The brain is the last great frontier - Joris de Wit

15 June 2013

​“When I was fourteen, I already knew I wanted to be a scientist. I was fascinated with biology and how things work. The brain is the last great frontier,” says Joris de Wit. After 12 years of brain research at the Netherlands Institute for Neuroscience (NIN) in Amsterdam, the Free Amsterdam University and the University of California in San Diego, USA, he has not lost any of his passion for neuroscience. This year, Joris started as group leader at the VIB Center for the Biology
of Disease, KU Leuven.

What is your research focus?
Neurons make connections. This does not happen randomly. They create very specific circuits, similar to computer chips. If the connections are defective the circuit does not function. In recent years, it has grown increasingly clear that numerous cognitive disturbances, including autism, schizophrenia, ADHD and Alzheimer’s, are associated with defects in the creation or function of synapses – the connections between the neurons. To understand these very complex diseases, we first have to understand at the molecular level how neurons form synapses, what ensures that they are functional, and what happens when the process is disrupted. That is the focus of our research.
 
The enthusiasm here is comparable to what I saw in San Diego. I recognize that ‘can do’ mentality here that is so characteristic of Americans. And that is invigorating.

 
 
 
 
We use cultured neurons. This gives us a greatly reduced system that can be easily manipulated but which is also far removed from a truly functional brain in which innumerable neurons are interconnected.  Cultured models will always remain a component of the research because they provide a versatility that is much harder to achieve in vivo. Cultured systems can contain several different types of brain cells – neurons, of course, but also, for example, glial cells. Such complex cultured systems allow us to visualize individual cells and the contacts they form. But, of course, the best thing in the long run is to look inside the brain, and even inside living, functional organisms such as rats and mice.
 
Are there any collaborations with NERF?
Not yet. What is going on there is super relevant for my work but not the main reason why I came to Louvain. It’s terrific, though, to have NERF nearby. They really are conducting analyses at the systems level. By working with them, we can cover the entire spectrum, i.e. gain a molecular and mechanical understanding of the formation of the synapse as well as look in vivo at how synaptic deficits affect the behavior of mice. That would be great.

After six years of research at the University of California San Diego (UCSD), you returned to Europe. Why? And why Flanders and not Amsterdam?
Definitely not because of the weather! My main reason was personal. We have children and wanted to be closer to our families. I also will personally never feel American. The choice of Flanders was influenced by multiple factors. The first one is the scientific environment in this department – the quality of the other group leaders, the independence you are given, and the numerous facilities that are available in, for instance, the field of microscopy. The enthusiasm here is comparable to what I saw in San Diego. I recognize that ‘can do’ mentality here that is so characteristic of Americans.  And that is invigorating. The department is also very international. Almost all of the group leaders were recruited abroad. And it truly is a PI-based organization. Researchers with their own lab and their own budget work within a larger department with a director who encourages independence. That is what I experienced in the US for six years, and that way of working really suits me.

To make money we have to acquire new knowledge on the frontiers of science. And VIB has proven that investments in basic research, innovation and knowledge pay off economically.

 
 
 
 
 
I could have gone to three places: Amsterdam and two places in Belgium. The fact that I received an ERC grant also helped me make up my mind to come here. It gave me mobility. The fact that this department has a number of other ERC recipients (Jan Cools, Bart De Strooper, Matthew Holt, Anna Sablina, Patrik Verstreken) gave me a sense of credibility. It assured me that I was able to work at a certain level. ERC is an excellent mechanism for recruiting people. It is a fantastic tool is you succeed in getting it. At the same time it is extremely competitive and people that are very good may still not get it. 
 
Also for Floor (his wife, Floor Stam, works as Business Development Manager at VIB) Flanders was the best option. After a PhD and six years of postdoc work in neuroscience, she wanted to make a switch to technology transfer. And Belgium is further ahead than the Netherlands in that area. That VIB was constructed around this idea was an eye opener for me. In the Netherlands, science is often considered an expensive hobby. Here it is viewed completely differently: to make money we have to acquire new knowledge on the frontiers of science. And VIB has proven that investments in basic research, innovation and knowledge pay off economically.

What are your thoughts about Obama’s BRAIN project?
I think it’s great. The fact that he supports it sends a signal that brain research is important. The project right now seems mostly like science fiction but top scientists have lined up behind it. Just like the work they do at NERF – looking at neurons in the brains of living animals, activating and inactivating certain neurons, etc. – was still considered science fiction ten years ago. It is just like going to the moon – we set an ambitious goal and in the end it is primarily the technological innovation generated by this kind of project that will create an avalanche of new applications years later.
 
What are the challenges in brain research?
The greatest challenge is truly understanding how the brain works – how memory works, where memories are stored, emotions, all those complex issues. I don’t know whether I will live long enough to see it. Given the enormous progress that has been made in recent years, though, there is reason for hope. Neuroscience used to be a field that lagged way behind, but no more. First, we have to understand how neurons connect with each other in the brain so that we can map the connections – not only the connections themselves, but also the activity that passes between the cells, the information stream. Those are also questions the European Brain Project is planning to address. But that is only the beginning. It is the age-old proven scientific approach. First look what you can find and then how it works. The scale of the work – 100 billion neurons with each 10,000 connections – is almost impossible to imagine. It can certainly be done for individual brain regions and it will be quicker for simple organisms.

Research

From left to right:
Joris de Wit, Giuseppe Condomitti, Kristel Vennekens & Emilia Iscru