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.

11 – 15 June 2018

Delft University of Technology, the Netherlands

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

THE COURSE

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.

Lectures

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

Exercises

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.

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.

PROGRAMME

Programme 2016

Monday, 11 July 2016
Theme: Rapid sampling and quantitative analytics
09.00 Registration
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
13.30 Quantitative analysis of intracellular metabolites using LC-MS/MS Reza Seifar
14.15 Identification of compounds using high-mass-resolution GC-TOF-MS Marco Oldiges
15.15 LC-MS/MS for the quantitative analysis of product pathway intermediates Marco Oldiges
16.00 Application of LC-MS/MS for Penicillin biosynthesis pathway intermediates Reza Seifar and Amit Deshmukh
16.45 NMR for metabolomics Peter Lankhorst
17.30 Social drink and buffet
Tuesday, 12 July 2016
Theme: Quantification and validation using isotope dilution mass spectrometry
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 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 Octave introduction / tour
Wednesday, 13 July 2016
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 Walter van Gulik
11.30 Computer exercises on metabolic flux analysis
15.45 Steady state flux analysis using 13C labeling at isotopic steady state Katharina Nöh
17.00 Computer demonstration/exercises on 13C isotopomer modeling
Thursday, 14 July 2016
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
14.30 Hybrid systems for efficient parameter estimation Aljoscha Wahl
15.30 Model analysis and visualisation techniques Katharina Nöh
16.15 Computer demonstration on model analysis and visualisation Peter Droste
19.00 Course dinner, Downtown Delft
Friday, 15 July 2016
Theme: Outlook and future developments
09.00 Regulation of metabolism: navigating between desired and fatal states Bas Teusink
10.45 Foodomics Alejandro Cifuentes
13.30 How E. coli integrates growth rate regulation with amino acid and fatty acid anabolism Greg Bokinsky
14.45 Closing lecture: Imaging metabolites and metabolic pathways in cancer tissues Liam McDonnell
15.45 Evaluation of the course
16.00 Farewell drink
LOCATION

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
E BiotechDelft@tudelft.nl
W http://www.biotechnologycourses.nl


FEE

The course fee is:

Early bird fee: € 2500 when payment is received before 30 April 2018, or
Regular fee: € 2750.- in case payment is received on or after this date.

In the event of cancellation before 30 April 2018, a full refund will be granted, after this date, a 25% fee charge will be made. To facilitate enrolment of PhD-students, a number of fellowships is available. The course fee with fellowship is € 1250.-. To apply, please include a copy of your registration as a PhD-student at your university.

The fee includes course materials, lunches, the buffet on Monday and the course dinner on Thursday. The fee does not cover other meals and lodging.

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.

Hotel accommodation can be arranged at your request directly at biotechdelft@tudelft.nl.

Preparatory texts will be sent after receipt of the course fee. The complete course book will be supplied at the start of the course.

Course fees can be paid by bank transfer or credit card (we are required to charge extra costs for this option; please contact us). TU Delft employees can use their internal (project) code. Customers are requested to pay the course fee within 30 days after the invoice date, but at the latest six weeks before the course starts. In case of payment before this date, the reduced course fee applies. After this date, we charge the full course fee. The course fees need to be on our bank account before the course starts.

DOWNLOADS
LECTURERS

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).

Dr. Reza Maleki Seifar

Reza Maleki Seifar Scientist and Head of the Analytical Group in Cell systems biology. He was trained as an analytical chemist at Tehran University (Iran). After finishing his PhD in analytical chemistry at University of Amsterdam (the Netherlands) in 1998, he had postdoc positions at the Free university of Amsterdam and the University of Groningen (also in the Netherlands). After working as a scientist at A*STAR (Singapore), he joined the Department of Biotechnology of Delft University of Technology in 2005. His main research interests are (1) quantitative analysis of targeted metabolites in different microbial systems, (2) understanding the molecular interactions and stability of metabolites during and after sample preparation, and (3) development of new analytical methods to improve accuracy and reproducibility of data.

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. Peter Lankhorst

DSM, Delft, the Netherlands

Dr. Liam McDonnell

Leiden University Medical Center, Leiden, the Netherlands

Dr. Katharina Nὅh

Modeling and Simulation Group, Research Centre Jülich, Germany

Prof. Marco Oldiges

Bioprocesses and Bioanalytics Group, Research Centre Jülich, Germany

Prof. Bas Teusink

Vrije Universiteit Amsterdam, the Netherlands

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