A5051883867- Microbial Metabolic Engineering and Bioproduction
- Viral Infectious Diseases and Gene Expression in Insects
- RNA and protein synthesis mechanisms
- Bacterial Genetics and Biotechnology
- Gene Regulatory Network Analysis
- Protein Structure and Dynamics
- thermodynamics and calorimetric analyses
- CRISPR and Genetic Engineering
- Bioinformatics and Genomic Networks
- Origins and Evolution of Life
- Enzyme Structure and Function
- Glycosylation and Glycoproteins Research
- Biofuel production and bioconversion
- RNA modifications and cancer
- Virology and Viral Diseases
- Advanced Control Systems Optimization
- Enzyme Production and Characterization
- Metabolomics and Mass Spectrometry Studies
- Supercapacitor Materials and Fabrication
- Protein purification and stability
- Advancements in Battery Materials
- ATP Synthase and ATPases Research
- Fungal and yeast genetics research
- Advanced Battery Materials and Technologies
- Polyamine Metabolism and Applications
University of Vienna
2020-2024
Austrian Centre of Industrial Biotechnology (Austria)
2018-2021
BOKU University
2020
Comenius University Bratislava
2016
Cell line-specific, genome-scale metabolic models enable rigorous and systematic in silico investigation of cellular metabolism. Such have recently become available for Chinese hamster ovary (CHO) cells. However, a key ingredient, namely an experimentally validated biomass function that summarizes the composition, was so far missing. Here, we close this gap by providing extensive experimental data on composition 13 parental producer CHO cell lines under various conditions. We report total...
Genome-scale metabolic models (GSMMs) offer a holistic view of biochemical reaction networks, enabling in-depth analyses metabolism across species and tissues in multiple conditions. However, comparing GSMMs Against each other poses challenges as current dimensionality reduction algorithms or clustering methods lack mechanistic interpretability, often rely on subjective assumptions. Here, we propose new approach utilizing logisitic principal component analysis (LPCA) that efficiently...
Following the success of and high demand for recombinant protein-based therapeutics during last 25 years, pharmaceutical industry has invested significantly in development novel treatments based on biologics. Mammalian cells are major production systems these complex biopharmaceuticals, with Chinese hamster ovary (CHO) cell lines as most important players. Over various engineering strategies modeling approaches have been used to improve microbial platforms, such bacteria yeasts, well create...
Abstract Ribosomes are key to cellular self-fabrication and limit growth rate. While most enzymes proteins, ribosomes consist of 1/3 protein 2/3 ribonucleic acid (RNA) (in E. coli ). Here, we develop a mechanistic model self-fabricating cell, validated across diverse conditions. Through resource balance analysis (RBA), explore the variation in maximum rate with ribosome composition, assuming constant kinetic parameters. Our highlights importance RNA instability. If neglect it, synthesis is...
ABSTRACT HEK293 cells are a versatile cell line extensively used in the production of recombinant proteins and viral vectors, notably Adeno-associated virus (AAV) [12]. Despite their high transfection efficiency adaptability to various culture conditions, challenges remain achieving sufficient yields active particles. This study presents comprehensive multi-omics analysis two strains under good manufacturing practice focusing on metabolic cellular responses during AAV production. The...
Traditional (genome-scale) metabolic models of cellular growth involve an approximate biomass “reaction”, which specifies composition in terms precursor metabolites (such as amino acids and nucleotides). On the one hand, is often not known exactly may vary drastically between conditions strains. other predictions computational crucially depend on biomass. Also elementary flux modes (EFMs), generate cone, reaction. To better understand phenotypes across conditions, we introduce analyze new...
Chinese hamster ovary (CHO) cells are the leading platform for production of biopharmaceuticals with human-like glycosylation. The standard practice cell line generation relies on trial and error approaches such as adaptive evolution high-throughput screening, which typically take several months. Metabolic modeling could aid in designing better producer lines thus shorten development times. genome-scale metabolic model (GSMM) CHO can accurately predict growth rates. However, order to...
Chinese hamster ovary (CHO) cells are the most popular mammalian cell factories for production of glycosylated biopharmaceuticals. To further increase titer and productivity ensure product quality, rational system-level engineering strategies based on constraint-based metabolic modeling, such as flux balance analysis (FBA), have gained strong interest. However, quality FBA predictions depends accuracy experimental input data, especially exchange rates extracellular metabolites. Yet, it is...
Overflow metabolism is a well-known phenomenon that describes the seemingly wasteful and incomplete substrate oxidation by aerobic cells, such as yeasts, bacteria, mammalian even when conditions allow for total combustion via respiration. This cellular response, triggered an excess of C-source, has not yet been investigated in archaea. In this study, we conducted chemostat cultivations to compare metabolic physiological states thermoacidophilic archaeon Sulfolobus acidocaldarius under three...
Abstract Chinese hamster ovary (CHO) cells are the leading platform for production of biopharmaceuticals with human-like glycosylation. The standard practice cell line generation relies on trial and error approaches such as adaptive evolution high-throughput screening, which typically take several months. Metabolic modeling could aid in designing better producer lines thus shorten development times. genome-scale metabolic model (GSMM) CHO can accurately predict growth rates. However, order...
Abstract Background Chinese hamster ovary (CHO) cells are the most popular mammalian cell factories for production of glycosylated biopharmaceuticals. To further increase titer and productivity ensure product quality, rational systems-level engineering strategies based on constraint-based metabolic modeling, such as flux balance analysis (FBA), have gained strong interest. However, quality FBA predictions depends accuracy experimental input data, especially exchange rates extracellular...
Abstract Traditional (genome-scale) metabolic models of cellular growth involve an approximate biomass “reaction”, which specifies composition in terms precursor metabolites (such as amino acids and nucleotides). On the one hand, is often not known exactly may vary drastically between conditions strains. other predictions computational crucially depend on biomass. Also elementary flux modes (EFMs), generate cone, reaction. To better understand phenotypes across conditions, we introduce...
Abstract Ribosomes are protein synthesis machines that central to cellular self-fabrication, and the time of a ribosome places an upper bound on growth rate. While most enzymes proteins, ribosomes consist 1/3 2/3 RNA (in E. coli ). Recent research suggests composition arises from trade-off between two “autocatalytic loops”, ribosomal polymerase synthesis, respectively. In this study, we develop (coarse-grained) mechanistic model self-fabricating cell validate it under various conditions....
Abstract Genome-scale metabolic models (GSMMs) offer a holistic view of biochemical reaction networks, enabling in-depth analyses metabolism across species and tissues in multiple conditions. However, comparing GSMMs against each other poses challenges as current dimensionality reduction algorithms or clustering methods lack mechanistic interpretability, often rely on subjective assumptions. Here, we propose new approach utilizing logisitic principal component analysis (LPCA) that...