Systems Biology
Group leader: Vincent Fromion
Systems biology is a field of research that highlights the dynamical interactions between different parts of a biological system as well as between biological systems and their environment.
In this general context, the BioSys team aims at developing mathematical and algorithmic methods to model, analyze, and simulate complex biological systems, ranging from the scale of intracellular processes to the scale of an organism (or a community of organisms) within its environment. Using an integrative approach, the team also provides computational tools to represent and manage large and heterogeneous datasets, coming for instance from `omic’ data, high-throughput phenotyping or microscopic imaging.
Our main areas of expertise are in Applied Mathematics: dynamical systems (deterministic or stochastic), control theory, optimization (convex or non-convex) and in Engineering Sciences: automatic control, image processing and scientific computing. On a biological level, our research mainly concern model organisms such as the Gram-positive bacterium Bacillus subtilis and the plant Arabidopsis thaliana. Generally, research questions centered on concrete biological systems are approached in tight collaboration with biology teams inside and outside INRA.
Research themes
Located at the interface between different fields, the team combines applied research, with direct biological applications, with the development of methodological tools. Our research can be categorized into four axes, each one illustrated below by some representative publications.
Analysing and modelling biological regulatory networks
Goelzer A, Bekkal Brikci F, Martin-Verstraete I, Noirot P, Bessières P, Aymerich S and Fromion V. Reconstruction and analysis of the genetic and metabolic regulatory networks of the central metabolism of Bacillus subtilis. BMC Syst Biol, 2(1):20, 2008. [http]
Calzone L, Tournier L, Fourquet S, Thieffry D, Zhivotovsky B, Barillot E, Zinovyev A. Mathematical modelling of cell-fate decision in response to death receptor engagement. PLoS Comput Biol, 6(3):e1000702, 2010. [http]
Lubitz T, Schulz M, Klipp E, Liebermeister W. Parameter balancing in kinetic models of cell metabolism. Journal of Physical Chemistry B 114(49):16298-16303, 2010. [http]
From systemic cell models to a systemic representation of multicellular organisms
Goelzer A, Muntel J, Chubukov V, Jules M, Prestel E, Nölker R, Mariadassou M, Aymerich S, Hecker M, Noirot P, Becher D and Fromion V. Quantitative prediction of genome-wide resource allocation in bacteria. Metab Eng, 32:232–243, 2015. [http]
Borkowski O, Goelzer A, Schaffer M, Calabre M, Mäder U, Aymerich S, Jules M and Fromion V. Translation elicits a growth rate-dependent, genome-wide, differential protein production in Bacillus subtilis. Mol Syst Biol, 12(5):870, 2016. [http]
Noor E, Flamholz A, Bar-Even A, Davidi D, Milo R, Liebermeister W. The protein cost of metabolic fluxes: prediction from enzymatic rate laws and cost minimization PLoS Computational Biology, 12 (10):e1005167, 2016. [http]
Goelzer A and Fromion V. Resource allocation in living organisms. Biochem Soc Trans, BST20160436, 2017. [http]
Bulović A, Fischer S, Dinh M, Golib F, Liebermeister W, Poirier C, Tournier L, Klipp E, Fromion V, Goelzer A. Automated generation of bacterial resource allocation models. Metabolic Engineering, 55:12-22, 2019. [http]
Analysis of spatio-temporal processes within living cells
Domínguez-Escobar J, Chastanet A, Crevenna AH, Fromion V, Wedlich-Söldner R, Carballido-López R. Processive movement of MreB-associated cell wall biosynthetic complexes in bacteria. Science, 333(6039):225, 2011. [http]
Miquel M, Trigui G, d'Andréa S, Kelemen Z, Baud S, Berger A, Deruyffelaere C, Trubuil A, Lepiniec L, Dubreucq B. Specialization of oleosins in oil body dynamics during seed development in Arabidopsis seeds. Plant Physiol, 164(4):1866, 2014. [http]
Billaudeau C, Chastanet A, Yao Z, Cornilleau C, Mirouze N, Fromion V, Carballido-López R. Contrasting mechanisms of growth in two model rod-shaped bacteria. Nature Communications, 8, 2017. [http]
Deslandes F, Thiam A, Forêt L. Lipid droplets can spontaneously bud off from a symmetric bilayer. Biophysical Journal, 113(1), 15-18, 2017. [http]
Methods development for systems biology
Goelzer A, Fromion V and Scorletti G. Cell design in bacteria as a convex optimization problem. Automatica, 47(6):1210, 2011. [http]
Tournier L and Chaves M. Interconnection of asynchronous Boolean networks, asymptotic and transient dynamics. Automatica, 49(4):884, 2013. [http]
Fromion V, Leoncini E, Robert P. A stochastic model of the production of multiple proteins in cells. SIAM J Appl Math, 75(6):2562, 2015. [http]
Bergou EH, Gratton S, Vicente LN. Levenberg-Marquardt methods based on probabilistic gradient models and inexact subproblem solution, with application to data assimilation. SIAM/ASA J Uncertainty Quantification, 4(1):924, 2016. [http]
Deslandes F, Laroche B, Trubuil A. Fusion detection in time-lapse microscopy images: application to lipid droplets coalescence in plant seeds. IFAC-PapersOnLine, 49(26), 239-244, 2016. [http]
Research projects
Ongoing projects (selection)
DALLISH [2017-2020] Data Assimilation and Lattice LIght SHeet imaging for endocytosis / exocytosis pathway modeling in the whole cell (funded by ANR)
Consortium:
- INRA-MaIAGE (Teams DynEnVie et BioSys)
- Inria (Team-projects Serpico / Fluminance / Beagle)
- Institut Curie (U1143 / UMR144)
ICycle [2017-2020] Interconnection and feedback control of two cyclic modules in mammalian cells (funded by ANR)
Consortium:
- INRA-MaIAGE (Team BioSys)
- Inria (Team-project BIOCORE)
- IBV, Institut de Biologie de Valrose (Team Circadian System Biology)
Past projects (selection)
BaSysBio [2006-2010] Bacillus Systems Biology (European project FP6)
Basynthec [2010-2014] Bacterial Synthetic minimal genomes for biotechnology (European project FP7)
IMSV [2012-2016] Institut de Modélisation des Systèmes du Vivant (Lidex project within Paris-Saclay University)
List_MAPS [2015-2019] Training and research in Listeria monocytogenes Adaptation through Proteomic and Transcriptome deep Sequencing Analysis (European ITN Project, Initiative Traning Network)
ProteinFactory [2015-2018] Engineering of new-generation protein secretion systems (European ITN Project, Initiative Traning Network)
Softwares & Ontologies
BiPON: an ontology permitting a multi-scale systemic representation of bacterial cellular processes and the coupling to their mathematical models. This work has been funded by the project IMSV.
BiPOm: an ontology permitting a multi-scale systemic representation of metabolic processes. This work has been funded by the project IMSV.
BiPSim: a flexible and generic stochastic simulator of bacterial cellular processes. This work has been funded by the project IMSV.
BasyLiCA: a user-friendly open-source interface and database dedicated to the automatic storage and standardized treatment of Live Cell Array data. This work has been funded by the project BaSysBio.
Parameter balancing: Online tool and software code for parameterising kinetic metabolic models.
RBApy: Python package for creating, calibrating and simulating RBA models for bacteria.
SBtab: Software support, including SBML model converter, for the structured table format SBtab.
Team members
Permanent members
El Houcine Bergou, Researcher.
Marc Dinh, Engineer.
Vincent Fromion, Research director, group leader.
Anne Goelzer, Research engineer.
Wolfram Liebermeister, Research director.
Laurent Tournier, Researcher.
Alain Trubuil, Research engineer.
PhD students, post-doctoral fellows and associated researchers
Claudia Lopez-Zazueta, Post-doctoral fellow.
Oliver Bodeit, PhD student.
Ana Bulović, PhD student.
Ousmane Diop, PhD student.
Léon Faure, PhD student.
Olivier Inizan, PhD student.
Yunjiao Lu, PhD student.
Jana Zaherddine, PhD student.
Sabine Peres, Associate professor LRI, IUT d'Orsay.
Former members
Cécile Moulin, PhD student 2016-2020.
Pierre Hodara, Post-doctoral fellow. 2018-2020.
Marwa Zaarour, PhD student 2015-2019.
Guillaume Jeanne, PhD student 2015-2018.
Claire Baudier, PhD student 2014-2018.
Stéphan Fischer, Post-doctoral fellow 2015-2017.
Vincent Henry, Post-doctoral fellow 2015-2017.
François Deslandes, PhD student 2014-2017.
Renaud Dessalles, PhD student 2013-2017.
Elise Laruelle, PhD student 2013-2017.
Aida Kalantari, PhD student 2013-2016.
Ghislain Fievet, Engineer 2015-2016.
Joel Yao, Post-doctoral fellow 2014.
Houda Bouraoui, Post-doctoral fellow 2014.
Emanuele Leoncini, PhD student 2011-2013.
Marouane Ait El Faqir, PhD student 2012-2015.
Eric Prestel, Post-doctoral fellow 2012.
Hector Bautista, Post-doctoral fellow 2012.
Pierre Flores, PhD student 2011-2014.
Charlotte Cousin, PhD student 2010-2014.
Olivier Borkowski, PhD student 2009-2013.
Magalie Celton, PhD student 2008-2011.
Safta De Hillerin, PhD student 2009-2011.
Ludovica Cotta-Ramusino, Post-doctoral fellow 2008-2010.
Nacim Meslem, Post-doctoral fellow 2008-2010.
Fadia Bekkal Bricki, Post-doctoral fellow 2006-2008.
Elodie Marchadier, PhD student 2006-2009.
Catherine Tanous Healy, Post-doctoral fellow 2007-2008.