

Information on Black Board Teaching and Computer PracticalsPlease note that you will be able to visit one Blackboard Teaching Session (BB) or Computer Practical (CP) per day, which will take place on Thursday, Friday and Sunday afternoon from 16:45 to 18:45. Please chose one topic per day of the selection listed below. All in all you have 10 different topics to choose from. Please note, that all Computer Practicals and Blackboard Teachings will be held twice, except BB04 & BB05. Last update: 28.02.2018: BB6: Alberto MarinSanguino substituted for Michael Savageau Overview  Blackboard Teaching and Computer Practicals per day
Registration for the Blackboard Teaching and Computer PracticalsThe registration for the Blackboard and Computer Practicals can be found in the User Profile (login required). The number of places for these courses are limited and will be assigned on a first come, first served basis. For computer practicals, students are required to bring their own laptops with any required software preinstalled (preinstallation requirements listed at the end of each course). BB01 "Stochasticity"Frank BruggemannTBA BB02 Constraintbased modeling: from Flux Balance Analysis to resource allocation modelingBas Teusink (Amsterdam, NL)From a sequenced genome, the reconstruction of the metabolic network of an organism is the fastest path to increased understanding of its physiology (see ref [1] for a recent example). Such a reconstruction is an inventory of all metabolic reactions that an organism can potentially carry out – provided the bioinformatic inference of gene function was correct and the corresponding protein is expressed and active [2]. 1. Branco Dos Santos F, Olivier BG, Boele J, Smessaert V, De Rop P, Krumpochova P, et al. Probing the genomescale metabolic landscape of Bordetella pertussis, the causative agent of whooping cough. Appl. Environ. Microbiol. 2017; BB03 "Enzyme regulation, thermodynamics"Wolfram LiebermeisterTBA BB04 Modeling spatiotemporal processesFranziska Matthaeus (Frankfurt, DE)Biological components do not only interact, they are also subject to transport processes, such as diffusion or drift. Transport processes influence reaction kinetics and lead to spatiotemporal phenomena like traveling waves or the formation of spatial patterns. A common approach to model spatiotemporal processes are partial differential equations. We will derive, analyse and discuss classical descriptions of transport and reactiondiffusion equations. The course will cover diffusion, including properties of diffusion and the derivation of the diffusion equation, meaning and estimation of the diffusion coefficient, advection, anomalous diffusion, chemotaxis, and numerical approaches to solving the respective PDE’s. We furthermore consider reactiondiffusion systems and derive conditions for traveling waves and spatial patterns. The model system for traveling waves, the FisherKolmogorov equation, couples diffusion with logistic growth and exhibits solutions of fronts moving with constant profile and speed. In case of spatial patterning, we consider Turing systems, coupled reactiondiffusionequations, with distinct diffusion coefficients and specific nonlinear reaction terms. Apart from the mathematical background we will present many biological examples where these processes are of importance. BB05 Metabolic pathway design and analysisElad NoorIn this blackboard session, we will cover several aspects of pathway design in the context of metabolic engineering: BB06 A Novel Strategy to Accelerate the Modeling and Analysis of Complex Biological SystemsAlberto MarinSanguino (substituted for Michael Savageau)Although we have a welldefined concept of an organism’s genotype, its phenotypes – the biological functions implemented by its underlying biochemistry – are difficult to define and predict. We ultimately want to represent the phenotype by a mechanistic model that accurately describes the changes in the concentrations of the compounds under various conditions. The ‘architecture’ of a system can be inferred from highthroughput data, but numerous unknown kinetic parameters influence exactly how change in one concentration affects others. Often the phenotype becomes clear only when those parameters are known; even a simple model can exhibit many phenotypes given different parameter choices. Current approaches to determining phenotype thus focus first on finding parameter values for the underlying biochemistry, typically through a mixture of adhoc experimentation and computationally inefficient highdimensional numerical search. While these strategies have been used to fully characterize small systems in the pregenomic era, a mechanistic understanding of systems, even of moderate size, derived from genotype data remains elusive. We propose a fundamental shift towards a postgenomic computational paradigm in which we first analytically determine the space of possible phenotypes for a given network architecture and then predict parameter values for their realization, predictions that can guide experimentation and further numerical analysis. This ‘phenotypecentric’ paradigm combines four innovations with the potential to accelerate our understanding of complex biological systems: (1) a rigorous mathematical definition of biochemical phenotypes, (2) a method for enumerating the phenotypic repertoire based on the biomolecular network architecture, (3) an integrated suite of computational algorithms for the efficient prediction of parameter values and analysis of the phenotypic repertoire, and (4) a userfocused environment for navigating the resulting space of phenotypes and identifying biologically relevant features. These innovations will facilitate deterministic and stochastic simulations that require parameter values, will accelerate both hypothesis discrimination in systems biology and the design cycle in synthetic biology, and will enable investigators to achieve predictive understanding of biomolecular phenotypes from genotype. I will describe recent progress toward the realization of this potential and some of the remaining challenges. CP01 Advanced topics in parameter estimation with COPASIPedro Mendes (University of Connecticut, US) and Sven Sahle (University of Heidelberg, DE)COPASI is a widely used tool for creating, simulating and analysing kinetic models of biochemical reaction networks. In this session we will focus on parameter estimation/model fitting, which is one of the key features of COPASI and at the same time a crucial technique in computational systems biology. We will have practical demonstrations and exercises about setting up and running parameter estimation tasks with the software COPASI, including setups using data from multiple experiments under different conditions. We will discuss practical issues including the choice of optimisation algorithms (local/global optimisers). We will then cover how model fitting is used to answer qualitative and quantitative biological questions. (E.g. "Can my hypothesis explain the observed experimental data?“ and "Can I resolve the quantitative properties of biochemical processes from the given data?“). We will show how parameter identifiability can be analysed using COPASI. During the week of the course we will be available to answer questions on the features of COPASI that will not be covered in this session. Software: Please download and preinstall Copasi (latest stable version) for this practical. CP02 CellDesigner: A process diagram editor for generegulatory and biochemical networksAkira Funahashi (Keio, JP)CellDesigner is a software package for modeling and simulation of biochemical and gene regulatory networks, originally developed by the Systems Biology Institute in Japan. While CellDesigner itself is a sophisticated structured diagram editor, it enables users to directly integrate various tools, such as builtin SBML ODE Solver, COPASI, Simulation Core Libray and SBWpowered simulation/analysis modules. CellDesigner runs on various platforms such as Windows, MacOS X and Linux, and is freely available from our website at http://celldesigner.org/. In this course, I will explain how CellDesigner can be used from modeling perspectives. The first topic will feature network modeling using CellDesigner, and will show how she/he could build a model from scratch, and examine simulations. This topic also includes an explanation on how we build a biochemical network as a "map" which includes links to several existing databases, and how we build a mathematical model by the aspect of processdiagram based modeling. Once a model is described with appropriate mathematical equations and parameters, running a simulation on CellDesigner is quite straight forward. I will also explain how to easily tweak your model from CellDesigner's userinterface and observe some changes in the dynamics. Not just building a model from scratch, this course also introduces how we can "import" an existing model from several thirdparty databases (ex. BioModels.net, PANTHER database). This might be useful for users who actually read a paper and got interested in the model, but does not have enough experience on building a mathematical model by hand. This tutorial will cover both mathematical modeling and graphical modeling (create a model as a 'map') topics, and mainly focuses on mathematical modeling. Bringing your notebook PC with CellDesigner installed is highly recommended. Software: Please download and preinstall CellDesigner for this practical. CP03 VCell: compartmental and spatial modeling and simulation using reactions and reaction rulesMichael BlinovVirtual Cell (VCell, http://vcell.org) is an opensource platform (automatic installers for Windows, Mac OS and Linux) that provides powerful capabilities for kinetic modeling of cellular systems. It provides onestop simulation shopping: deterministic (compartmental ODE or reactiondiffusionadvection PDE), stochastic reactions (several SSA solvers), spatial stochastic (reactiondiffusion with Smoldyn), spatial hybrid deterministic/stochastic and compartmental networkfree agent based simulations. Software: Please download and preinstall Virtual Cell (Release version VCell 6.1) for this practical. CP04 Build better models by turning redundancy into actual modularity with Tellurium  a python modeling environmentTom Altenburg (Berlin, DE)This computer practical illustrates possible applications of Tellurium, which is a Python environment for building, solving and analyzing models in systems biology. The course will begin with a short introduction to i) antimony, which is Tellurium’s humanreadable modeling language and ii) roadrunner, Tellurium’s solver intended to simulate those models. From my point of view, Tellurium reflects an optimal mixture between simplicity and controllabilty for both the model and the workflow. Additionally, the modeling language antimony was specifically invented to be able to instanciate a model. A feature which supports building complex models in a modular manner. Software: Tellurium, Python and Jupyter must be installed on your laptop BEFORE the practical starts. Recommended is the usage Anaconda and Pip to install all three packages (works for Linux, Mac and Windows). If you are unfamiliar with those installation tools, please ask for help via mail: tom.altenburg@huberlin.de

