© Universität Bielefeld
Cellular and Molecular Biotechnology Group
The Cellular and Molecular Biotechnology group under the guidance of Prof. Kristian M. Müller aims at engineering biomolecules and cells for clinical and industrial applications. We use means of genetic engineering and protein engineering in combination with synthetic biology approaches to create and deploy directed evolution, cellular bio-production devices, and ultimately next generation bio-pharmaceuticals. These application driven goals are accompanied by basic research aspiring to unravel the principles of biological systems based on their chemical and physical properties.
Currently we focus on three research areas: i) recombinant adeno-associated viruses for gene-based prodrug-activation therapy of cancer, ii) site specific modification of antibodies for the generation of antibody-drug conjugates, and iii) development of selection and directed evolution technologies.
In the advent of the patient-omics age, targeted and personalized medicine is on the rise. To fulfill the promises of these advanced approaches, basic research and technology need to advance at the same time. With our basic research, we illuminate the intricate paths from genes to a multi-component biopharmaceutical as well as the complex patterns governing the multi-modal interaction of targeted biopharmaceuticals with cells. This knowledge is used to devise new production technologies and generate therapeutic efficacy beyond the current state of the art.
We rationally engineer the tropism of recombinant adeno-associated viruses (rAAV) with genetically encoded protein and peptide fusions to the capsid proteins and modify the gene of interest containing vector plasmid for cell-specific transcription and translation. Production of these virus-like particles is scaled up in collaboration with the cell culture technology group of Prof. Thomas Noll (Bielefeld) and local biotech companies.
The antibody drug conjugate (ADC) research is conducted in collaboration with the biochemistry group of Prof. Thomas Dierks (Bielefeld) and the organic chemistry group of Prof. Norbert Sewald (Bielefeld). We use a bio-orthogonal, chemo-enzymatic approach in which genetically fused peptide-tags are modified by formyl-glycine generating enzymes (FGE) and subsequently coupled with reporter or cytotoxic small molecules. Antibody constructs are produced in CHO cells and analyzed with various cell lines expressing the tumor marker EGFR.