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The masters of cellular circuits

Can life be copied? The innovative field of synthetic biology has been trying for many years to assemble cellular components into new systems with pharmaceutically desired properties. The research group led by Prof. Dr. Wilfried Weber from the Centre for Biological Signalling Studies (BIOSS) in Freiburg was established just 18 months ago at the first German Department of Synthetic Biology. And another premiere: Professor Weber is the first scientist at the University of Freiburg to receive the prestigious European Research Council Starting Grant of 1.5 million euros to help him expand his research in the field of intelligent materials. One of Weber’s doctoral students has also recently received a prize. Weber’s team recombines cellular components and works on a broad range of different issues. The “cell engineers” make use of the interdisciplinary environment of the University of Freiburg. What can nowadays be constructed with molecular building sets?

Prof. Dr. Wilfried Weber's (third from the right) team from the Department of Synthetic Biology at the University of Freiburg. © Prof. Dr. Wilfried Weber

Each cell has switches on its surface that trigger molecular interactions inside the cell, including interactions on the DNA level. Scientists refer to these as signalling systems. The majority of diseases are the result of disordered signalling systems. How can these switches be manipulated in order to enable a cell to get back on the right track? Is it possible for researchers to isolate different circuits, recombine the elements and introduce them into other cells in order to induce desired reactions at the push of a molecular button?

The group of researchers led by Prof. Dr. Wilfried Weber, who was appointed head of the first German Department of Synthetic Biology at the University of Freiburg in May 2009, is focusing on the aforementioned questions. The group's goal is to investigate the interactions between cellular proteins and between proteins and DNA. These interactions can be controlled from the outside. Weber's group of researchers do not see themselves as just analytical biologists. "Our goal is to understand the interaction of biological components and recombine them in new ways," said Weber. Weber and his colleagues are all engineers who work in the field of biology.

Intelligent materials

Why does one want to copy parts of a cell? A good example is a project dealing with materials research. In cooperation with materials researchers, chemists and engineers at the University of Freiburg, Weber’s team succeeded in developing materials that can release therapeutic substances on command. The researchers combined artificial polymers with biological signalling systems and attached receptors which they had previously isolated from cells to the surface of microscopic containers. These receptors can bind signalling molecules that are added from the outside. The receptors transmit information about the presence of the signalling molecules into the cell where other molecules release the content of the containers to the outside. “Such intelligent containers might be used in the field of medicine,” said Weber. Currently, there are mainly materials that can alter their properties following temperature or pH changes. However, pH and temperature cannot be changed at random in the human body.

Weber and his team have implanted the containers into experimental mice and found that the administration of a certain signalling substance by way of drinking water or injection led to the release of a drug into the animals’ blood.

Intelligent materials that are used as therapeutic drug depots (droplets). © Christian Geraths

Weber has received the prestigious European Research Council (ERC) Starting Grant with a purse of 1.5 million euros, which will enable him and his team to continue their work on intelligent materials. "The grant is a major recognition of our achievements and motivates us to continue focusing on the concept of synthetic biology in the field of materials sciences," said Weber. The combination of materials research and synthetic biology is also of great interest for the Swedish doctoral student Maria Karlsson in Weber's team. Karlsson was recently awarded the Barbara Hobom Prize by the Freiburg-based Excellence Cluster for Biological Signalling Studies (BIOSS). The prize, which comes with a purse of 10,000 euros, is awarded to young PhD students working on promising doctoral projects. Karlsson, who has already done research stays in Singapore, Spain, Sweden and Switzerland, has found an excellent research environment in Weber's synthetic biology research group. She is now investigating how cellular signalling systems can be combined with new materials with the goal of finding a way to accurately control the growth and differentiation of cells.

An optimal infrastructure for innovations

Besides the aforementioned project, the scientists are also working on other approaches. They have recently created an interface between an electronic circuit and a cell. A circuit is able to release a signalling substance that can directly switch on genes in the cell. The scientists have developed an artificial gene switch that can be electronically controlled and in theory is able to trigger all possible cellular responses. It is still not known which applications the interface can be used for, but the researchers’ main concern was to provide proof of principle that it worked. In any case, the researchers succeeded for the first time ever in combining electronic circuits with modified biological material.

The work done by Weber’s team has already led to numerous applications in the field of therapy. Some years ago, Weber (then at the ETH Zurich) and the company BioVersys GmbH, of which Weber is a co-founder, succeeded in combining biological components in a way that inactivated the bacterial resistance factors in pathogens. One approach restored the sensitivity of the multi-resistant Mycobacterium tuberculosis to the antibiotic ethionamide. BioVersys GmbH is focusing on the further optimisation of the compound. In addition, Weber’s team has developed biosensors that are able to detect banned antibiotics in food, including milk. Weber’s 20-member team can certainly be expected to come up with further surprises. “The interdisciplinary environment at the University of Freiburg where we work with physicists, systems biologists, chemists, engineers, computer scientists and microsystems engineers as part of BIOSS certainly provides an optimal infrastructure for innovative developments,” concluded Weber.

Further information:
Prof. Dr. Wilfried Weber
Institute of Biology II
BIOSS - Centre for Biological Signalling Studies 
University of Freiburg
Engesserstraße 4b
79108 Freiburg
Tel.: +49 761/203 97654
Fax: +49 761/203 97660
E-mail: wilfried.weber(at)biologie.uni-freiburg.de

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/the-masters-of-cellular-circuits