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Wilfried Weber recombines new cell constituents

For a long time, biology was a purely analytical science. Now with the latest knowledge of the functions of individual cell components, a new field is developing known as synthetic biology. Prof. Dr. Wilfried Weber, who was appointed professor of synthetic biology at the Centre for Biological Signalling Studies (bioss) at the University of Freiburg in May 2009, has always had a great interest in the practical application of biology. Weber and his team have a thorough understanding of how different parts of signalling networks can be reassembled for specific purposes, for example, switching off the antibiotic resistance of bacteria.

Prof. Dr. Wilfried Weber © Prof. Dr. Wilfried Weber

"In terms of chemistry, something similar happened in the Middle Ages," said Prof. Dr. Wilfried Weber. "However, in the Middle Ages, the alchemists would just mix substances and wait and see what happened." In the centuries that followed, chemists gradually obtained greater insights into chemical principles and were hence able to combine the individual components as required. Modern synthetic chemistry has entered almost all areas of life. What is true for chemistry can also be true for biology. Many molecular mechanisms of cells are known. Modern biologists have a comprehensive knowledge of the systemic relationships of entire signalling and gene networks. "Wouldn't it be a good idea to recombine known biological constituents and use them for new applications?" asks Weber.

Playing with biological construction kits

Weber, born in Reutlingen in 1974, became interested in this more constructive side of biology at the beginning of his professional career. After he finished school, Weber decided to study biochemistry. After his basic degree, he moved on to Strasbourg to register for the trinational biotechnology course. “Strasbourg University offered biology and biochemistry, but in addition to these two disciplines, it also offered courses in process engineering and engineering science,” said Weber highlighting that this combination suited him perfectly. He did his doctorate at Novartis in Basel, where he became acquainted with the application of biological systems for industrial purposes. Weber optimised the production of proteins in insect cells by more than 80 per cent, for which Novartis gave him a special award in 2000. In addition, he was also awarded the Biotechnika Student Prize for the best degree thesis published in 2001.

Weber did his postdoctoral at the ETH Zurich between 2000 and 2003. His biological work focused on the discovery of new biological systems which could be used to produce antibodies, hormones and other proteins artificially, though at the same time Weber received training in company management. Together with his supervisor, Prof. Dr. Martin Fussenegger, Weber established Cistronics AG, a company set up to develop new antibiotics and sell protein manufacturing processes to industry. The profits made with these services were used to cover their further research. Weber then moved on to the Institute of Biotechnology (2003 – 2005) before becoming the head of a research group at the ETH Institute for Chemical and Bioengineering until 2008. Weber’s research showed a growing potential for application. Weber and his team discovered that it is possible to switch off the antibiotic resistance of the tuberculosis pathogen. This is an excellent example of how synthetic biology can be put to good use.

The tuberculosis pathogen Mycobacterium tuberculosis under the electron microscope. © Centers for Disease Control and Prevention: Dr. Ray Butler and Janice Carr

"Many bacteria are developing resistance to antibiotics, which poses a growing problem, especially with regard to treating infectious diseases," said Weber. "The pharmaceutical industry is working hard to develop new antibiotics, but this is not easy. We are trying to do it the other way round." Antibiotic resistance develops as a result of environmental pressure; bacteria that are able to survive the exposure to antibiotics will live on and pass this trait to their offspring, which will become fully resistant. This process is mediated by complicated bacterial signalling networks. Weber and his team have analysed these signalling networks in tuberculosis bacteria by isolating them and integrating them into human cells. The combination of different bacterial components finally led them to discover a weak spot that could be targeted with the molecule BV6481, and resulted in the loss of the bacteria's antibiotic resistance. BioVersys GmbH, a company co-founded by Weber in 2008, is now pursuing further research in this area and Weber serves as the company's consultant. Further bacteria will be investigated; for example multiresistant bacteria in hospitals which pose a risk to many patients that have undergone surgery.

At the centre of different disciplines

“The new position at Freiburg University offers new challenges,” said Weber. The 35-year-old is currently working on the establishment of his research group at the bioss. He is pleased to be working in an interdisciplinary team together with physicists, engineers, biologists, chemists and computer scientists. According to Weber, progress in synthetic biology can only be achieved when researchers from these disciplines work closely together. One of his current projects focuses on the development of intelligent drug depots with embedded therapeutic substances that can be released in a dose-dependent way by way of a switcher. Synthetic biology will also play an important role in this process. The drug depots, which consist of specific polymers, will contain constituents of natural signalling systems, which will be released following a certain command. All this is still a plan for the future, but the researchers hope that it will not be long before an orally administered small molecule (an activator) will be available to release the therapeutic substances embedded in the drug depot.

Prof. Dr. Wilfried Weber and one of his colleagues in the laboratory. © Prof. Dr. Wilfried Weber

A lot of research will be necessary before this dream can become reality. Weber and his team want to gain insights into how the underlying signalling networks function, identify the components and conditions that are necessary to create such drug depots. Does this leave time for a family? The scientist, who previously used to sail and row a lot, nowadays enjoys every free minute with his three children aged one, three and six. The family still lives in Switzerland where Weber's wife works in Basel. However, the family has plans to move to Freiburg in September. "Freiburg is ideal for families," said the very content biotechnologist.

Further information:
Prof. Dr. Wilfried Weber
Centre for Biological Signalling Studies (bioss)
Institute of Biology II
Schänzlestr. 1
University of Freiburg
79108 Freiburg
Phone: +49 (0)761/203-97654
E-mail: wilfried.weber(at)bioss.uni-freiburg.de

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/wilfried-weber-recombines-new-cell-constituents