1 PhD position in E. coli Metabolism under Dynamic Production Conditions in Netherlands | Delft University of Technology (TU Delft)

Microbial metabolism and its performance are highly dependent on environmental conditions. The ability of cells to adjust their metabolism in response to varying environmental conditions is essential for their survival in ecological systems but also in the production bioreactor environment. In particular, large-scale imperfect mixing leads to gradients in substrate and oxygen availability that influence microorganism performance. Effects observed vary from improved productivity to significant reductions. Different hypotheses for the impact of dynamics have been formulated, including:

• population heterogeneity and/or
• bioreactor inhomogeneity and associated oscillatory conditions.

On a phenotypic level, both aspects can be associated with a ‘training effect’ showing the flexible metabolic and regulatory adaptation to handle dynamic conditions by fine-tuned (rapid) flux re-distribution. In the project, the production strain is analysed using state-of-the-art metabolomics and fluxomics technologies. In particular, scale-down approaches will be used to mimic large-scale bioreactor substrate and oxygen supply variations. Modern targeted and non-targeted metabolomics methods are used to unveil the metabolic response in vivo. 13C tracer technologies are applied to follow the intracellular metabolic dynamics with the aim of resolving the intracellular reaction rates, including parallel and cyclic pathways. Differences between ‘trained’ and ‘untrained’, ‘producing’ and ‘non-producing’ microorganisms are revealed by cultivations with isotopically labeled substrates.

Requirements

The candidate should have:

• a Master degree in biochemical engineering/biotechnology or a related background.
• a strong background in mathematical modelling of cellular systems.
• the ability to work in a multi-disciplinary team.

Conditions of employment

TU Delft offers an attractive benefits package, including a flexible work week and the option of assembling a customised compensation and benefits package. Salary and benefits are in accordance with the Collective Labour Agreement for Dutch Universities. As a PhD candidate you will be enrolled in the TU Delft Graduate School. TU Delft Graduate School provides an inspiring research environment; an excellent team of supervisors, academic staff and a mentor; and a Doctoral Education Programme aimed at developing your transferable, discipline-related and research skills.

Organisation

Delft University of Technology (TU Delft) is a multifaceted institution offering education and carrying out research in the technical sciences at an internationally recognised level. Education, research and design are strongly oriented towards applicability. TU Delft develops technologies for future generations, focusing on sustainability, safety and economic vitality. At TU Delft you will work in an environment where technical sciences and society converge. TU Delft comprises eight faculties, unique laboratories, research institutes and schools.

Department

Applied Sciences

The Department of Biotechnology engages in internationally leading education programmes and ground-breaking research as a basis for scientific, technological and societal innovation in industrial and environmental biotechnology.

The Cell Systems Engineering group aims at improving the efficiency of bioprocesses by focusing on microbial performance. Knowledge of the metabolism of microbial cells is indispensable for (a) the optimisation of bioreactor operation, (b) the selection of the best micro-organism for a given biochemical conversion, (c) targeted or evolutionary improvement of an existing micro-organism and (d) design (metabolic engineering) of micro-organisms with new reactivities and/or morphology. The group has broad experience in wetlab experiments and modelling of metabolic networks.