Advanced Course

Microbial Physiology and Fermentation Technology

Course description

This very successful course will be held in 2022 for the 33th time! The course aims to familiarize participants with the integrated, interdisciplinary approach required in modern biotechnology. Microbial physiologists, metabolic engineers and (bio)process engineers from the faculty staff, together with invited (inter)national experts from other universities and industry, will offer a combination of lectures, exercises and demonstration experiments. In this way, the course will present an intensive and in-depth treatment of the state of the art. At the same time, the course provides the necessary link between, on one hand, fundamental subjects (e.g. stochiometry/kinetics of metabolic networks, physiology/systems biology) and, on the other hand, applications for design of microorganisms and and optimization of large-scale biotechnological processes.

17 – 28 January 2022

Delft University of Technology, the Netherlands

A limited number of fellowships is available for PhD students (reduced fee).


Advanced Course Microbial Physiology and Fermentation Technology

For a better understanding of the lectures and to enhance active participation, this intensive two-weeks course consists of lectures, practical demo’s, computer simulations, exercises and case studies.

Morning and evening

course_Microbial-PhysiologyThe lectures are mainly scheduled in the mornings and the early evenings. In the lectures, attention will be paid to the following themes:

  • Energy transduction and growth thermodynamics
  • Kinetics and stoichiometry of growth and product formation
  • Regulation of metabolism by environmental parameters
  • High-cell density fermentation
  • Metabolic networks: stoichiometry and fluxes
  • Rate based design
  • Regulation and control of metabolic fluxes
  • Metabolic engineering
  • Heterogeneity and mixed cultures
  • Capita selecta


Demo’s in fed-batch fermentation. Discussions and interpretation of results. On- and off-line measurements in the gas and liquid phase of reaction parameters and determination of the kinetics of biological conversions. Statistical data processing using mass balances. Tutorials in setting-up and simulating computer models of metabolic networks. Introduction to methods for upscaling. Possibilities to visit the research projects of the Biotechnology Department.

Study load

The course (including preparatory materials) is valued 98 hours of work.

Who should attend?

This Advanced Course is aimed at professionals (MSc, PhD or equivalent experience) in microbiology, biochemistry or biochemical engineering with a basic working knowledge of the two other disciplines. Also, molecular biologists with a microbial background may apply. The course is primarily aimed at those already employed in industry who wish to up-date their theoretical knowledge and practical insight in this field. In addition, this Advanced Course is an option in the two-year postgraduate programs of Delft University of Technology.

Course registration

Please register clicking the tab Register to attend the course. Applicants will be handled in order of the date of receipt.


Programme 2022:

Monday, 17 January 2022
Theme: Thermodynamics, balances and q-rates
08.30 Registration
09.00 Outline of the course Han de Winde
09.15 Basic energetics of microbial metabolism Robbert Kleerebezem
10.30 Balances Sef Heijnen
11.30 q-rates Sef Heijnen
12.15 Lunch
13.15 Parallel sessions:
Exercises on energetics of microbial metabolism

Exercises on balances and q-rates

Sef Heijnen

Robbert Kleerbezem

17.30 Social drink and buffet
Tuesday, 18 January 2022

Theme: Kinetics and stoichiometry of growth, product formation, process design and membranes transport

09.00 Batch, fed batch and continuous cultivation Aljoscha Wahl
10.15 Black box model: kinetics / parametrization Sef Heijnen
11.30 Black box model: stoichiometry Sef Heijnen
12.30 Lunch
13.30 Introduction to bioprocess design (batch, continuous) Sef Heijnen
14.30 Exercises on bioprocess reactions in design
17:45 Transport over biological membranes: mechanisms and thermodynamics Walter van Gulik
18.30 End of the day
Wednesday, 19 January 2022

Themes: Regulation of metabolism by environmental parameters, fermentation design and data analysis

09.00 Primary metabolism and its regulation Pascale Daran – Lapujade
10.00 Microbial growth with mixtures of carbon substrates Han de Winde
11.00 Physiological aspects of high cell density fermentation Han de Winde
12.00 Lunch
13.00 Fed-batch fermentation and transport phenomena Sef Heijnen
14.30 Exercises on data analysis of fermentation processes Sef Heijnen
17.00 Optional: Lab techniques tour at the department of Biotechnology followed by a drink
18.00 End of the day
Thursday, 20 January 2022

Theme: Metabolic networks: stoichiometry, Flash energy and Fed batch demo

09.00 Metabolic network analysis Walter van Gulik
10.00 Exercises: Metabolic pathway stoichiometry Walter van Gulik
12.30 Lunch
13.30 Fed-batch demo (1): Stoichiometry network calculation and fed batch fermentation Sef Heijnen
14.30 Fed-batch demo (2): Design calculations and measurements why and how Rob Kerste
16.00 Bioenergetics of microbial growth and the cost of adaptation Joost Teixeira de Mattos
18.00 Buffet
Friday, 21 January 2022

Theme: Metabolic networks: stoichiometry, fluxes and high-cell density fed batch

09.00 Metabolic flux balancing: theory and applications Aljoscha Wahl
10.15 Computer exercises on metabolic network analysis Aljoscha Wahl
12.45 Lunch
13.45 Metabolic studies in the industrial contexts Ralf Takors
14.45 Exercises on high cell density fed-batch cultivation Walter van Gulik
18.15 Social drink
Monday, 24 January 2022

Theme: Case study – Ethanol from syngas

09.00 Rate based design of biosystems Sef Heijnen
09.30 Case study introduction: Ethanol from syngas Henk Noorman / Sef Heijnen
12.45 Lunch
14.00 Continuation of Case study Henk Noorman / Sef Heijnen
17.15 Gas Fermentation: a path to low carbon fuel and chemical production with impact Bjorn Heijstra
Tuesday, 25 January 2022

Theme: Regulation and control of metabolic fluxes, rapid sampling

09.00 Multi-scale modelling of process dynamics in large-scale bioreactors Matthias Reuss
10.15 Multi-level regulation of metabolic fluxes, transcripts versus fluxes Pascale Daran – Lapujade
11.00 Analysis of in vivo kinetics: rapid sampling and metabolite analysis Walter van Gulik
12.15 Lunch
13.15 Fed-batch demo (3): balance calculations on batch phase data Sef Heijnen / Dirk Geerts / Rob Kerste / Walter van Gulik
15.15 Antonie van Leeuwenhoek: his work and his microorganisms Lesley Robertson
16.00  Van Leeuwenhoek and Delft: a microbiological pilgrimage Lesley Robertson
18.00 Drink and snacks
Wednesday, 26 January 2022

Theme: Metabolic and community engineering

09.00 Monascus ruber as cell factory for lactic acid production at low pH Ruud Weusthuis
10.15 Evolutionary and reverse engineering of S. cerevisiae Robert Mans
11.30 Microbial community engineering for production of chemicals and bioenergy Robbert Kleerebezem
12.30 Lunch
13.30 From System Biology to Metabolic Engineering and Industrial Process Development using Clostridium acetobutylicum as a
Platform Strain
Philippe Soucaille
14.45 Metabolic engineering strategies for reducing costs Sef Heijnen
16.00 Exercises on metabolic engineering strategies for reducing costs Sef Heijnen
18.00 End of the day
Thursday, 27 January 2022

Theme: Heterogeneity of microbial populations

09.00 Single cell studies of micro-organisms / Microfluidics Sander Tans
10.15 Spatio-temporal single-cell analysis in picoliter reactors Dietrich Kohlheyer
11.30 The limits to growth: the challenge to dissipate energy Matthias Heinemann
12.30 Lunch
13.30 Transcription factor-based biosensors for strain development Jan Marienhagen
15.30 Fed-batch demo (4): balance calculations on the fed phase data and evaluation Sef Hejnen / Dirk Geerts / Rob Kerste / Walter van Gulik
19.00 Course dinner
Friday, 28 January 2021

Theme: Capita Selecta

09.30 Microbial protein production in an industrial context Cees Sagt
10.45 Systems Bioengineering for commodity chemicals Stefan de Kok
11.45 Lunch
13.15 Latest advancements in high-resolution microbial mass spectrometry Martin Pabst
14.45 The origin of life and metabolism John Sutherland
16.00 Farewell drink

The course will be held at:

Faculty of Applied Sciences (building 58)
Department of Biotechnology
Delft University of Technology
Van der Maasweg 9
2629 HZ Delft
The Netherlands
P +31 (0)15 278 1922
F +31 (0)15 278 2355


Deadline for registration is 27 December 2021

The course fee is:

Early Bird €3650,-*
Regular Fee €3900,-
PhD Students €1825,-**

*To be eligible for the reduced early bird fee you need to register before 8th of November 2021. If this date is exceeded, the regular fee applies.

**A limited number of fellowships is available for PhD students. To apply, please include a copy of your registration as a PhD student from your university.

The fee includes course materials, lunches and the buffets and the course dinners as indicated on the program. The fee does not cover other meals or lodging. Hotel accommodation can be arranged at your request.

The course fee is preferably paid by bank transfer. Payment by PayPal is possible. TU Delft employees can use their internal (project) code.

Preparatory texts will be sent one month before start of the course and after receipt of the course fee. The complete set of course books will be supplied at the start of the course.

In the event of your cancellation before 22 November 2021, a full refund will be granted. After this date, a 25% fee charge can be made.

Delay of payment past the final deadline as indicated on the invoice may result in cancellation of entry to the course. Re-entry is only possible in case of vacancies and the regular fee will be applied. Payment terms and deadlines will be indicated on the invoice and/or provided in an e-mail after registration, but the course fee should always be paid before the start of the course.

When the number of participants is too low to have a fruitful course, the Institute BioTech Delft will cancel the event no later than six weeks before the start of the course. The course fee will be reimbursed within three weeks after cancellation. In case a speaker will not be able to present his/her lecture, due to unforeseen circumstances, BioTech Delft will arrange an equivalent replacement.


Course board

Prof. Sef Heijnen

After his MSc studies in Chemical Engineering, Sef Heijnen worked at DSM (then: Gist Brocades) for 15 years and in this period he also completed his PhD thesis in bioprocess technology at Delft University of Technology. In 1988, he became full professor and group leader in Cell Systems Engineering within the Department of Biotechnology of Delft University of Technology. He has an impressive track record: he is (co-) author of over 400 scientific publications, has supervised 50 PhD students and is a member of the Royal Netherlands Academy of Arts and Sciences (KNAW). His research interests are (1) metabolic engineering and systems biology applied to industrial microbial processes using Saccharomyces cerevisiae, Penicillium chrysogenum and Escherichia coli, (2) metabolome measurement and 13C-tracer analysis in steady state and dynamic conditions, and (3) thermodynamic and kinetic modelling of metabolism and fermentation. Prof. Heijnen teaches a wide variety of courses, and was elected at TU Delft’s 2003 ‘Leermeester’ (best lecturer).

Prof. Han de Winde

Han de Winde holds an MSc in organic chemistry and biochemistry from the Vrije Universiteit of Amsterdam, and a PhD in molecular biology from the University of Amsterdam. He was NWO postdoctoral research fellow at the Amsterdam BioCenter and EU-HCM fellow and assistant professor at the Laboratory of Molecular Cell Biology, Catholic University of Leuven, Belgium. In 2000 he was appointed Senior Scientist Genetics & Physiology at DSM Bakery Ingredients. From 2002 he became full professor in Industrial Genomics, at TU Delft and from 2004 Principal Scientist Microbial Genetics and Physiology at DSM Food Specialties RD&T. From 2006 Han was Scientific Director at the Department of Biotechnology, TU Delft. He was business director of the Kluyver Center for Genomics of Industrial Fermentation (NWO-NGI Dutch National Centre of Excellence), and scientific director of the Delft Research Centre for Life Science and Technology (DRC-LST), and of the Graduate Research School ‘Biotechnological Sciences Delft-Leiden’ (BSDL (now: BioTech Delft)). Since April 2013 Han de Winde is vice dean, Faculty of Sciences, at Leiden University and chairholder of Industrial Biotechnology at the Leiden Institute of Biology.

Han de Winde has obtained thorough expertise in research, development and education at BSc, MSc, PhD and advanced level. His scientific expertise is in microbial molecular genetics and metabolic engineering, specifically in the area of nutrient- and environment-induced signal transduction and control of physiology, growth and development of bacteria, yeast and fungi. He is expert in implementation and development of applied functional genomics and systems biology in microbial strain and process improvement. He is (co)author of over 85 peer reviewed scientific publications and of 10 filed patents families.

Faculty staff

Dr. Pascale Daran-Lapujade

Pascale Daran-Lapujade is assistant professor at the TU Delft Department of Biotechnology in the Industrial Microbiology section. Her research investigates the physiology of the yeast Saccharomyces cerevisiae, to unravel the molecular mechanisms that drive its response to diverse environmental stimuli and to identify the evolutionary circumstances that have shaped their genomes. Although many of her research questions are inspired by industrial applications of yeasts, she also seeks to contribute to a deeper understanding of fundamental aspects of cellular physiology and metabolism, using S. cerevisiae as a model. In addition she is editor of the journal FEMS Yeast Research and member of the board of the Microbial Biotechnology section of the Dutch Society for Microbiology (KNVM).

Dr. Walter van Gulik

Delft University of Technology, Cell Systems Engineering, Delft, the Netherlands

Ir. Robert Mans

Robert Mans has completed his degree as a master of science in 2012 in the study of Life, Science & Technology. In his thesis research he has focused on yeast physiology and both metabolic and evolutionary engineering. He is currently working as a PhD student in the Industrial Microbiology group under the supervision of Ton van Maris, Jean Marc Daran and Jack Pronk, where he focusses on free energy (ATP) conservation in S. cerevisiae. Of specific interests to him are evolutionary engineering, cloning techniques and yeast physiology.

Dr. Robbert Kleerebezem

Delft University of Technology, Environmental Biotechnology, Delft, the Netherlands

Dr. Aljoscha Wahl

Aljoscha Wahl is assistant professor at TU Delft with a focus on fluxomics and metabolomics in eukaryotic microorganisms. He studies the interactions of metabolism and its regulation under dynamic environmental conditions. Dr. Wahl contributes to experimental and computational approaches for (1) 13C flux analysis under metabolic dynamic conditions, (2) compartmentalized fluxomics and metabolomics using intracellular sensor reactions, (3) transport system studies.  He teaches several master courses at TUD and was active in the iGEM competition (supervisor of the TUD team and organization of the European Jamboree). In addition, he is member of the editorial board of Applied and Environmental Microbiology (AEM)

Coordinators Fed-batch demo

Dirk Geerts

Delft University of Technology, Cell Systems Engineering, Delft, the Netherlands

Guest lecturers

Prof. Matthias Heinemann

University of Groningen, Molecular Systems Biology Group, Groningen, the Netherlands

Mickel Jansen

DSM Biotechnology Center, Delft, the Netherlands

Dr. Dietrich Kohlheyer

Institute of Bio- and Geosciences, IBG-1: Biotechnology, Microscale Bioengineering Group, Forschungszentrum Jülich GmbH, Jülich, Germany

Dr. Stefan de Kok

Stefan de Kok obtained his PhD from Delft University of Technology by studying “metabolic engineering of free-energy (ATP) conserving reactions in Saccharomyces cerevisiae”. Afterwards, he moved to Amyris Inc. in California, where he worked on high-throughput, automated strain engineering technologies. Dr. De Kok led a project to optimize ligase cycling reaction (LCR) as a method for rapid and reliable assembly of up to 20 DNA parts into DNA constructs up to 20 kb. In addition, he was involved in metabolic engineering of yeast strains for farnesene production. Currently, Dr. de Kok works as scientist and project leader at Zymergen Inc. in California, where he utilizes robotic strain engineering technologies to develop microbes producing novel molecules, and to improve the performance of microbes used in industrial fermentation.

Dr. Jan Marienhagen

Institute of Bio- and Geosciences, IBG-1: Biotechnology, Synthetic Cell Factories Group, Forschungszentrum Jülich GmbH, Jülich, Germany

Prof. Henk Noorman

Henk Noorman was trained as Chemical Engineer from Groningen University (NL). He obtained a PhD in Bioprocess Technology from Delft University of Technology (NL, 1991), on microbal systems modeling. He became a post-doc fellow in a Nordic research consortium, and co-ordinated a fermentation scale-up project among academic groups in Sweden, Denmark and Norway. He then joined Gist-brocades and DSM in Delft (NL) and worked on fermentation development and implementation projects, mainly in the area of antibiotics and bio-based products. He also has been project manager for innovation projects, and received the DSM R&D Award 2010. Henk Noorman is currently working as Corporate Scientist Bioprocess Technology in the DSM Biotechnology Center and involved in numerous projects in Industrial Biotechnology, Food Specialties, Anti-Infectives, and the Corporate Research Program. In addition he is honorary professor at Technical University Delft working on Bioprocess Design and Integration. Teaching activities include courses in Delft, Wageningen (NL), Brac (Croatia) and Shanghai (China).

Prof. Matthias Reuss

Institut für Bioverfahrenstechnik, University Stuttgart, Germany

Cees Sagt

DSM Biotechnology Center, Delft, the Netherlands

Sean Simpson

Chief Scientific Officer, Lanzatech

Prof. Ralf Takors

Institut für Bioverfahrenstechnik, University of Stuttgart, Germany

Sander Tans

Kalvi Institute of NanoScience, Delft University of Technology

FOM-Institute for Atomic and MOlecular Physics (AMOLF), Amsterdam

Prof. Joost Teixeira de Mattos

Swammerdam Institute for Life Sciences, SILS, University of Amsterdam, the Netherlands.

Dr. Ruud Weusthuis

Associate Professor Microbial Biotechnology Bioprocess Engineering Wageningen University & Research

Prof. Gilles van Wezel

Molecular Biotechnology, Leiden University, the Netherlands

Rob Kerste

Brandweer & Biohazard Consultancy (B2C)


Currently there is a waiting list for the fellowships (PhDs). You can still register as fellowship/PhD but you will be placed on a waiting list. We will if participation is possible inform you a.s.a.p., but at least 3 weeks before the course. 

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