# Hosting labs of the CNRS

- The Interdisciplinary Research Institute (IRI), CNRS FRE 2963, Univ. Lille1 & Lille2, Lille/Villeneuve d'Ascq

**PI: Bernard VANDENBUNDER**

Ongoing scientific collaborations with MPI / Dortmund, MPI / Freiburg and MPI MiS / Leipzig

Short description of teams scientific interests:

The Interdisciplinary Research Institute is designed to foster under the same roof the interactions between biologists, computer scientists, mathematicians, physicists, chemists and engineers on topics related to the structure, the dynamics and the robustness of regulatory networks in the context of multifactorial diseases. Research is performed along five intertwined lines : chromatin dynamics and gene expression (Arndt Benecke and Pierre Olivier Angrand), differentiation and morphogenesis (Yasushi Saka), biophotonics (Laurent Héliot), nanobiotechnology (Rabah Boukherroub), and modelling (Ralf Blossey). The Institute combines its technological platforms of transcriptomics and biophotonics with the platforms of the surrounding institutes on proteomics (Lille Génopole), microfluidics and nanotechnologies (IEMN). - Laboratoire I3S, Team "BIOINFO", UMR 6070 CNRS/UNSA, Nice Sophia Antipolis

**PI: Gilles BERNOT**

Short description of teams scientific interests:

Biological systems are complex systems for which the modeling requires specific techniques of modularity, of determining of numerous parameters which are not directly measurable, and of model simplification or abstraction coherent with studied biological hypotheses, etc. We focus on the field of formal methods like temporal logic, constraints resolution or discrete state systems, which together lead to advances for biology. We then propose to model biological systems in a formal framework able to propose a set of potential experiments suitable to refute or validate biological hypotheses. Without this kind of formal approaches, we are obliged to make up a computational model of a biological system which reliably simulates known behaviors. The number of mandatory parameters is so huge that it is always possible to fit the parameters of a model to any new observed behavior. Model is thus not refutable. We then propose to model biological systems in a formal framework where refutation/validation of biological hypotheses are well defined. In particular we focus on the capabilities of a modeling framework to propose a set of potential experiments suitable to refute or validate at best biological hypotheses. - IRCCyN - UMR CNRS 6597, Team "MOVES", École Centrale de Nantes, Nantes

**PI: Olivier ROUX**

Short description of teams scientific interests:

A Timed Modelling Framework for Gene Regulatory Networks Analysis. René Thomas' discrete modelling of Gene Regulatory Networks (GRN) is a well known approach to study the dynamics resulting from a set of interacting genes. It deals with some parameters which reflect the possible targets of trajectories. Those parameters are a priori unknown, but they may generally be deduced from a well chosen set of biologically observed trajectories. Besides, it neglects the time delays for a gene to pass from one level of expression to another one. Our aim is to account for these time delays. For this purpose, we designed a more accurate abstraction of GRN where delays are now supposed to be non null unknown parameters. In the new designed modelling framework, we add clock variables (one clock for each gene) which measure times of increase or decrease, the dynamics of which are either -1, 0 or +1. Thus, the behaviour of the system is such that we stay in one location until a deadline is reached (i.e. the clock of one gene is equal to one of the linked delays). The final model is obtained when we put together all the locations according to the relevant relations of discrete transitions. Each discrete transition is compound of a guard (condition of firing), an action (which takes place when the transition is fired), and the new location to go. In each location, continuous transitions take place according to some dynamics such that dhx/dt is in {-1, 0, +1}. This makes up a hybrid automata. - Techniques de l’Ingénierie Médicale et de la Complexité (TIMC), Team "Formal methods for biological modeling", CNRS & Univ. Joseph Fourier, Grenoble

**PI: Eric FANCHON**

Ongoing scientific collaboration with MPI for Molecular Genetics, Berlin

Short description of teams scientific interests:

We are developing formal methods for the dynamical modeling of biological systems, represented as interaction networks. The global objective is to assist in reasoning during the process of model building and validation. This includes: building a model from observations; representing formally partial knowledge about global behaviour; inferring possible parameter values from known behaviours; revising an inconsistent model; generating proposals for new informative experiments. Our computational approach is based on constraints, currently Constraint Logic Programming (CLP) and boolean satisfiability (SAT). This allows to handle the set of models which satisfy some observational constraints, and is consequently a systematic approach. Through collaboration with biologists, we applied the method to gene regulatory networks in domains like cell-cell adhesion and nutritional stress in bacteria. We are now extending the methodology to signaling pathways (PI3K/Akt, apoptosis). - CNRS-UMR8550 and Ecole Normale Superieure, Team "Laboratoire de Physique Statistique", Paris

**PI: Vincent HAKIM**

Ongoing scientific collaboration with MPI MiS, Leipzig

Short description of teams scientific interests:

The team has a statistical physics/nonlinear dynamics background and does theoretical/computational/modeling work in neurophysiology (oscillations and dynamics in neural networks; synaptic plasticity and learning) and in genetics and development (dynamics of genetic networks, morphogenesis and evolution). The team has strong links with the ENS neurobiology lab and interactions with several biology labs in neighboring institutions (Institut Curie, ESPCI, Paris V). - Institute of Systems and Synthetic Biology, Team "SynthBio", Genopole®, Univ. Evry Val d'Essonne, CNRS UPS3201, Evry

**PI: Alfonso JARAMILLO**

Short description of teams scientific interests:

Our group works on the emerging discipline of Synthetic Biology, where we aim designing new biological systems with targeted behaviour. We are developing computational methods for de novo design of: proteins, transcriptional networks and metabolic pathways (retro-biosynthetic design). Our long-term goal is to establish a new methodology to re-design a living cell to produce useful chemicals after having performed a given computation. We experimentally synthetise and characterise all our designs. We are involved in projects such as biohydrogen production (http://biomodularh2.org) or microbial glucaric acid production. - DIMNP - UMR 5235 CNRS/UM1/UM2, Team "Biological Physics and Systems Biology", Montpellier

**PI: Ovidiu Radulescu**and**Andrea Parmeggiani**

Ongoing scientific collaboration with MPI for Molecular Genetics, Berlin

Short description of teams scientific interests:

Our team develops physical, mathematical and computer science approaches for the understanding of the functioning of biological systems. At the centre of our approaches is the multi-scale modelling of the biological processes by using statistical physics, dynamical systems and stochastic processes techniques. We collaborate with experimental teams in our lab (on systems biology of malaria, bacterial biofilms), in Montpellier (CBS, IGMM), and worldwide (USA, Brazil, Chile, India, Germany).