Painting Proteins with Dyes: Prof. Kai Johnsson
Prof. Kai Johnsson is the driving force behind ground-breaking methods that make the hidden life of cells visible, such as SNAP-tag. Now, he is directing his passion for tinkering towards solving new problems, including biosensors that patients can use at home to monitor drugs or metabolites. Prof. Kai Johnsson is the Director of the Chemical Biology Department at the Max Planck Institute for Medical Research in Heidelberg and received this year’s Hansen Family Award.
Prof. Johnsson, during your career, you have developed different chemical approaches to study protein function. What motivates your research - what motivates you?
What motivates me is that the multitude of biological processes that take place in living cells still remain invisible for us. This precludes a molecular understanding of biological processes, including processes which also play a role in a number of diseases. Therefore, we develop methods to make biological molecules visible - we want to bring light into the darkness of the cell.
One fundamental development was protein labelling in living cells, for example with SNAP-tag. What did these methods allow scientists to do?
SNAP-tag is a small protein that can be specifically labelled with bright fluorophores and as this process can be even carried out in living cells, it allows us to paint proteins in selected colors. You can then visualize the labelled protein with a fluorescent microscope, thereby following it directly in cells.
What makes SNAP-tag so versatile?
SNAP-tag is a small protein that can be genetically fused to any other protein. SNAP-tag reacts with fluorophores but also other molecular probes, and so the SNAP-tagged proteins open up a multitude of ways of studying biological processes. Labs use SNAP-tag to investigate questions in different research fields, ranging from cancer to neurobiology.
What do you see as the highlights of your research?
I’m always most enthusiastic about my current work. But with some distance I have to say that SNAP-tag is the highlight, because it was the first general method to covalently label proteins with probes. I think what makes our research special from a technical point of view is the combination of biochemical techniques with synthetic chemistry, and the synergy that results from that.
In your current research you are working on biosensors. What is the motivation for this work and how do "biosensors for the home" work?
With our biosensors we would like to quantify the concentration of key metabolites, either in living cells or in patient samples. Such a quantification is a prerequisite for a molecular understanding of biology, but is also needed in medical applications, for example in diagnostics. Our biosensors for diagnostic applications are based on luciferases, which are proteins that can emit light. Luciferases for example can be found in fireflies. We’ve found ways to attach a fluorophore to the luciferase such that the luciferase changes the color of the light it emits in the presence of the analyte we want to detect. The color change can be detected with a camera and is suitable for quantification.
Where could such a biosensor be used?
One application is for patients with phenylketonuria, who cannot break down the amino acid phenylalanine. High phenylalanine levels during development lead to intellectual disability. To monitor treatment, the phenylalanine level in the blood must be checked regularly, usually by having a blood sample analysed in a hospital. With a suitable biosensor, patients could instead measure their phenylalanine levels at home, which would make the management of the disease much easier.
What other methods would you like to develop?
Currently, we are interested in developing novel methods to visualize neuronal activation in the brain. Our approach is based on painting active neurons with fluorophores. We hope that these methods will contribute to our understanding of how the brain works.
You have already co-founded several companies in the course of your career. How important is the commercial implementation of your solutions to you?
A central part of our research is the development of methods and tools, and the impact of a method depends on how many people actually use it. A prerequisite for the wide distribution of a method is that it is commercially available. Commercialization is an important part of making our methods available to other scientists.
What advice would you give to researchers interested in this knowledge transfer?
I would advise to just try it out. It often looks more difficult than it is. If someone has a good idea and sticks with it, they often find ways to achieve their goal. And even if the original goal is not achieved, which I have also experienced myself, you learn so much in the process – it’s a great experience.
What does societal responsibility of science mean to you?
I think a prerequisite for the well-being of our society is that all of its members feel responsible for it – this responsibility applies even more so to scientists, as society puts us in a very privileged position where we can pursue our passion. I believe that we scientists therefore have the responsibility to reflect on how our work ultimately could benefit society, whether through the development of new technologies, the creation of new knowledge or through the training of young scientists. I see this as my responsibility as a scientist.
What significance do prizes like the Hansen Family Award have for you?
It's a fantastic honour to receive an award as prestigious as the Hansen Family Award. When I received this award, I inevitably thought of other scientists who I thought would deserve this prize more than myself. But nevertheless, my peers selected me; this is what made this prize so special for me.
Interview: Sophie Fessl