In an interdisciplinary yet integrated approach, we apply molecular signaling devices for the design of synthetic signaling network within and across mammalian cells, for in vitro analytical systems, for the design of signal-sensing and -transducing smart biomaterials and for the discovery of new drugs interrupting the signal cascade responsible for antibiotic resistance in tubercle bacteria.
Synthetic signaling networks within and across mammalian cells.
Based on modular biologic devices (so-called biobricks) we design synthetic gene network within mammalian cells showing complex dynamic behavior like adjustable time-delayed expression kinetics. By designing inter-cell communication systems (so-called cell-phones) we emulate the coexistence of different species in synthetic ecosystems or construct synthetic hormone systems enabling cell-to-cell signaling within mammals. Furthermore, the implementation of electro-genetic interfaces enabled the direct coupling of microelectronic circuits to synthetic gene networks as exemplified by electro-genetic frequency detectors or frequency generators.
- A synthetic mammalian electro-genetic transcription circuit. Nucleic Acids Res. (2009) 37:e33
- Synthetic ecosystems based on airborne inter- and intrakingdom communication. Proc Natl Acad Sci U S A. (2007) 104:10435-10440
- A synthetic time-delay circuit in mammalian cells and mice. Proc Natl Acad Sci U S A. (2007) 104:2643-2648
- Gas-inducible transgene expression in mammalian cells and mice. Nat Biotechnol. (2004) 22:1440-1444
- Macrolide-based transgene control in mammalian cells and mice. Nat Biotechnol. (2002) 20:901-907
In vitro analytical systems
Based on antibiotic-responsive DNA-binding proteins we designed simple and economic test systems for the detection and quantification of forbidden antibiotics in foodstuff like milk. The test systems are available either as multiparallel microtiter-based ELISA for analysis in laboratories or as semi-quantitative dip-sticks suitable for rapid on-site analysis.
- Dip-stick-based approach: A novel generic dipstick-based technology for rapid and precise detection of tetracycline, streptogramin and macrolide antibiotics in food samples. J Biotechnol. (2007) 128:668-880
- Broad-spectrum protein biosensors for class-specific detection of antibiotics. ELISA-based approach: Biotechnol Bioeng. (2005) 89:9-17
Combating drug-resistance in Mycobacterium tuberculosis
By synthetically reconstructing the control unit of the Mycobacterium tuberculosis ethionamide resistance determinant in human cells we developed a screening tool for the discovery of non-toxic, cell-permeable and target-specific antibacterial substances. We discovered that a fruit flavoring agent efficiently decreased resistance of M. tuberculosis against the drug ethionamide. Ongoing research pursues this approach to develop strategies to revert drug resistance in multi-drug-resistant human pathogenic bacteria.
- A synthetic mammalian gene circuit reveals anti-tuberculosis compounds. Proc Natl Acad Sci U S A. (2008) 105:9994-9998
- SwissTB Award 2009 http://www.swisstb.org/laureate/index.html
Signal-sensing and –transducing smart biomaterials
Using synthetic biology tools we develop smart biomaterials that respond to external stimuli by the release of therapeutic substances. Such smart biomaterials are currently under investigation as smart drug depot for the controlled release of therapeutic proteins in animals.
- Drug-sensing hydrogels for the inducible release of biopharmaceuticals. Nat Mater. (2008) 7:800-804.
- Stimuli-responsive hydrogels: drugs take control. Nat Mater. (2008) 7:767-768
bioss - Centre for Biological Signalling Studies / Arbeitgruppe Prof. Wilfried Weber
Forschung & Lehre