desire of understanding things."

Claudio is hoping that his group can contribute to opening some of those doors. Then everyone can enter.

"This is one of the great things with science. Once we discover something, it can become common knowledge. Common in the sense that everyone can look at it, study it, check the evidence and try to disprove it. We all benefit of knowledge."

 

The results of science, like a beautiful artifact, are comparable to a Van Gogh painting

 

The second reason is what Claudio refers to as the Van Gogh principle.

"When we discover a new fact about the world, we realize how elegant the mechanisms of nature are. The results of science, like a beautiful artifact, are comparable to a Van Gogh painting, as they are human achievements in front of which one could feel awe, wonder and even a deep sense of spirituality."

The third is improving life quality, by allowing the discovery of the causes and treatments for disease.

"You might be surprised that I put this third, but I want to be honest. I am primarily motivated by curiosity, and by the impulse of understanding how complex life is."

Benefit to society

On how his research can be of benefit for society, he believes that the research on embryonic development has an impact.

"This might sound paradoxical, but by studying embryonic development we have also understood that some cells in adult bodies can reactivate embryonic genetic programs, and this can result from mutations caused by sunlight, smoking, bed food etc.. Often cancer cells look like the rapidly proliferating cells of an embryo."

What cells during embryonic development know very well to do is to grow, a lot. In a few weeks, from one cell an embryo becomes composed of many trillion cells.

Pierfrancesco Pagella, postdoctoral fellow, works in the lab with Pritha Guha Mojumder (center) and Valeria Ghezzi (left).Members of the Cantù Lab. Pierfrancesco Pagella, postdoctoral fellow, works in the lab with Pritha Guha Mojumder (center) and Valeria Ghezzi (left). Photo credit John Karlsson"If you reactivate some of those processes in the adult, even if you don't want to reactivate them, well, this is what we call cancer. Our discoveries already helped us identifying some instances in which cancers reactivate developmental embryological genetic processes. This is important because it might be these aberrantly activated processes might become the target for the notorious magic bullet."

The magic bullet refers to Paul Ehrlich (1854–1915) who coined the term. Ehrlich predicted that chemists in their laboratories would soon be able to produce substances that would seek out specific disease-causing agents. He called these substances “magic bullets.”

The big problem with cancer biology is that cancer arises from our cells. A cancer cell has our genome and is very similar to our cells. That makes it difficult to distinguish them from the normal cells of our bodies, which also need to proliferate.

"We might be on to something right now and this derives from our studies of embryonic development, which I think is fantastic."

 

Three rare moments

Having a breakthrough in the lab as a scientist is not something that happens very often. Claudio can recall three such rare moments. Once during his PhD, once during his postdoc and once in Linköping. Claudio Cantú talks passionately about his research in front of his bookshelf where we can see the Docent diploma from 2020.Claudio Cantù talks passionately about his research in front of his bookshelf where we can see the Docent diploma from 2020. Photo credit John Karlsson

"I can recall three different moments throughout my research career over 15 years. These moments are very rare. You do an experiment, and the result is very clear. It is telling you something very clear that makes you just go WOW."

Can you describe the feeling in that moment?

"Instead of “Eureka!”, I typically shout out “Nature paper!” in reference to the prestigious scientific journal. The idea of having a discovery in your hands triggers the desire of becoming a famous scientist. But not only: it feels like when you see a twist at the end of a movie that you did not see coming and then you want to tell everyone about it."

 

Right now, I might be the only one knowing this in the entire universe

 

In science, it instead becomes a reverse spoiler alert, where you can tell everyone about your discovery. Contrary to the movie analogy. But how can you know you are the first person doing this discovery?

"You cannot always be sure, that's why scientist always say, “to the best of my knowledge no one knows this”. You cannot be sure no one else ever discovered that. You can look in the literature, but if it is a problem you have worked on for a period of time, you have already checked in the literature. So, when you have this type of result you have this feeling of "in the known universe I am the single organism knowing that" and that is cool."

 

Sharks, dinosaurs and prose

Claudio Cantù holds a design of Tyrannosaurus Rex made from LEGO that sits on his bookshelf in his office.Claudio Cantù holds a design of Tyrannosaurus Rex made from LEGO that sits on his bookshelf in his office. Photo credit John KarlssonEarly on Claudio developed a desire to become a scientist. Maybe it was the interest in the natural world that paved the path. The countless illustration magazines with sharks and dinosaurs, that he to this day still buys, opened the door to the world of science.

"Since I was a child, I couldn't decide whether I should become a marine biologist or a paleontologist. The reason why is very simple as for many children. I liked sharks and dinosaurs. This is something I still have with me to this day."

In high school Claudio had it relatively easy for subjects such as chemistry, biology, and math, but he didn't really enjoy it that much. People around him told him to become a medical doctor, but he preferred to focus on topics he liked.

"I was 19 at that time and I didn't care about finding a job, I just wanted to look at what I like. I sort of never lost that."

The urge to understand the world and all its complexities also fed his desire for literature around his early twenties. 

"I like prose. I appreciate texts where things are explained in a clear manner so that anyone could understand them. I also like grammar and the analysis of the structure of a text. This is something that I bring with me to this day in my job at LiU. As scientists we need to communicate our discoveries by writing articles, or convincing funding agencies by writing scientific proposals. The writing is a big part of my job, and I enjoy it a lot."

Magical first year

To keep the option of becoming a marine biologist alive, Claudio decided to study Biological Sciences at the University of Milano-Bicocca. Then something happened.

 

I think I fell in love with the discipline of genetics

 

"In year one of university something happened. I started studying genetics. It might sound weird but, I think I fell in love with the discipline of genetics when I was studying the work of 21-year-old student Alfred Sturtevant."

Alfred Sturtevant was a student of a very famous scientist called Thomas Hunt Morgan in the early 1900s. Sturtevant's most notable discoveries include the principle of genetic mapping. The story Claudio is referring to is when Alfred spent a night thinking about a problem they had in their lab. In that night he was the first person drawing a physical map of a chromosome. That was around 110 years ago.

"By combining experimental observations and intellect this young student could describe something sophisticated yet so small that cannot even be observed directly, and he was right! My astonishment derives from the fact that what he discovered corresponds to events that happens on the scale size of the DNA. These molecules are smaller than wavelength of light. They cannot be seen, even in principle."Male researcher in university surrounding.Claudio Cantù. Photo credit Ulrik Svedin

That first year in university convinced Claudio that the peak of his desire was to become a molecular biologist. Animals are interesting, but the smaller parts of which they are made, are even more so.

"The very fact that we can understand things that are incredibly complex yet elude our primary senses and sometimes our intuition. I wanted to do something along those lines. This somewhat overcame the passion for both sharks and dinosaurs. I now sometimes regret this choice", smiles Claudio.

 

In five years

In 2027 Claudio will be 45 years old. What has happened then?

"I hope that we will have achieved two things. One, is opening at least one of the many unopened doors that will reveal how the genome works. Making a real contribution in science might mean that your discovery is real, and might not be disproved until the end of the universe."

And the other?
"The other is successfully completing this half-discovery that we have right now, where we observe a key difference between colorectal cancer cells and normal colon. That relies on our understanding of development. I hope that these two things might have been achievable in five years."

Any other goals?
"I have a writing project of popularized science, in which I desire to describe to everyone what I do, describing this marvelous discipline that is developmental biology."

Facts about Claudio Show/Hide content

Most important book?
"There are two very important books in my life. One is The Long Walk from Stephen King. It was the book that taught me the pleasure of reading. I was eleven and it was the first time when I could not stop going through the pages. The second book, perhaps the first in order of importance, is The Selfish Gene by Richard Dawkins. I call Dawkins an intellectual hero. When I read his writings, I am almost moved by his clarity, and I feel glad that there are persons in the world with the sharp intellect to understand and explain genuinely sophisticates phenomena. His books are a paragon of prose to which I aspire when I write."

Best about being a researcher?
"That this job almost never repeats itself. As a researcher, you are always looking for a new question, a new discovery, using new technology. It's never boring. I always have the feeling that you are always learning something. And I almost invariably think of myself of the previous year as stupid. I take this as evidence that I must have learned something in the meantime." 
Any hobbies?
"Reading and running, even if these are more obsessions than hobbies. And, even though I just turned 40, I still buy LEGO sometimes."
Male researcher in university surrounding.Claudio Cantù. Photo credit Ulrik Svedin This portrait is part of the reportage series Young Promising Researchers at the Department of Biomedical and Clinical Sciences (BKV) at Linköping University.

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