The goal of this project is to use the principles of synthetic biology for the creation of novel
functionalities in the interplay of DNA and proteins. We will devise high-throughput methods to
expand the chemical repertoire of DNA-binding protein scaffolds and develop screening techniques
to search for target functions in massive parallel fashion. We hope to discover novel, genetically
encodable DNA receptors that overcome limitations of natural protein scaffolds. Specifically, we will
introduce chemical functions that feature new or improved modes to recognize the information stored
in the sequence, chemical modification or conformation of DNA. Such receptors would represent
highly versatile tools to reengineer key biological processes that are based on DNA recognition
events. This could be achieved not only by binding to key DNA elements but also by using the
developed receptors as anchor entities to guide additional functionality - such as catalytic activity,
affinity tags or biophysical probes - to the locus of interest. Given the paramount role of DNA
recognition, this approach could lead to improved strategies in cancer drug development,
bioanalytics, genome engineering and gene therapy.
