• Biotechnology Sciences Delft Leiden
Advanced Course

Metabolomics for Microbial Systems Biology – Brazil edition

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. We will teach this edition of the course in Brazil.

23-27 February 2015




Advanced Course Metabolomics for Microbial Systems Biology

Delft University of Technology, Universidade de São Paulo and Universidade de Campinas are pleased to announce the organization of an advanced course oriented to graduate students, young researchers and senior investigators, working in the area of microbial systems biology with interests in methods to determine intracellular metabolite concentrations and fluxes. The course is based on (method) lectures, computer exercises and conference talks showing results from different research groups in Brazil, Netherlands, Germany and United States of America. The official course language is English.

The first two days are mainly dedicated to experimental techniques, including cultivation approaches for steady-state analysis and stimulus response experiments. Proper sampling and sample handling procedures for reliable and reproducible metabolome analysis will be discussed and validation calculations (computer exercise) are performed. The main measurement techniques addressed are based on liquid and gas chromatographic separation, coupled to mass spectrometry. The third and fourth days will be focused 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 identify intracellular cycles under stationary state as well as dynamic conditions. The last day will show-case some metabolomics research highlights from Brazil, the Netherlands and USA.


  • 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


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. In every practice, at least two instructors will be present to help in the solution of eventual problems.

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 graduate students and postgraduates (MSc, 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. It is our intention to conform a select group of attendants of no more than 36 participants. Our aim is to have a multi-disciplinary group, with people from the industry and the academy.


Programme 2015

Monday, 23 February 2015

Theme: Rapid sampling, identification and quantification of metabolites

09.15 Outline of the course and introduction of participants Gregorio Gomez and Aljoscha Wahl
09.45 Introduction to microbial metabolomics Walter van Gulik
10.45 Rapid sampling for quantitative metabolomics Walter van Gulik
13.30 Mini-review MS technologies Reza Seifar
14.15 Identification of metabolites Massuo Jorge Kato
15.30 Quantitative analysis of intracellular metabolites using LC-MS/MS Reza Seifar
16.15 NMR-based metabolomics Jan Schripsema
Tuesday, 24 February 2015

Theme: Validation of sampling & quantification protocols & Perturbation and validation strategies

09.00 Development of quantitative analysis of metabolites using GC isotope dilution mass spectrometry Reza Seifar
09.45 Exercises: calculating concentrations from ID-MS data and validation of sampling and extraction protocols
13.45 Perturbation strategies for estimation of in-vivo kinetic properties of enzymes Walter van Gulik
14.30 Validation of metabolite quenching and extraction Walter van Gulik
15.30 Tackling cellular compartmentalization: application of sensor reactions Walter van Gulik
16.15 Thermodynamic validation of metabolite data Aljoscha Wahl
Wednesday, 25 February 2015
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 Andreas Gombert
12:00 Computer exercises on metabolic flux analysis
17:00 Steady state flux analysis using 13C labeling at isotopic steady state Katharina Nöh
Thursday, 26 February 2015
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 models
15:30 Analysis of dynamic systems Tim Gardener
16.30 Model analysis and visualisation techniques & demonstration Katharina Nöh
Friday, 27 February 2015
Theme: Outlook and future developments
09.00 Lost in transition – dynamics in the start-up of glycolysis Aljoscha Wahl
10.45 13C Metabolic flux analysis in tubercolosis Katharina Nöh
13.30 Flux analysis in PHA production Gregorio Gomez
14.45 Changing the cofactor specificity of a dehydrogenase in E.coli Karel Olavarria
15.45 Evaluation of the course

Course board and lecturers

Dr. Tim Gardner
Founder/CEO at Riffyn (previously Vice President, R&D Programs at Amyris)

Prof. Andreas K. Gombert
University of Campinas, Faculty of food technology, São Paulo, Brazil

Prof. Gregório Gomez
University of Sao Paulo, Department of microbiology, São Paulo, Brazil

Dr. Walter van Gulik
Cell Systems Engineering, Department of Biotechnology, Delft University of Technology, the Netherlands

Prof. Massuo Jorge Kato
University of Sao Paulo, Institute of chemistry, São Paulo, Brazil

Dr. Katharina Nὅh
Modeling and Simulation Group, Research Centre Jülich, Germany

Dr. Karel Olavarria
University of São Paulo, Department of microbiology, São Paulo, Brazil

Dr. Reza Maleki Seifar
Cell Systems Engineering, Department of Biotechnology, Delft University of Technology, the Netherlands

Prof. Jan Schripsema
Universidade Estadual do Norte Fluminense, Campos dos Goytacazes, Brazil

Dr. Aljoscha Wahl
Cell Systems Engineering, Department of Biotechnology, Delft University of Technology, the Netherlands


This Advanced Course was originally developed by BSDL. For this Brazil edition, several partners teamed up:

BSDL logo BE Basic logo USP logo Unicamp logo TU Delft logo

BE-Basic foundation

The BE-Basic Foundation (Biotechnology based Ecologically Balanced Sustainable Industrial Consortium) is an international public-private partnership that develops industrial biobased solutions to build a sustainable society. The BE-Basic Program was founded early 2010 and originally coordinated by Delft University of Technology. This course is part of the educational programme of BE-Basic.


Unicamp is a public university in the State of São Paulo, Brazil.  The university has approximately 17000 undergraduate and 20000 graduate students. Unicamp has three campuses – in Campinas, Piracicaba and Limeira – which are home to 22 teaching and research centers. It also has a vast hospital complex (two large hospitals in Campinas, and one in each of the neighboring towns of Sumaré and Hortolândia); 23 interdisciplinary centers; two technical high schools; and a series of support units within a universe of about 50 thousand people in which thousands of research projects are carried out.

University of São Paulo

The University of São Paulo (USP) is a public university in the State of São Paulo, Brazil. It is the largest Brazilian university with approximately 90,000 enrolled students and eleven campuses. USP has undergraduate and graduate programs in all fields of knowledge.

Delft University of Technology

Delft University of Technology, also known as TU Delft, is the largest and oldest Dutch public technical university, located in Delft, Netherlands. With eight faculties and numerous research institutes it hosts over 19,000 students (undergraduate and postgraduate) and more than 3,300 scientists.


Course location

The course will be held at the Department of Food Engineering (FEA) at Unicamp, Campinas, Brazil.
To registered participants, we will later on send more detailed info on class rooms.

Course fee

The course will be offered as a regular course in the university program. Therefore, no course fee is charged.


Due to the overwhelming interest in this course, we had to close registration already. Please let us know by email if you would like to stay informed about future metabolomics courses (anywhere).