The tutorial metabolism will be organized as a practical work with computers aiming at comparing various modeling approaches to study a metabolic network. To this purpose we will apply different tools to two metabolic networks, a very simple one to grasp the theoretical concepts and a network of medium complexity to apply the theoretical concepts and understand their interest. The program will be:

General presentationStoichiometry matrixof the network, Null-space, determination of the elementary flux modes (EFM), and analysis of metabolic networks with EFMs.Flux Balance Analysis(FBA) approach with different objective functions or/and constraints (FAME).Kinetic modellingof the network with simple rate equations and parameters from the literature. Description of the steady-states of the metabolic network. Role of metabolic and genetic regulations. Comparison with the EFM and the solution obtained with FBA. (Copasi, Berkeley Madonna, Python)Metabolic Control Analysis (MCA).Determination of control coefficients in different situations. Derive summation and connectivity equations (Control and Copasi).

The tutorial is completely hands-on. Students will use their laptop to apply different softwares based on different methods to study the same metabolic network and to compare the results. A booklet describing the metabolic network and the software used (which can be loaded before the thematic school) will be sent at the beginning of March. It will include a series of questions in order to practice with the proposed software and play with a metabolic network

**Target audience:** Biologists and physiologists interested in understanding
the role of metabolism, its rerouting in different normal or pathological
conditions (cancer, inborn errors of metabolism, Plant metabolism, metabolic
pathologies such as diabetes, obesity, aging, etc.), and as target of drugs.

**Prerequisite:** None although the notion of metabolic network and of rate equation
of reactions are supposed known.

**Equipment:** Students should bring their laptop. Internet connection is not needed,
but the sofwares should have been loaded (the list will be given at the beginning of
March)

**Enrollment limit:** 15 students maximum

**Duration:** 6 hours (2 sessions of 3 hours each).

**Tutors involved:**

Jean-Pierre Mazat (Université de Bordeaux and CNRS) http://jean-pierre.mazat.pagesperso-orange.fr Sabine Pérès (LRI Université Paris-Sud) https://www.lri.fr/~speres

**Relevant reviews**

1. Maarleveld TR, Khandelwal RA, Olivier BG, Teusink B, Bruggeman FJ. Basic concepts and principles of stoichiometric modeling of metabolic networks.Biotechnol J. 2013 Sep;8(9):997-1008. doi: 10.1002/biot.201200291.2. Llaneras F, Picó J. Stoichiometric modelling of cell metabolism.J Biosci Bioeng. 2008 Jan;105(1):1-11. doi: 10.1263/jbb.105.1. Review.3. Jeffrey D Orth, Ines Thiele & Bernhard Ø Palsson What is flux balance analysis?Nature Biotechnology volume 28: 245-2484. Schellenberger J, Que R, Fleming RM, Thiele I, Orth JD, Feist AM, Zielinski DC, Bordbar A, Lewis NE, Rahmanian S, Kang J, Hyduke DR, Palsson BØ Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox v2.0.Nat Protoc. 2011 Aug 4;6(9):1290-307. doi: 10.1038/nprot.2011.308.5. Reder, C., Metabolic control theory: a structural approach.J. Theor. Biol. 135 (1988) 175-201.6. Herbert Sauro, Systems Biology: Introduction to Pathway Modeling(2014)7. Edda Klipp, Wolfram Liebermeister, Christoph Wierling, Axel Kowald Systems Biology: A Textbook, 2nd Edition. ISBN: 978-3-527-33636-4