Transcriptional control of high cell density phenotypes

Abstract:

Advanced cell factory design and development concepts rely on accurate prediction and control of cellular phenotypes during a microbial cultivation. However, cellular engineering often ends up in re-wiring not only the metabolic network but also the inherent regulatory feedback and control properties of the cell. As a result, under uncertain environmental conditions cellular robustness plays a decisive role in maintaining cellular homeostasis, often leading to cellular variability in a production setting.

In this talk, the co-ordinated high cell density regulatory response of Escherichia coli when exposed to intrinsic (e.g., with genetic variations) and extrinsic multiple environmental conditions (i.e., relevant industrial-scale heterogeneities) will be presented. The study is based on massive (more than 500) high-quality controlled bioreactor cultivation data (nutrient uptake and production profiles) and condition-dependent transcriptional response data (more than 600 RNA-seq. profiles) generated using AMBR250® bioreactor system. The data generated have been logged according to FAIR-based principles, facilitating machine learning models to accurately map cell-density dependent transcriptional signatures.

The mapped cell-density based transcriptional and phenotypic response was helpful to understand various traits of high cell density cultivation. Subsequently, such mapping would enable integral feedback control strategies of cells which translate the extracellular signals into specific intracellular responses to cope with new conditions; thereby enhancing our current baseline understanding of cellular senseome for sustainable bio-based production solutions.

Speakers: Dr. Suresh Sudarsan finished his MSc degree in Chemical Engineering and received his PhD from the Department of Bio & Chemical engineering from TU Dortmund, Germany. After 4 years of postdoc period in RWTH Aachen University, Germany, he moved to Denmark (in 2016) to get trained as a Bioprocess engineer at the Novo Nordisk Foundation Center for Biosustainability in Denmark Technical University (DTU). Since 2021, he is working as a Senior Program Manager for the High Density Physiologic program, aiming at understanding the scale-dependent, environment specific insight of microbial metabolism by a combination of three different approaches, i.e. Biological understanding, Bioprocess engineering and Biological engineering.