Our inspiration is the ability of organisms and the materials they are made of to adapt to dynamic environmental conditions. Plants adapt growth to light conditions; bacteria develop resistance against antibiotics or bones get stronger when exercised. The basis for this ability to adapt is a fascinating information processing machinery of the organisms: Environmental conditions are captured by molecular sensors, then the signals are processed and integrated with genetic programs to finally yield a targeted response.
In our research, we engineer nature’s molecular sensing, processing, and actuation machinery in order to precisely control the function and properties of cells and materials. We apply these newly developed technologies in different fields of fundamental and applied research.
Stimulus-responsive and Information-processing (living) Materials
We develop and apply stimulus-responsive and information-processing biohybrid polymer materials. To this aim, we functionally couple synthetic biological molecular sensors and switches to polymer materials. By wiring these switches according to topologies inspired by electronic circuits, we engineer materials that perform fundamental computational operations. Examples of our work include:
- We engineered a hydrogel based on a bacteria-derived photoreceptor which allows the light-responsive, fully reversibly tuning of its mechanical properties. We applied this hydrogel as extracellular matrix to analyze the impact of dynamic mechanical environments on transcriptome-wide responses in mesenchymal stem cells or on the migration of T-lymphocytes.
See Hörner et al. Advanced Materials 2019
- We integrated synthetic biological switches with polymer materials into a circuit inspired by an electronic counter. The resulting material system was able to count the number of input light pulses and to release different output as a function of the number of light pulses detected. We applied this system to sequentially release different biocatalysts to drive a two-step biochemical reaction.
See Beyer et al., Advanced Materials 2018
- We developed chemically responsive hydrogels and wired them in positive feedback and feedforward topologies where the output of one gel served as input for the others. Guided by a mathematical model, we configured the materials system to serve as signal amplifier for the sensitive detection of antibiotics, enzymes, or toxins.
See Wagner et al., Materials Today 2019 and Wagner et al., Advanced Science 2018
- We developed PenTag, a protein tag for the spontaneous, covalent coupling of proteins to ampicillin-functionalized molecules such as dyes, polymers, or solid supports. Based on this strategy, we engineered and assembled material modules to function as encoder for processing different combinations of biochemical input stimuli.
See Mohsenin et al., BioRxiv 2023
We develop and apply molecular optogenetic tools to control cell fate and function with unprecedented spatial and temporal precision in a dose-dependent and highly specific manner. To this aim, we engineer plant- and bacteria-derived photoreceptors and functionally couple them to proteins involved in cell signaling and gene expression. Examples of our work include:
- Orthogonal control of the expression of three genes within a mammalian cell in response to light of three different colors.
See Müller et al., Nucleic Acids Research 2013
- Light-inducible formation of liquid transcription factor condensates in mammalian cells and mice. These “transcription factor droplets” were shown to be several-fold more active in inducing transgene expression compared to normal transcription factors.
See Schneider et al., Science Advances 2021
- Light-guided adeno-associated viral (AAV) vectors. We engineered a light-responsive tropism into AAVs which allows us to selectively transfer genetic information into single cells or to transduce different cells within one culture with different transgenes.
See Hörner et al., Science Advances 2021
Our group is running www.optobase.org, the most comprehensive database on molecular optogenetics. Have a look and discover the amazing opportunities in controlling biology with light!
We integrate natural and engineered molecular sensors for drugs, metabolites or nucleic acids into suitable readout formats for the fast and sensitive quantification of such substances. Together with collaboration partners, we develop biosensor systems for different application fields: