Advanced Course

Microbial Physiology and Fermentation Technology

Course description

This very successful course will be held in 2018 for the 30th 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.

15-26 January 2018

Delft University of Technology, the Netherlands

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

THE COURSE

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

Afternoon

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 Graduate School Biotechnological Sciences Delft Leiden, BSDL.

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.

PROGRAMME

Programme 2016:

Monday, 11 January 2016
Theme: Energy transduction and growth thermodynamics
08.45 Registration
09.00 Outline of the course Jack Pronk
09.30 Basic energetics of microbial metabolism Ton van Maris
10.30 Solute transport: mechanisms and energetics Jack Pronk
11.15 Balances Sef Heijnen
13.30 q-rates Sef Heijnen
14.00 Batch, fed-batch and continuous cultivation Ton van Maris
 15.00 Parallel sessions:
Exercises on energetics of microbial metabolism

Exercises on mass balances / q-rates

18.00 Welcome drink and buffet
Tuesday, 12 January 2016

Theme: Kinetics and stoichiometry of growth and product formation

09.00 Transport reactions and energy coupling: implications for industrial product formation Jack Pronk
10.15 Black box model: kinetics Sef Heijnen
11.30 Black box model: stoichiometry Sef Heijnen
13.45 Introduction to bioprocess design Sef Heijnen
14.30 Exercises on bioprocess design
Wednesday, 13 January 2016

Themes: Regulation of metabolism by environmental parameters and High-cell-density fermentation

09.00 Primary metabolism and its regulation Pascale Daran – Lapujade
10.00 Carbohydrate metabolism in yeasts: respiration versus alcoholic fermentation Jack Pronk
11.00 Physiological aspects of high cell density fermentation Jack Pronk
13.00 Fed-batch fermentation and transport phenomena Sef Heijnen
15.30 Microbial growth with mixtures of carbon substrates Jack Pronk
16.45 Optional: Visit tour research projects
Thursday, 14 January 2016

Theme: Metabolic networks: stoichiometry and fluxes

09.00 Metabolic network analysis Sef Heijnen
– Energy conversion pathways

– From product pathway reaction to network product reaction

– The network biomass reaction

11.45 Redox balances in microbial sugar metabolism: consequences for industrial product formation Ton van Maris
13.30 Bioenergetics of microbial growth and the cost of adaptation Joost Teixeira de Mattos
15.30 Fed-batch demo (1): design of the feed profiles
17.15 Fed-batch demo (2): measurements why and how
18.15 Buffet
Friday, 15 January 2016

Theme: Metabolic networks: stoichiometry and fluxes

09.00 Metabolic flux balancing: theory and applications Walter van Gulik
10.15 Computer exercises on metabolic network analysis
13.45 Metabolic studies in the Industrial contexts Ralf Takors
14.45 Exercises on high cell density fed-batch cultivation
17.30 Social drink
Monday, 18 January 2016

Theme: Rate based design

09.00 Rate based design of biosystems Sef Heijnen
10.00 Case study introduction, feedstock and stoichiometry variants, mass and energy balances Henk Noorman
10.30 Case study
14.00 Reactor types, rate limiting transport steps and reactor sizing Henk Noorman
14.30 Continuation with the case study
17.30 Large scale reactors: mixing and scale-up problems Henk Noorman
Tuesday, 19 January 2016

Theme: Regulation and control of metabolic fluxes

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 Through Van Leeuwenhoek’s eyes Lesley Robertson
11.30 Van Leeuwenhoek and Delft: a microbiological pilgrimage (social / cultural event) Lesley Robertson
14.30 Analysis of in vivo kinetics: rapid sampling and metabolite analysis Walter van Gulik
15.45 Fed-batch demo (3): practising fed batch calculations on the batch phase
Wednesday, 20 January 2016

Theme: Metabolic engineering

09.00 Metabolic engineering strategies for reducing costs Sef Heijnen
10.30 Design and engineering of industrial micro-organisms Christoph Wittmann
11.45 Engineering, fermentation and scale-up of fungi for protein production Rutger Douma
14.00 Evolutionary and reverse engineering Jack Pronk
15.15 Exercises on metabolic engineering strategies for reducing costs
17.00 Metabolic engineering of thermophiles Lee Lynd
Thursday, 21 January 2016

Theme: Heterogeneity and mixed cultures

09.00 Microbial community engineering for production of chemicals and bioenergy Robbert Kleerebezem
10.15 Spatio-temporal single-cell analysis in picoliter reactors Dietrich Kohlheyer
11.30 Responsive diversification – an explanation for lag phases? Matthias Heinemann
13.30 Fed-batch (4): calculations on mass balances of a fed-batch fermentation and evaluation
19.00 Course dinner, downtown Delft
Friday, 22 January 2016

Theme: Capita selecta

09.30 Low-pH fermentation to succinic acid, the basis for efficient recovery Mickel Jansen
10.45 High-throughput strain construction and phenotypic screening Stefan de Kok
13.45 Transcription factor-based biosensors for strain development Jan Marienhagen
14.45 Keynote Lecture Lee Lynd
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


FEE

The course fee is:

€ 3650 in case of payment received before 4 December 2017 or € 3900 in case of payment received on or after this date. In the event of cancellation before 4 December 2017, a full refund will be granted, after this date, a 25% fee charge will be made. To facilitate enrollment of young PhD-students from universities, a limited number of fellowships is available. The course fee with fellowship is € 1825. To apply, please include a copy of your registration as a PhD-student from your university.

The fee includes course materials, lunches, the buffets on Monday, 15th and Thursday, 18th and the course dinner on Thursday, 25st. 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.

Preparatory texts will be sent after receipt of the course fee. The complete set of course books 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

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. Ton van Maris

Ton van Maris joined the Faculty of Applied Sciences of the Delft University of Technology in 2005. Within the Industrial Microbiology section he leads a team of researchers on microbial physiology, thermodynamics-inspired metabolic engineering, engineering of transport and evolutionary engineering of industrial microorganisms, with a special focus on yeast. Besides many academic collaborations, Dr. van Maris has industrial collaborations with DSM and Amyris. Additionally, he is a member of the management team of BE-Basic. Dr. van Maris received his PhD degree (cum laude) in 2004 from the Delft University of Technology on Metabolic engineering of pyruvate metabolism in Saccharomyces cerevisiae. Next, he worked for Tate & Lyle at the 1,3-propanediol pilot plant and at the Astaxanthin factory.

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

Ing. Dirk Geerts, Ing. Yi Song

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

Guest lecturers

Dr. Rutger Douma

Rutger Douma (1981) finished the BSc and MSc Biotechnology program at Wageningen University, the Netherlands in 2005 with a specialization in process engineering and an internship at the Department of Chemical Engineering of UC Berkeley, USA. He became a PhD student in the bioprocess technology group of prof. dr. ir. J.J. Heijnen at Delft University of Technology, the Netherlands in 2006 and studied regulation, degeneration and transport aspects of penicillin biosynthesis in Penicillium chrysogenum. In 2010 Rutger started working as scientist for fermentation process development in Novozymes’ pilot plant in Bagsværd, Denmark. His work consists of optimization and scale-up of fermentation processes from R&D (liter scale) via pilot (m3 scale) to production scale (up to 160 m3). Rutger successfully introduced numerous production processes of a variety of products with a variety of production strains to different (international) factories and was promoted to senior scientist in 2014.

Prof. Matthias Heinemann

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

Dr. Mickel Jansen

Mickel Jansen did his MSc studies on Bio-process Engineering at the Wageningen University and Research (WUR), followed by a MSc study at the Delft University of Technology on Bio-chemical Engineering. Hereafter he did his PhD study at the Industrial Microbiology section of the Delft University of Technology on sugar metabolism in yeast. He received his degree in 2004, after which he moved to industry to become fermentation scientist at Corbion (then: Purac). There he mainly worked on the optimization of lactic acid manufacturing, including process development for some other products. In 2007 he moved to DSM, where he did projects on cephalosporin production optimization and application of novel feedstocks in fermentation processes and where he is now senior scientist. The last couple of years he is the lead scientist for the process development for succinic acid integrating metabolic engineering, strain selection, process development and optimization including scaling-up to industrial scale.

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.

Prof. Lee Lynd

Dartmouth College, Thayer School of Engineering, Hanover, USA

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

Prof. Ralf Takors

Institut für Bioverfahrenstechnik, University of Stuttgart, Germany

Prof. Joost Teixeira de Mattos

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

Prof. Christoff Wittmann

Universität des Saarlandes, Institut für Systembiotechnologie, Saarbrücken, Germany

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