Despite all progress, the development of fermentation processes with mammalian cells to a large extend is still based on empirical knowledge and historical experience and expertise. This is mainly due to missing qualitative and especially quantitative data and understanding of intracellular mechanisms under bioprocess conditions. Concomitantly there is an increasing economic and social interest in efficient processes for the production of biopharmaceuticals to ensure the supply of the public with modern, highly efficient and safe therapeutic and diagnostic proteins. In microbial research the combination of classical biotechnological methods with functional genomics and bioinformatics has led to substantial progress in the rational development of high-performance production strains and optimized fermentation processes. Due to the much higher complexity of mammalian cells these technologies have not been routinely applied in cell culture technology, although the potential of these methods has been shown in an increasing number of scientific publications.
In this context our group is working on the development and optimization of functional genomics techniques and their application in bioprocess and cell line development using CHO and human cell lines. This includes genome sequencing of cell lines, epigenetics (DNA methylation and histone modifications), transcriptomics (RNAseq), proteomics (cellular and phosphoproteome using SILAC and label-free quantification), substrate and metabolite analysis and glycoanalysis of recombinantly expressed proteins.
We use these methods to understand bioprocesses and cellular behavior on a molecular level to develop optimized fermentation processes and cell lines. Prospectively we are especially interested in different aspects of heterogeneity in cell culture processes. This will address the following questions: