Advanced Course

Metabolomics for Microbial Systems Biology

Course description

The advanced course Metabolomics for Microbial Systems Biology aims at teaching state of the art methods of quantitative metabolomics to industrial and academic research professionals (i.e. MSc, PhD). The focus is to gain insights into the complex metabolic control of central carbon metabolism and connected product formation pathways in industrial micro-organisms. The course covers recent developments in rapid sampling methods, measurement techniques and modeling approaches for microbial systems. This course was held for the 5th time in 2016.

planned for June 2020

Delft University of Technology, the Netherlands

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


Advanced Course Metabolomics for Microbial Systems Biology

This intensive, activating, one-week course aims at providing fundamental and applied knowledge in the field. To this end, the course is set up as an alternating program of expert lectures and exercises. A laptop and calculator is required. The official course language is English.

The first two days are mainly dedicated to experimental techniques, from steady-state analysis to stimulus response experiments. Proper sampling and sample handling procedures for reliable and reproducible metabolome analysis will be discussed and exercise calculations are performed. The main measurement techniques addressed are based on liquid and gas chromatographic separation, coupled to mass spectrometry.

The third and fourth day focus on theoretical and modeling aspects of Systems Biology. Approaches from network reconstruction, stoichiometric and thermodynamic network analysis and in-vivo kinetic modeling will be covered. 13C tracer methods will be discussed to extend the information content of stationary state as well as dynamic experiments.

The last day will be dedicated to future developments and advanced applications of quantitative metabolomics to tackle specific biological questions, whereby also other hierarchical levels of the cell will be taken into account.


Attention will be on a variety of themes:

  • Rapid sampling and quantitative analysis
  • Metabolite quantification and validation using
  • Isotope Dilution Mass Spectrometry, IDMS
  • Perturbation strategies
  • Estimation of extra- and intracellular rates from experimental data
  • Kinetic modeling and approaches to handle parameter identification problems
  • Outlook and future developments


Several exercises will be performed to familiarize the participants with the theory and practice and to illustrate the utility and utilization of quantitative metabolomics in modern biotechnology. IDMS calculations will be carried out using Microsoft Excel. Flux analysis and dynamic simulations are performed using the numerical computing environment MATLAB. Prior knowledge of MATLAB is advantageous – a tutorial for learning the required (basic) MATLAB knowledge will be sent prior to the course.

Study load

The course (including preparatory materials) is valued 41 hours of work.

Who should attend?

This Advanced Course is aimed at participants from industry, universities and research institutions who want to update and extend their theoretical knowledge and practical insight in quantitative metabolomics and modeling. The course is intended for postgraduates (MSc, PDEng, PhD), with a sound background in microbiology, microbial physiology, biotechnology, biochemistry or biochemical engineering, with a basic working knowledge in some of the other disciplines and an affinity to applied mathematics. 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. Deadline for application is 4 June 2018. Applicants will be handled in order of the date of receipt.


Programme 2018

Monday 18 June 2018
Theme: Rapid sampling and quantitative analytics
08:30 Registration
09:00 Short introduction on Surfaces and BioTech Delft
09:15 Outline of the course and introduction of participants
Walter van Gulik
09:45 Introduction to microbial metabolomics
Walter van Gulik
10:45 Rapid sampling for quantitative metabolomics
Walter van Gulik
12.30 Lunch
13:30 MS-technologies
Martin Pabst
14:15 Identification of compounds using high-mass- resolution GC-TOF-MS
Marco Oldiges
15:15 Understanding penicillin G production pathway using stimulus response strategy and targeted metabolite analysis by LC-MS/MS
Marco Oldiges
16:00 Understanding penicillin G production pathway using stimulus response strategy and targeted metabolite analysis by LC-MS/MS
Martin Pabst and Amit Deshmukh
16:45 NMR for metabolomics
Martin Pabst
17:30 Social drink and buffet

Tuesday 19 June 2018
Theme: Quantification and validation using isotope dilution mass spectrometry and perturbation and validation strategies
09:00 Development of quantitative analysis of metabolites using GC isotope dilution mass spectrometry
Aljoscha Wahl
10:00 Exercises: calculating concentrations from ID-MS data and validation of sampling and extraction protocols
Walter van Gulik and Martin Pabst
12.15 Lunch
13:45 Perturbation strategies for estimation of in-vivo kinetic properties of enzymes
Walter van Gulik
14:30 Thermodynamic validation of metabolite data
Aljoscha Wahl
15:30 Tackling cellular compartmentalization: application of sensor reactions
Walter van Gulik
16:15 Futile cycles during Penicillin production: mimic large scale on the bench using a feast/famine regime
Aljoscha Wahl
17:15 Introduction Matlab (optional)
Aljoscha Wahl
18:00 End of the day

Wednesday 20 June 2018
Theme: Estimation of extra- and intracellular rates from experimental data
09:00 Calculation of net conversion rates from reactor mass balances
Walter van Gulik
09:45 Analysis, validation and estimation of rates
Walter van Gulik
10:45 Introduction to metabolic flux analysis
Aljoscha Wahl
11:30 Computer exercises on metabolic flux analysis
Aljoscha Wahl
12.45 Lunch
13:30 Continuation
15:45 Steady state flux analysis using 13C labeling at isotopic steady state
Katharina Nöh
17:00 Computer demonstration/exercises on 13C isotopomer modeling
Aljoscha Wahl and Katharina Nöh
18:00 End of the day

Thursday 21 June 2018
Theme: Kinetic modeling, parameter identification and visualization approaches
09:00 Steady state flux analysis using 13C labeling at isotopic transient states
Katharina Nöh
10:00 Setting up a kinetic model using mechanistic enzyme kinetics
Aljoscha Wahl
11:00 Computer exercise: kinetic ODE models
Aljoscha Wahl
12.45 Lunch
13:30 Continuation
14:30 Hybrid systems modelling approach for efficient dynamic flux estimation
Aljoscha Wahl
15:30 Model analysis and visualisation techniques
Katharina Nöh
16:15 Computer demonstration on model analysis and visualisation
Peter Droste
18:00 Canal Tour by Boat
19:00 Course Dinner

Friday 22 June 2018
Theme: Outlook and future developments
09:30 Analytics in industry
Denise Jacobs
10:45 Regulation of metabolism: navigating between desired and fatal states
Bas Teusink
11.45 Lunch
13:30 How E. coli integrates growth rate regulation with amino acid and fatty acid anabolism
Greg Bokinsky
14:45 Imaging metabolites and metabolic pathways in cancer tissues
Liam McDonnell
15:45 Evaluation and 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 28 May 2020

The course fee is:

Early Bird €2.500,-*
Regular Fee €2.750,-
PhD Students €1.250,-**

*To be eligible for the reduced early bird fee you need to register before 9th of April 2020. 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 23 April 2020, 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

Dr. Walter van Gulik

Cell Systems Engineering, Department of Biotechnology, Delft University of Technology, 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).

Guest lecturers

Dr. Greg Bokinsky

Delft University of Technology, Department of Bionanoscience, Delft, the Netherlands

Prof. Alejandro Cifuentes

National Research Council of Spain (CSIC), Laboratory of Foodomics, CIAL, Madrid, Spain

Dr. Amit T. Deshmukh

Amit studied Chemical Engineering from 1996 to 2000 at the University of Pune, India. In 2005, he traveled to Germany to pursue MSc. in Chemical Engineering with specialization in Bio-chemical engineering at Technische Universität Dortmund. From 2008-2012, he did his PhD in the group of Prof. J.J. (Sef) Heijnen at the Delft University of Technology, Delft. During his PhD, he worked on elucidating in-vivo enzyme kinetics in P.chrysogenum. For last four years, he working as a lead scientist at DSM Biotechnology Center, Delft, carrying out R&D activities for industrial scale fermentation. His work involves scale up/down of fermentation processes, specifically for production of penicillin and cephalosporin antibiotics. He is also part of teaching activities that include courses in Delft (NL) and Shanghai (China).”

Dr. Peter Droste

Peter Droste studied computer science with focus on media science, computer graphics and visualization at the University of Siegen, Germany, and finished his M.C.S. in 2006. Thereafter, he continued by making his doctoral degree which he succeeded in 2011 with Magna Cum Laude. Since 2009, he was visiting researcher and from 2011 to 2013 research assistant at the institute IBG-1: Biotechnology, Forschungszentrum Jülich. In May 2013, he founded Omix Visualization GmbH & Co. KG to continue his successful scientific work in the private commercial sector.

Dr. Liam McDonnell

Leiden University Medical Center, Leiden, the Netherlands

Dr. Katharina Nὅh

Modeling and Simulation Group, Research Centre Jülich, Germany

Dr. Martin Pabst

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

Prof. Marco Oldiges

Bioprocesses and Bioanalytics Group, Research Centre Jülich, Germany

Prof. Bas Teusink

Vrije Universiteit Amsterdam, the Netherlands


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