Title : Structural Biology and Bioinformatics of the Two Partner Secretion Pathway  in Gram Negative Bacteria

by Vincent villeret 

Several important human, animal, and plant pathogens secrete adhesins and other virulence factors by means of the two-partner secretion (TPS) pathway. A TPS system is composed of two separate proteins, with TpsA the secreted protein and TpsB its associated specific outer membrane protein. We will present our structural and functional studies devoted to the secretion system of the Filamentous Hemagglutinin (FHA), the major adhesin of the whooping cough agent Bordetella pertussis, one of the most efficiently secreted proteins in Gram-negative bacteria. Structural biology and bioinformatic tools used to decipher the different aspects of the secretion process, from periplasmic transport of chaperones associated FHA, recognition and secretion by FhaC, the FHA associated outer-membrane protein , to folding and maturation outside the bacteria will be presented.  

- Title : Qualitative Methods for the Analysis of the Dynamics of Biological Networks

by  Eric Fanchon

The comprehension of cellular phenomena involves the construction and the analysis of molecular networks at work within the cells (interactions between genes, proteins and other molecules). The interactions are in general nonlinear and in addition these networks are often made up of many feedback loops. To this intrinsic complexity must be added the fact that current knowledge at the molecular level is incomplete. To go forward it is thus necessary to develop formalisms and tools which allow the analysis of these molecular interaction networks.
This course will be focused on a logical formalism decated to the qualitative analysis of the behaviour of interaction networks, originally developed by R. Thomas and collaborators. This formalism can be seen mathematically as a discrete abstraction of piecewise-linear differential systems. It allows to formulate general properties relating static features of the interaction networks to behavioural characteristics (like multistationarity and homeostasis). It allows also to perform simulations or inferences on specific, partially known, models.
The course will be illustrated by biological examples such as, for example, the genetic networks controlling the embryonic development of the fly, or the life cycle of the virus called lambda phage.  

Title : Petri Nets for the Qualitative Modelling of Biological Networks

 by Claudine Chaouiya
When facing a complex interaction network, the biologist needs new means to check the coherence of tentative models with the observed dynamics, to better understand the logics of the interactions and to simulate the system behaviour for various kinds of perturbations. In this respect, Petri Nets (PNs) and their extensions constitue a promising framework for the modelling, analysis and simulation of biological networks.
I will first briefly survey the various PN based models of biological networks found in the literature, classifying them according to the targeted biological application and the PN class (standard, coloured, stochastic, hybrid, etc.). Depending on the biological question to be addressed, one has to consider different abstraction levels: the molecular level (referring to biochemical networks), the genetic level (referring to genetic networks) or the tissue level (referring to inter-cellular networks). As quantitative information is rarely available, we are mainly interested in qualitative approaches.
I will focus on the qualitative modelling of metabolic pathways, and discuss to what extend a PN modelling can meet the different issues covered by the stoichiometric network analysis. Then, I will present our proposal of a PN framework for the logical modelling of gene regulatory networks, covering both coloured and standard Petri net representations.
These methodological aspects will be illustrated by the modelling of the regulation of the Tryptophan biosynthesis in E. Coli, which encompasses a mixed metabolic/genetic network. 

Title : Simulating Biological Systems in the Stochastic Pi-calculus

by  Andrew Phillips 
This course presents a programming language for designing and simulating computer models of biological systems. The language is based on a mathematical formalism known as the pi-calculus, and the simulation algorithm is based on standard kinetic theory of physical chemistry. The language will first be presented using a simple graphical notation, and will subsequently be used to model and simulate a number of intriguing biological systems. The main benefit of the language is its ability to model large systems incrementally, by composing simpler models of subsystems in an intuitive way. The language also facilitates mathematical reasoning of system models, which in future could help provide insight into some of the fundamental properties of biological systems.

Title: Structure-Based Rational Design of Drugs

by Rene Wintjens

Since several decades considerable effort has been devoted in industry and academia to rational design of novel molecules. Much has been done to develop new computational algorithms to aid in the design of molecules which fit on a protein target, typically an enzyme, to act as inhibitor or to perturb the activity of the protein target. Progress towards this goal demands a detailed structural characterisation of the protein target and identification of the ligand determinants essential for recognition. To this aim, X-ray crystallography has proved to be a highly valuable tool.