Advanced Course

Modelling and Computation for Micro-organisms in Bioprocesses

Course description

This course brings together contributions from different disciplines, i.e. bioprocess technology, applied physics, transport phenomena, molecular biology and biomedical sciences. They all address different elements on the coupling between several time and length scales in the simulation of different bioprocesses (e.g. bioreactor and bioprocess operation, microbial strain improvement, tissue and organ cultivation, plant design and integration). Computational methods will deepen the understanding of the connecting principles between different scales. The industrial relevance is underlined by the venue being the Biotech Campus Delft.

The idea of this course is to move from large-scale industrial bioprocesses (hectometers/days) down to the intracellular level (nanometers/microseconds), through several intermediate scales. These intermediate scales describe details inside the bioreactor (meters/hours) and in multicellular aggregates, as e.g. appearing in biofilms or tissues (millimeters/seconds). Top-down approaches allow answering particular questions in a natural way: a quantitative understanding at a higher level will – due to progressing insight or new requirements – be enhanced by details revealed by smaller scales approaches. A higher resolution description of the system will require a greater experimental effort to identify mechanisms and parameter values, together with considerably larger computational expenses. With the material presented in the course, the participants will better grasp the complexity of multileveled systems based on the underlying mechanisms. The increasing power of computational methods and hardware drastically reduces the need for simplification and thereby enhances the predictive capabilities of numerical models and our level of process understanding. This trend is expected to further develop at high pace in the coming years.

27 Novemer – 1 December 2023

Delft University of Technology, the Netherlands

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

Register
THE COURSE

Advanced Course Modelling and Computation for Micro-organisms in Bioprocesses

This intensive one-week course aims at active participation by those attending. A combination of theoretical (lectures) and practical (exercises, case study) work is offered. The course is build up around a few currently relevant biotechnological systems (e.g., lactic acid fermentations, antibiotic production, aerobic/anaerobic processes). Applications will be demonstrated with numerical models at all relevant scales, from factory and bioreactor to cell aggregate and intracellular processes, Particular emphasis will be on the identification of mechanisms and parameters, as well as on integration of scales to maximize complete system insight.

Lectures
The lectures are mainly scheduled in the mornings and late afternoons and will focus on the following themes:
• Industrial bioprocess design, integration and flowsheeting
• Gradients (concentration, shear rate, temperature) in bioreactors coupled to dynamic microbial response and compartmented kinetic models
• Industrial fermentation models with computational fluid dynamics and reaction dynamics by Euler-Lagrange approach and cell lifelines
• Micro-gradients in multicellular aggregates (biofilms, granules, tissues)
• Single-cell models including membrane transport, metabolic variation, intracellular dynamics and genetic diversity

Exercises and case study
The theory presented in lectures will be applied in exercises in the afternoon sessions. The participants will receive hands-on experience with state-of-the-art computational tools implemented in Ansys/Fluent, Comsol Multiphysics and MATLAB.

Who should attend?

The course is primarily aimed at academic and industrial specialists (MSc, PhD or equivalent experience) who seek broadening their knowledge and practical skills in multiscale modelling. Educational background in transport phenomena, basic reaction engineering and biotechnology is strongly advised. Affinity with biological systems is recommended.

Preparatory materials will be provided to help participants reaching the basic prerequisite knowledge for this course.

Course registration

Please register clicking the tab Register to attend the course. Applicants will be handled in order of the date of receipt. There is a maximum of participants for this course. We will inform you within two weeks if participation is possible.

PROGRAMME

Programme for 2023:

Monday, 27 November 2023
Theme: Process scale (homogeneous)
08.45 Welcome
09.00 Course introduction Henk Noorman
09.15 Black box model of microbes Sef Heijnen
10.30 Flow sheeting using black box models Adrie Straathof
11.45 Exercise: plant/full process simulation using SuperPro Designer Adrie Straathof
13:00 Lunch and Group picture
14:00 Exercise: plant/full process simulation using SuperPro Designer Adrie Straathof
17.00 Overview of modeling techniques in biotechnology Peter Verheijen
19.00 Social drink and buffet
Tuesday, 28 November 2023
Theme: Fermentor – industrial scale
09.00 Time and length scales in the fermentor Sef Heijnen
10.00 Characteristics of large scale bioreactors (gradients) Henk Noorman
11.00 Break
11.15 Genetic targeting via organism modelling Matthias Reuß
12.00 Exercise: Time & Length scales Cees Haringa
12.30 Flow and reaction modeling/computation Cees Haringa
13.00 Lunch
14.00 Flow and reaction modeling/computation Cees Haringa
14.45 Exercise: fermentor computation using Fluent Cees Haringa
17.00 Dynamic modeling of regulatory networks Matthias Reuß
Wednesday, 29 November 2023
Theme: Fermentor scale-down – lab scale
09.00 Building large scale model for Penicillium by model reduction Emrah Nikerel
10.15 Use of computational models to design scale-down simulators Cees Haringa
12.00 Exercise: CFD modelling Cees Haringa
13.00 Lunch + Labtour Food Innovation Center (optional)
14.00 Exercise: CFD modelling Cees Haringa
17.00 Scale-down in practice Ralf Takors
18.00 End of the day
Thursday, 30 November 2023
Theme: Aggregate scale
09.00 9-pool model Wenjun Tang
09.45 Models for cell aggregates Cristian Picioreanu
11.00 Continuation: Models for cell aggregates Cristian Picioreanu
12.00 Exercises: modelling gradients and microbial growth using COMSOL Multiphysics Cristian Picioreanu
13.00 Lunch
14.00 Exercises: modelling gradients and microbial growth using COMSOL Multiphysics Cristian Picioreanu
17.00 Observability of in vivo kinetic models Sef Heijnen
18.30 Course dinner
Friday, 1 December 2023
Theme: Single cell/molecule scale
09.00 Euler-Lagrange/Agent-based cell population modelling Cees Haringa
10.45 Cell cyclus modeling Mathhias Heinemann
12.00 Single Cell Modeling: The impact of cellular architecture on 4D spatial-temporal dynamics in cellular signal transduction processes Matthias Reuß
13.00 Lunch
14.00 Quantification of single cell performance and population heterogeneity (techniques + case studies) Frank Delvinge
15.00 Models, software, methods and outlook (plenary discussion) Henk Noorman
15.30 Directing cell population heterogeneity Frank Delvinge
16.30 Closing of the course Henk Noorman
17.30 Farewell drinks
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

Deadline for registration is 6 November 2023

The course fee is:

Early Bird €2.500,-*
Regular Fee €2.750,-
Small and medium-sized enterprises (SME/Startups/scaleups) €1.750,-**
Small and medium-sized enterprises (SME/Startups/scaleups) of Biotech Campus Delft €1.250,-**
PhD Students €1.250,-**

*To be eligible for the reduced early bird fee you need to register before 18 September 2023. If this date is exceeded, the regular fee applies.

**A limited number of fellowships is available for PhD students and SME’s (small/medium enterprise). Fellowships will be available on a first-come-first-serve basis. To apply as to one of these fellowships, please include a copy either of your registration as a PhD student from your university or a proof of the SME-status of the company you work at.

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 2 October 2023, 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.

BROCHURES
Brochure 2023
LECTURERS

Course board

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 Senior Science Fellow 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).

Cristian Picioreanu

Enviromental Science and Engineering,
King Abdullah University of Science and Engeering,
Thuwal, Kingdom of Saudi Arabia

Adrie Straathof

Bioprocess Engineering, Delft University of Technology,
Delft, the Netherlands

Cees Haringa

Bioprocess Engineering, Delft University of Technology
Delft, the Netherlands

Guest lecturers

Frank Delvigne

Gembloux Agro-Bio Tech, University of Liège,
Luik, Belgium

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 nearly 60 PhD students and is a member of the Royal Netherlands Academy of Arts and Sciences (KNAW). He is recipient of several science and education awards. 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, fermentation design and scale-up and scale down of industrial processes.
Prof. Heijnen teaches a wide variety of courses, and was elected at TU Delft’s 2003 ‘Leermeester’ (best lecturer).

Wenjun Tang

DSM BioTechnology Center Delft, the Netherlands
Mathematical Institute (MI), Leiden University, Leiden, the Netherlands
Centrum Wiskunde & Informatica (CWI),
Amsterdam, the Netherlands

Matthias Reuss

Stuttgart Center Sytems Biology, Stuttgart, Germany

Ralf Takors

Institut für Bioverfahrenstechnik, University of Stuttgart,
Germany

Peter J.T. Verheijen

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

Emrah Nikerel

Systems Biology and Bioinformatics Lab, Department of Genetics and Bioengineering, Yeditepe University,
Istanbul, Turkey

Matthias Heinemann

Molecular Systems Biology, University of Groningen, the Netherlands

REGISTER

Deadline for registration is 6 November 2023. Register for the course: Modelling and Computation for Micro-organisms in Bioprocesses

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    Testimonials

    Modelling and Computation 2022

    I am a molecular systems biologist focusing on biomedical applications but I was interested in learning more about the use of computational techniques in industry and biotechnology. This course was a fantastic way to explore the modelling approaches used for wide array of biotechnology applications as well as the underlying theory. I particularly appreciated the variety presented in the course, ranging in scale from industrial fermentors to individual metabolic pathways. For anyone interested in biotechnology from a computational perspective, or anyone interested in modelling in general, the course comes highly recommended. But do your homework – it’s a lot packed into one week and without proper preparation it will be difficult to keep up, especially if you aren’t already into industrial bioprocesses. Christoff Odendaal PhD student, University Medical Centre Groningen

    Modelling and Computation 2021

    Having attended the Bioprocess design course in 2017, I have had good experiences with the advanced courses provided by BioTech Delft / TU Delft. My expectation was that I would gain more knowledge on computational modelling applications surrounding bacterial fermentation like computational fluid dynamics (CFD) and how this is applied. These expectations were met and surpassed as I was positively surprised to find the course also delved into metabolic pathways and genetics. By taken the intracellular enzymatic reactions into account, in a holistic modelling approach, we learned each casus requires its own modelling approach.
    The course had a good balance between theoretical lectures and software practice, showing different software products available for CFD. The lecturers were all experienced experts in their relevant fields, stimulated discussion to improve understanding, and prepared their lectures around the main theme. Unfortunately, due to COVID restrictions I had to attend this course online, but the hybrid meeting was setup well although I would have liked to be able to attend the offline course diner.
    Given the intensity of the course, I would strongly recommend future participants to go through the preparatory material provided and to make sure the required software is installed up front. Although the emphasis of this course was on chemical engineering of microbial processes, I can strongly recommend this course to anyone working in the field of industrial process development as it will broaden your understanding of current technological possibilities and how these different fields interact.  

    Elco Backus
    Janssen vaccines and prevention, Senior associate scientist Process development

    Modelling and Computation 2021

    I am from a Chemical Engineering background with experience in CFD modeling during my PhD and started as a Postdoc at the Novo Nordisk Foundation Centre for Biosustainability for scale down studies of bioreactors. The extensive course was a perfect balance of modeling and experimental techniques, coupled with in depth understanding of the physics behind complex processes. The level of skills, expertise, and approachability of the presenters is something that made the course very relatable even to me coming from a different background in education. The exercises and case studies amalgamated a perfect blend of interaction and knowledge sharing between organizers and participants of the course, which added to the uniqueness. Overall, the value for time was entirely accounted for and I would strongly recommend this course to anyone especially looking for a modeling perspective in bioprocessing.  

    Soumendu Dasgupta
    Denmark Technical University, Postdoc at Novo Nordisk Foundation Centre for Biosustainability

    Multiscale Computational Methods in Bioprocesses 2018

    I have been out of science details for the last 8 years. The Advanced Course Multiscale Computational Methods in Bioprocesses brought me up to speed quickly with many aspects of the rapidly developing fields of modelling and computation. The course shows how different aspects in a biotechnology process can be described adequately and how to combine them to describe actual process limitations. One great aspect of the course is that you learn to build the models and do the simulation during the course. Another aspect is the nice overview given of the rapidly developing field of biotechnology and the new opportunities that this gives us. Joost Beekman Senior Scientist Integrated Processing, DSM Food Specialties

    Multiscale Computational Methods in Bioprocesses 2018

    I attended the course to get up to date with current status in modelling of fermentation based processes. My aim was to get a good enough understanding of the different software and model methods to be able to communicate and be a link between biochemists and engineers. I got a good start with this course. This is an intense course that requires knowledge about fermentation processes and reactor design. I must admit that it required a steep learning curve with 3 SW + plus other methods in just one week. The course is relevant on many levels for biochemical engineers working with CFDs and wants to get a broader knowledge, biochemical professions that wants an insight into the opportunities and possibilities of modelling used in CFD and chemical engineers that have recently begun working with fermentation. However, if you are like me and it is a while since you were active in the area, I advise you to refresh your skills in bio-kinetics and have a look at the software/CFD in advance. The course has a tight program with extremely knowledgeable speakers (high academic), practical modelling in different software, tours on the DSM Delft site, and the opportunities of interaction with the lectures and course participants. I believe that modelling is a good tool to support R&D and design and visualization of fermentation based processes. Susanne Gitlesen Special advisor, NORCE Norwegian Research Centre AS
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