Expertise:

Proteomics, PTMomics, bioinformatics for the processing of biological mass spectrometry data, cell culture techniques, in vitro models, cellular metabolism, systemic and molecular alterations in cardiac and cardiometabolic pathology

Background in chemical engineering, analytical chemistry, and biotechnology/molecular biology, with additional expertise and affiliations in nutritional and medical sciences. 

PhD project: Host cell omics effects of therapeutic protein process parameters, Mass Spectrometry-based Characterization of Mammalian Cell Metabolism

To meet the growing demand for biotherapeutics employed today, producer cell lines are under ever-constant development to improve their productivity, stability and product quality. Chinese hamster ovary (CHO) cells are the leading cellular factories for producing recombinant proteins in the pharmaceutical industry due to their capability to perform efficient human-like post-translational modifications. Still, only little is known about the effect of bioprocess parameters on critical quality attributes (CQAs). 

“Big data” approaches, such as multi-omics-based characterization of cellular functions, show great potential in aiding academic and industrial efforts to improve the mechanistic understanding of how host cell changes in metabolism and other cellular pathways affect productivity and product quality. The utilization of integrated, state-of-the-art host cell-omics to supplement conventional, medium-based measurements offers the elucidation of producer CHO cell lines and the interrelation of crucial process parameters (CPPs) during cultivation and molecular CQAs (e.g. glycosylation patterns) of the protein product.

Our project, “DigitherapeutX, opens an external URL in a new window”, spanning multiple universities with each respective working group offering distinct key competencies, aims to deeply characterize the bioprocess of protein biotherapeutic production in CHO producer cell lines. For this, multiple fed-batch fermentations of varying, e.g. feeding strategies, temperature shifts, or feed composition, will be carried out. By simultaneous monitoring of CQAs and PPs, including host cell biological functions, mathematical models predicting the effects of bioprocess parameters on the desired quality attributes can be built, tested and deployed. Such models may drive the understanding of quality-ensured bio-manufacturing, allow immediate adjustments during the bioprocess, and eventually lead to improved and predictable biotherapeutic yield, quality, safety, and efficacy.

As part of this dissertation project, a fast, representative, and highly applicable sampling approach for suspension cultures that allows for multi-omics characterization of cellular functions will be developed. This further includes the evaluation and adaptation of state-of-the-art sample preparation and mass spectrometry-based analysis workflows suitable for the nature of the respective samples and analytes. As accurate analysis of protein expression and post-translational modification (PTM) of proteins such as reversible phosphorylation can effectively decipher vital cellular processes and their regulation, particular focus in addition to proteomics will be on implementing PTMomics as deemed fit. Furthermore, a targeted approach for the efficient and reproducible analysis of intracellular metabolites will be established. Additionally, options for assessing the secretome from the medium will be explored. Omics results will be integrated into the parallel monitoring of cell proliferation and viability, as well as nutrient consumption and metabolic by-products, to achieve a comprehensive characterization of cellular functions throughout the bioprocess to allow for the realization, testing and validation of bioprocess mathematical models. 

A mass spectrometry-based multi-omics method can offer an in-depth analysis of cellular functions in various product and process-relevant biological settings. The advanced characterization of producer cell line(s) will drive research in recombinant protein production and bioprocess engineering.