The focus of our group is recombinant protein production using mammalian expression systems.
Our research mainly centers on the following topics:
- Establishment and selection of production cell lines for recombinant proteins
- Upstream process development and optimization in bioreactors
- Examination of the bioproduction process to control product quality attributes
- Research on and manipulation of cell physiology and expressed protein
Recombinant production cell lines
The value of recombinant proteins is constantly rising in health management and the development of human therapies. Therefore, a significantly growing demand for therapeutic proteins exists. We are employing and improving host cell lines, expression vectors and selection strategies for clone development and are investigating the influence of growth media and other environmental conditions for process optimization on various recombinant cell lines. With our research, we aim to establish a broader insight into factors influencing the production pathway and we are analyzing incidences in the production cell line induced by the expression of recombinant proteins. For this purpose, we have an abundant cell bank with numerous recombinant and host cell lines including CHO (DUKX, DG44, K1, S), NS0, HEK, Vero, hybridoma etc. The list of developed expression clones includes various subclasses of antibodies (IgG, IgA, IgM, IgE), synthetic antibody constructs (scFv-Fc, Fab), cytokines, hormones and fusion proteins (EpoFc).
Cell culture technology has matured considerably in the last decades and evolved into a relatively reliable and robust technology. Still, there are a number of steps to be optimized that synergistically contribute to the successful exploitation of this technology and production of a given recombinant protein at high quantity and desired quality. Constantly monitoring and controlling the environmental conditions in bioreactors allows us to understand and improve bioproduction processes.
General biology of cells
The origin of the host cell line essentially influences the physiology of recombinant cells but also changes during the course of selection and contributes to metabolic properties of the final producer clones. Recombinant protein expression is mainly determined by (1) genetic stability and the chromosomal environment; (2) mRNA stability and processing; (3) translation, maturation and secretory events which are altogether responsible for a balanced cellular physiology. Our aim is to accumulate information and draw proper conclusions to better understand the impact of changes occurring during batch production and factors influencing this process to maximize the product formation efficiency of mammalian cells.
Molecular design of expressed proteins
Advanced empirical knowledge in combination with molecular modelling and simulation of antibodies have provided the basis for a deeper understanding of antigen/antibody interaction and their specificity and functionality. We are also investigating the influence of humanization approaches on the specificity and the expression potential of monoclonal antibodies. Optimal combination of state-of-the-art in-silico and in-vitro techniques enables us to develop novel concepts for molecular antibody engineering and to define the structure/function relationship of antibodies together with their impact on folding and secretion capabilities within mammalian cell factories.