Latest SCI publications

Latest Projects

Research project (§ 26 & § 27)
Duration : 2023-01-01 - 2029-12-31

The vision of the CD laboratory is to move the production of rAAV for gene therapy from a cost-intensive, empirically-driven approach to a knowledge- and model-based process development and production. This requires a profound understanding of relationships such as target lines, therapeutic genes or process conditions interacting with one another and influencing the quality and quantity of rAAV. We will expand analyzes that allow accurate characterization of rAAV and contaminants. One of the most important tasks here will be the differentiation between therapeutic DNA-loaded and empty rAAVs, since different cell lines and different therapeutic genes lead to widely varying ratios between these variants. Product quality is currently being checked using post-process analysis. Such analyzes are time-consuming and costly, and require downtimes in the process. They only provide retrospective information and therefore cannot be used for process control. Therefore, sensors are being investigated that record important process parameters during the process and provide information about its course. This allows process monitoring and control, i.e. intervention in the process to ensure the desired quality. This approach not only increases the security of the processes, but also their efficiency. In order to develop a systematic understanding of important parameters and their interaction, different HEK target lines are examined and genome-wide analyzes of the cell response to virus production are carried out. Based on this, strategies to improve the rAAV yield and quality are developed. Scaling up optimized cell lines and processing strategies to production scale is a multi-step, time-consuming and costly process. The smallest scale currently available for the process development of rAAV production is the laboratory scale, which only allows a limited number of experiments due to the relatively high cost of materials. Only a miniaturized process development platform enables an integrated approach to investigate the relationships between process steps or upstream and downstream processing. This is therefore set up for the process development of rAAV and will include all relevant steps of cell cultivation and downstream processing. Finally, an optimized process is developed on this platform as an example and compared with a current process.
Research project (§ 26 & § 27)
Duration : 2020-08-01 - 2023-01-31

Sugar beet (Beta vulgaris ssp. vulgaris) is a young crop plant that originated from wild sea beet (Beta vulgaris ssp. maritima), a coastal plant native to Western and Southern Europe. It has been shown that transposons have influence onto the genome structure and gene functionality of beets. Of the many different repeats contained in a genome, only a small subset is intact and fully functional. However, this small portion may have a huge impact on the genome and as consequence on the phenotype as well. By creating alternative splicing patterns, introduction of novel promoters, change of gene regulation or simply by inactivation of gene function. Thus, the genome is constantly in motion: Transposons get inserted into new positions in the genome; thereafter, selection and mutational processes act upon them. Repeats disrupting crucial functions will disappear quickly, while other elements which are neutral or even beneficial will stay on. By comparing different genomic sequence data of domesticated beets and their wild relatives, we assess the mutagenic events that took place in the beet genome in the recent evolutionary past and explore the role that transposons have played in the evolution of the beet genome. Advances in the repeat-related knowledge of the beet genome may discover new insights about recent transposon evolution and will provide a foundation for further improvements of beet as a crop plant.
Research project (§ 26 & § 27)
Duration : 2021-09-01 - 2024-08-31

Theoretical framework One of the first specific defense mechanisms against invading pathogens and self-antigens is the complement system, activated by immunoglobulins (Igs). Igs bind specifically to the antigen on the pathogen and thereby enable the docking of the C1q-complement initiation complex. Two factors influencing the complement activation were so far not investigated in detail. First, the format of the antigen, described by the chemical nature, the molecular size and the mode of presentation (as soluble substance or embedded in vesicles for mimicking the cell surface). Second, the huge difference in complement activation resulting from the degree of oligomerization of the IgMs. Objectives The overall goal of the pent/hexIgM project is to elucidate the activation sites of C1q and the IgM-Fc after binding of pentameric and hexameric IgMs to different antigen formats. Approach/methods We will produce recombinant IgMs and the C1q protein in mammalian cells and generate mutants thereof by yeast surface display. Next, we will confirm the biological activities of generated proteins in vitro by immunochemical and biophysical analyses as well as functionality tests. Most important, we will elucidate in influence of the antigen format and the degree of oligomerization of the IgMs (pentameric versus hexameric IgMs) on the activation of the complement system. Level of originality Although IgMs in combination with complement proteins have an important function in the human body, these proteins are not yet widely used in therapy and diagnosis. The results of the pent/hexIgM project will contribute to understanding the complex mechanisms underlying the activation of the complement cascade and will provide data of particular importance for developing new diagnostics and efficient treatment methods for various infectious, inflammatory, chronical and cancerous diseases.

Supervised Theses and Dissertations