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Christiane Wobus does norovirus research in two completely different environments

Prof. Dr. Christiane Wobus researches mouse-specific noroviruses. The virologist is seeking to clarify the interaction between viral particles upon contact with host cells. The scientist normally lives in the USA, but has returned to Germany for a 12-month period thanks to a Humboldt Fellowship. She will be working at the Interfaculty Institute of Biochemistry at Tübingen in Germany where, amongst other things, she highly rates the cooperation opportunities available. Having been in a position to compare the pros and cons of research in Germany and the USA, she is quite positive about returning to Germany at some stage in the future.

Prof. Dr. Christiane Wobus is one of around 25 outstanding international woman researchers to have been awarded the Humboldt Foundation’s Friedrich Wilhelm Bessel Research Prize that involves a research stay in Germany. © Amanda Crain

Dr. Christiane Wobus owes her research stay in Tübingen to a typical American tradition. "In the USA, professors with a permanent position can take a sabbatical every seven years," says Wobus. While many of her colleagues spend their sabbatical at an American university, Wobus and her family decided to do things differently. "The opportunity to rediscover Germany appealed to us, and we also liked the idea that a sabbatical would give us a new perspective on our work." Back in the 1990s, Wobus, who is originally from Saxony-Anhalt, and her husband, an American national and also a biologist, had already spent some time in Baden-Württemberg. After her master's degree studies at Michigan State University, she came to Heidelberg to do her PhD on the use of adeno-associated viruses as gene vectors for therapeutic applications, while her future husband was carrying out research at EMBL.

Around the turn of the millennium, the two returned to the US, where Wobus initially worked as a post-doc at Washington University in St. Louis, and from 2007 onwards, as assistant professor at the University of Michigan in Ann Arbor. In 2014, she qualified for a tenure professorship and so was able to obtain a permanent position. The tenure system is different from the system in Germany, where young scientists are still often required to have a habilitation before applying for permanent professor positions. "In the US, you apply for a tenure professorship by submitting information on a range of qualifications, including the number of papers you have published, third-party grants you have acquired and your international reputation. There is no examination as in the case of the German habilitation," says Wobus.

When she got the tenure, the pair already had two children and had set up home in the area around the Great Lakes (Michigan, Huron and Erie). The virologist is full of praise for the fact that in the USA it is a lot easier to combine work and family, especially when she found out how difficult it can be in Germany. "In the USA, seminars and meetings are usually scheduled between 9 a.m. and 5 p.m., which is when the children are usually in child-care institutions. A kindergarten that is closed in the afternoon is inconceivable in the US." However, child-care is less costly in Germany than in the US. "The fees we pay here for nurseries and kindergartens are much higher than in Germany," says Wobus.

It is easier – though more expensive – to combine job and family in the USA

Host cell entry of the murine norovirus occurs in several steps. At first, the virus binds to sugar residues on the cell surface (attachment receptor). Whether and how, in connection with this event, a surface protein acts as internalisation receptor is still being researched. © Wobus, University of Michigan

When Wobus applied for a Humboldt Fellowship, the whole family was involved in the decision. So it was not just scientific reasons that led to the decision to spend a year in Tübingen. Tübingen University also invited her husband to spend some time as a visiting professor at the ZMBP (Centre for Plant Molecular Biology). Another important part of the family's decision to go to Tübingen was the presence of Prof. Dr. Thilo Stehle as director of Tübingen University's Interfaculty Institute of Biochemistry (IFIB) and whose work specifically involved viruses, including noroviruses. These RNA viruses are the most common cause of viral gastroenteritis in humans, and frequently lead to epidemic outbreaks. Wobus has been working with noroviruses since her post-doc period. "I have long been fascinated by the tiny virus's ability to modify the cells of the host it infects despite having a very small genome, even by viral standards."

Wobus now works with mouse-specific noroviruses and is hoping to be able to clarify the interaction between virus particles as they establish contact with host cells. "It is known that the viruses dock to the sugar components on the cell surface of immune cells. The sugars act as a kind of glue for the viruses. However, other reasons for the importance of the sugars are still largely unknown. We are also interested in how the virus interacts with peptides on the cell surface, thus initiating its internalisation or triggering signalling pathways in the host cell," says Wobus.

It is interesting to note that noroviruses not only bind to the sugars on the surface of their host cells, but also to sugars on the surface of bacteria that are abundant in the human gut. It seems that the interaction with the bacteria plays a crucial role in bowel infection. Wobus explains why: "We have observed that the infection rate of bacteria-free mouse intestines is significantly reduced. It is still a mystery how the virus can infect the host so efficiently, as binding to the bacteria would normally prevent them from doing this. Purely mechanistically, the virus would have to release the bacterial cell in order to be able to enter the host cell."

Although these issues still need to be dealt with in depth at the molecular level, knowledge of the interactions will be of great benefit for medical application. "In developing countries, patients are generally badly affected and disease progression is usually rather dramatic. Around 800 children a year die from norovirus infections in the USA, while the disease kills around 200,000 children in developmental countries," says Wobus.

German culture of cooperation scores high

Cryo-electron microscope image of a mouse-specific norovirus. Different colours mark the different domains of the virus. © Thomas Smith, Donald Danforth Plant Science Center, St. Louis

Christiane Wobus has been working on these issues with colleagues from the IFIB since August 2014 and particularly appreciates the culture of interdisciplinary cooperation in Germany. "Germany focuses mainly on large-scale projects which exploit the potential of previous collaborations. In America, we work more according to the cowboy principle, which means that a single person does everything. In order to be eligible for tenure, you have to prove your independence from your previous mentor. Joint publications with the mentor do not count when you apply for a tenure position. This is why you wouldn't even consider applying for third-party funding with your former boss." Wobus also finds that collaborative research provides researchers with relatively easy access to experts and expertise across different locations.

All in all, Wobus can now well imagine returning to Germany and is sure that her husband and her children would not be against the idea either. One good reason for this is that it is no longer as easy as it was to acquire funding for life sciences projects in the USA. "However, both of us would have to be offered a job in the same city. This is a prerequisite for us to return to Germany. Returnee programmes work quite well for one person, but not so well for couples, at least in my opinion," says Wobus. That said, they have already put their feelers out to see whether a return to Germany is possible.

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