From Soldering Iron to Molecular Switch

Thanks to funding from the new Cluster of Excellence CIBSS, Centre for Integrative Biological Signalling Studies, scientists now have the opportunity to build further on Freiburg’s already well-established signaling research, thus also opening up new perspectives for students. “The University of Freiburg was able to appoint highly qualified colleagues, thanks to whom we can now introduce new teaching modules offered exclusively in Freiburg,” explains Wilfried Weber, professor of synthetic biology at the Cluster of Excellence BIOSS, Centre for Biological Signalling Studies, and a member of the team of spokespersons for CIBSS.

Whereas BIOSS focuses on biological signaling processes at the various levels of an organism, investigating how they are organized at the molecular or cellular level or in the entire organ, the aim of the new cluster CIBSS is to build on the knowledge gleaned from this research. The participating researchers are setting their sights on the interplay between the individual signaling pathways. “We’re no longer just looking at what happens at the various levels but trying to understand how the signals are transmitted along these levels,” says Weber. The guiding questions of CIBSS are: How can a signal occurring at the molecular level within microseconds in the nanometer range have a lifelong impact and influence large organisms? “How do the 30 trillion cells in our body,” asks the biologist, “manage to orchestrate things so that each cell does not simply do whatever it wants but cooperates with all of the other cells to make up a healthy organism?“

Switching Signaling Pathways On and Off

How can researchers study a complex process of this kind, which might begin with a molecule binding to the receptor of a cell wall, setting off a cascade of signals to the cell nucleus, where particular genes are then switched on and off? What effects do communication processes within a cell have on a network among the tissues of many cells? What happens in what cell, on what day, and in what minute during the development of the ovum to an embryo? To investigate such processes, scientists in Freiburg attempt to switch specific signaling pathways in individual cells on and off. “We build a molecular switch,” says Weber. This is also the aspect of the research that involves a great scientific leap forward, because flipping a molecular switch in the cell involves producing a signal that the switch reacts to. The Freiburg scientists accomplish this through optogenetics, a technique through which genetically coded elements in the individual cells can be switched on and off by means of light.

“I can apply any amount of light for just the amount of time I need it – one day or two days, one hour or one millisecond – and I can use a laser to accurately illuminate single cells. This makes it possible to control biological communication processes with previously unheard of spatial and temporal precision,” says Weber of the advantages offered by this technique. But applying it initially involved solving several practical problems. “Biologists generally know very well how to generate molecular switches that react to optical signals,” says Weber, “but how does the light reach the precise point where it needs to go? We didn’t have any illumination devices for this at first. We had to design and build them ourselves. But biologists have no training in this area.”

The world of optogenetics: Researchers can use light to switch on and off genetically coded elements in the individual cells. Photo: Thomas Kunz

Engineering Meets Biology

As the approach of optogenetics already played a key role in BIOSS and does now again in CIBSS, the participating scientists decided to develop a joint teaching module with the Faculty of Engineering. “Students of biology and microsystems engineering learn to combine their educational backgrounds to do things that would not be possible for one discipline to do on its own,” says Weber to explain the basic idea for the “Engineering Meets Biology” profile module. The students of both faculties practice controlling biological processes with optical signals by designing molecular switches that can be turned on and off with light. While the biology students contribute their know-how concerning DNA and cells, the future engineers help them out when it comes to constructing illumination devices, working with a soldering iron, and installing microcontrollers.

Cooperation beyond Disciplinary Boundaries

The construction of molecular switches is a particularly good example of how much BIOSS and CIBSS also profit from the tightly integrated work of the various sub-disciplines of biology. A muscle cell, for instance, does not react to light signals on its own. It first needs to be taught to do so. “Here we benefit from the strength of Freiburg plant research. Our colleagues have done a lot of research to determine which photoreceptor molecules plants use to discern light of different wavelengths. Thanks to their work, we can now transfer receptors from plants to muscle cells and optogenetically control them,” explains Weber. However, it’s not enough to just get communication processes going through optogenetics. The researchers also need to be able to observe them. To do so, they practice using the most modern microscopy methods. Analyzing the enormous amounts of data thus produced by hand would not be very effective. They thus ask computer scientists to write analytical programs designed to identify what a cell is, measure how strongly the cell is illuminated, and produce good analytical sequences.

A Common Language and New Skills

The interfaculty learning can be quite a challenge. The computer scientists do not necessarily possess detailed knowledge about the structure of a cell or DNA, whereas the biologists are at a disadvantage when it comes to differential equations or soldering. “It takes time to find a common language,” says the teacher. “That’s why we took care in designing the joint teaching module to have the students of the two faculties get together early on in their course of study and fill each other with enthusiasm for their discipline.” The biologists certainly realize how much they profit from the engineering aspect, says the professor. And the engineers are keen to develop new algorithms and imaging methods because they’re well aware that these skills are currently in great demand in medicine, for applications like the automatic analysis of x-rays. “We offer just what the students need to learn these skills on the basis of useful research,” Weber explains. “But the biology students too have requested to have more such interdisciplinary elements included in their studies. So there’s interest on both sides.”

This is a request the professor and his colleagues from the Faculty of Engineering aim to fulfill in the coming semester, among other things by adding a new module. They have previously offered 25 to 30 slots per semester, roughly two-thirds of which are filled by biology students and the other one-third by engineering students: “But there are always more registrations than we can accept, and we’re overbooked every year,” says Weber. It’s not always easy for the teachers due to the different examination regulations, module structures, and ECTS credits. “It takes the motivation of everyone involved to find pragmatic solutions”, says Weber, “but we’ve managed this already for our module.”

Jürgen Reuß