Professor Urs Jenal is a member of the European Academy of Microbiology (EAM). The EAM is a leadership group of around 130 eminent microbiology experts who came together in 2009 to amplify the impact of microbiology and microbiologists in Europe.
Professor Urs Jenal is based at Biozentrum at the University of Basel, Switzerland and specializes in infection biology. This week we caught up with him to find out more about his research interests.
What are you currently researching?
“We are currently busy defining the components of the c-di-GMP signalling network in several bacterial model organisms and working to understand how they determine the cellular program by influencing the c-di-GMP pool. To reach this goal, we collaborate with structural biologists and biophysicists to determine the molecular principles of such components and with computational biologists who help us to better understand the overall design principles of this regulatory network. This work is supported by the Swiss National Science Foundation and by the European Research Council.”
What has been the most unusual or surprising finding in this line of research?
“We recently found that the two largest signalling networks of bacterial cells – two-component phosphorylation cascades and c-di-GMP – closely cooperate to drive cell growth and propagation. We can now show that in Caulobacter crescentus, c-di-GMP directly binds to a central cell cycle kinase, thereby switching it from its default kinase state into a phosphatase. This switch regulates entry into the cell division cycle and is orchestrated by oscillations of c-di-GMP levels during the cell cycle. In essence, this finding suggests that bacteria, akin to eukaryotes, exploit the oscillation of cyclin-like molecules to drive their cell cycle.”
What has been the most challenging aspect of this project?
“The biggest challenge of this project connecting biochemical findings to cell biology and cellular function. Many of the newly identified components of the c-di-GMP network were isolated biochemically. While genetic studies always provide the experimentalist with a phenotype and thus with a clue about the function of a specific gene or protein, this is not always the case when novel cellular components are defined biochemically. Oftentimes, KO mutations of the respective genes may not provide obvious phenotypes and thus no indication of their function. Defining functionality within a complex and often redundant regulatory network can be challenging.”
What aspect of this project have you most enjoyed?
“I enjoy most aspects of fundamental research. I particularly like to discuss novel findings and their potential implications with my students and postdocs.”
What are your future hopes for this research?
“Together with my many colleagues studying interesting microbes, I hope to make important contributions towards a better understanding of bacterial cells and how they integrate and process information to direct their growth, behaviour, and survival. Eventually, this will lay a solid foundation of knowledge that will enable mankind to better control bacterial pathogens and to better exploit beneficial bacteria for the common good. On a more modest level, I would be very happy to reach some quantitative understanding of the signalling networks operating in some of my favourite ‘bugs’.”
How do you see this work impacting the field of microbiology?
“C-di-GMP is clearly one of the global control hubs in many bacteria affecting a plethora of cellular processes and behaviours. Since c-di-GMP is not used by eukaryotes, it represents an attractive target for interference with bacterial growth or with specific bacterial behaviour. For instance, c-di-GMP appears to control virulence and persistence in important human pathogens. It is thus plausible to postulate that detailed knowledge of such information transfer systems at some point in the future will help us to design novel antimicrobial strategies.”
How many people are in your research group?
“Currently we are 15-18 people, depending on how many Master students populate the lab.”
How would you describe the balance of group and individual work in your team?
“Because we work together very closely with structural biologists, we are naturally organized in small project-oriented teams combining different expertise. The concept of small project-related groups is also successfully applied within my own group where often a postdoc works together with a PhD student and/or a Master student.”
How do you collaborate with group members?
“I talk to the members of my group regularly in scheduled face-to-face meetings. I also like to drop into the labs on a more irregular basis to discuss projects, progress, or recent relevant publications. Intense scientific discussions over a cup of coffee can be very productive and generally generates lots of creative new ideas.”
Do you socialize with your research group members beyond the lab? What do you do together?
“I did socialize a lot with my lab when the group was smaller. Now that we have grown in size, this is limited to a few social gatherings throughout the year.”
Where do you find inspiration for your work?
“I found out that physical exercise stimulates my mind. New ideas, insight or intuition often come when I ride my bike or when running through the woods.”
What has been your most memorable moment in a lab (or in the field) thus far in your career?
“I do cherish the moments when things fall into place and when it dawns on me that things that just hadn’t been making sense become obvious and accessible. Of course, these moments don’t happen every day, but when they do, they are simply great and memorable moments.”
Would you describe a memorable ‘breakthrough moment’ or an instance wherein you overcame a particularly challenging obstacle in your work?
“Years ago, we were searching for an effective and rapid method to enrich and isolate novel c-di-GMP binding proteins directly from cell extracts. Together with a company in Germany, we developed a trivalent chemical scaffold with an affinity group, a cross-linking moiety, and a sorting function. The idea was to combine this tool directly with mass spectrometry to quickly identify candidate proteins. Because the company was not willing to share the development costs, the financial risk for this project was entirely on our shoulders. The technique turned out to work like a charm and has since helped us to isolate numerous proteins and initiate several new projects. I remember the very moment when my postdoc came into my office to show me the data with all the positive controls in the basket. At that time, this was a real breakthrough for us. This has taught me that there is no real progress without taking risks. I believe that apart from the willingness to work hard and the ability to manage failures, the most important quality in basic research is courage.”