Utrecht has built an international reputation when it comes to cell biology. For this reason, the ERC starting grant Bert Janssen received falls in fertile ground at the Kruyt Building. Janssen investigates the communication between neurons. His focus is on notch and contactins, two protein molecules on the cell surface.
In order to truly understand how they work, Janssen investigates the proteins both separately and as part of many molecules on the cell surface. Using not yet fully developed technologies, he makes the so far invisible interaction between cells visible.
Text: Youetta Visser
"We know much about the biophysics and continue to discover more about the development and function of cells," Janssen notes. "But strangely enough, we still know little about intercellular communication. This is a missing link in many research projects. We already know much about the proteins I investigate in the ERC project, notch and contactins, so we have a solid basis. The question is how they communicate from the outside with the inner cell (in cis) and how they communicate with other cells (in trans)."
"Until now, we have investigated the functions of these molecules in isolation by means of protein crystallography. My research team and I will take on the challenge to test the hypotheses that are based on this method in the bigger picture." In reality, the proteins function among thousands of other molecules on the exterior of the cell surface. They form patterns, sometimes coagulate, make contact with each other or not and pass on all kinds of signals, in cis and in trans at the same time. Janssen says: "I think the way in which the molecules on the cell surface are organised has a big influence on the communication. Up until now, this detailed organisation has never been proven."
Janssen is a structural biologist by trade. "I did PhD research on the protein structures of our immune system. I became interested in cellular essays and neurobiology at Oxford. After returning to Utrecht, I continued on this path." Janssen's goal is to fathom the system. However, he has ideas on how this knowledge could be applied. "If we know how the communication works, we might eventually be able to deal with the malfunctions in the system that can cause illnesses such as cancer and nervous system disorders. It turns out there is often a kind of filter active that prevents signal triggering until a set number of interactions has been reached. If we know more about this, we might be able to adjust it." The ambition to figure out the interaction between molecules has set high stakes. "The difficult part is that notch and contactins influence each other as well. In order to study that effect, we will have to study their separate functions first and then study them together."
Janssen uses different methods for his research, which he sometimes develops further as he goes. "In order to prevent the research from stagnating if a certain method functions insufficiently, I came up with several alternatives in advance. For an example, it is difficult to study the interaction between notch and contactins inbetween cell membranes. I try to make that possible by covalently connecting these proteins to liposomes. But if that doesn't work, I could also try to let self-cultivated cells secrete cell vesicles. Finally, we mix the molecules on Surface A with those on Surface B and literally see what happens."
Why can this research be done in Utrecht? "Because we have acquired the expertise and can combine it with the materials we need. I have a large quantity of both purified and isolated proteins at my disposal. We cultivate the cells ourselves, separate the proteins, modulate them and store them in a solution afterwards. On top of that, Utrecht University has been investing in high-tech microscopes for a few years. "I will visualize the interaction by using the new electron microscope in the basement of the de Wied Building."
Utrecht has another advantage. "We cooperate really well here. I collaborate with Casper Hoogenraad, Lukas Kapitein en Albert Heck whoare experts on fluorescence microscopy and mass spectrometry. And also with Jeroen Pasterkamp from the University Medical Center Utrecht. I've got the world's experts close at hand."
It is clear now; this driven researcher is at the right place at the right time. After the interview, I pass by the offices of five other ERC laureates while walking through the corridor on the 8th floor of the Kruyt Building.