References of "Bullinger, Eric"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailCell invasion in the spheroid sprouting assay: a spatial organisation analysis adaptable to cell behaviour.
Blacher, Silvia ULg; Erpicum, Charlotte ULg; Lenoir, Benedicte et al

in PLoS ONE (2014), 9(5), 97019

The endothelial cell spheroid assay provides a suitable in vitro model to study (lymph) angiogenesis and test pro- and anti-(lymph) angiogenic factors or drugs. Usually, the extent of cell invasion ... [more ▼]

The endothelial cell spheroid assay provides a suitable in vitro model to study (lymph) angiogenesis and test pro- and anti-(lymph) angiogenic factors or drugs. Usually, the extent of cell invasion, observed through optical microscopy, is measured. The present study proposes the spatial distribution of migrated cells as a new descriptor of the (lymph) angiogenic response. The utility of this novel method rests with its capacity to locally characterise spheroid structure, allowing not only the investigation of single and collective cell invasion but also the evolution of the spheroid core itself. Moreover, the proposed method can be applied to 2D-projected spheroid images obtained by optical microscopy, as well as to 3D images acquired by confocal microscopy. To validate the proposed methodology, endothelial cell invasion was evaluated under different experimental conditions. The results were compared with widely used global parameters. The comparison shows that our method prevents local spheroid modifications from being overlooked and leading to the possible misinterpretation of results. [less ▲]

Detailed reference viewed: 18 (1 ULg)
Full Text
Peer Reviewed
See detailReview of Computational Systems Biology of Cancer
Bullinger, Eric ULg; Schliemann, Monica

in BioMedical Engineering OnLine (2013), 12(1), 76

Detailed reference viewed: 16 (2 ULg)
Full Text
Peer Reviewed
See detailA feedback control perspective on models of apoptosis signal transduction
Readman, Mark C.; Schliemann, Monica; Kalamatianos, Dimitrios et al

in Chaos, Solitons & Fractals (2013)

Apoptosis is a key regulator for replacing unused, old and damaged cells. Here we analyse three models of apoptosis. We deconstruct these models by linearising the models about the life steady state and ... [more ▼]

Apoptosis is a key regulator for replacing unused, old and damaged cells. Here we analyse three models of apoptosis. We deconstruct these models by linearising the models about the life steady state and applying methods from linear control theory. This control viewpoint uncovers a decentralised control scheme with a clear separation of plant and controller and reveals that the caspase inhibitors act as decentralised phase lead controllers. © 2013 Elsevier Ltd. All rights reserved. [less ▲]

Detailed reference viewed: 19 (5 ULg)
See detailUnderstanding biological heterogeneity via dynamical modelling
Bullinger, Eric ULg

Scientific conference (2012, September 07)

Detailed reference viewed: 20 (5 ULg)
See detailModelling on Multiple Scales
Bullinger, Eric ULg

Scientific conference (2012, June 19)

Detailed reference viewed: 16 (3 ULg)
See detailCompréhension de Systèmes Biologiques par la Modélisation Dynamique
Bullinger, Eric ULg

Scientific conference (2012, May 25)

Detailed reference viewed: 12 (2 ULg)
See detailDecision making in noisy bistable switches A local analysis for non local predictions
Trotta, Laura ULg; Bullinger, Eric ULg; Sepulchre, Rodolphe ULg

Conference (2012, March)

In this paper, we try to estimate some statistics about the decision making process in a bistable model submitted to noise by studying the local properties of the system around an hyperbolic saddle point ... [more ▼]

In this paper, we try to estimate some statistics about the decision making process in a bistable model submitted to noise by studying the local properties of the system around an hyperbolic saddle point. Despite the fact that the saddle is not an equilibrium point of the stochastic system, we show that a local approach is still instructive. Under appropriate assumptions, the system can be reduced to an Orsntein-Uhlenbeck process whose dynamics depend on the properties of the saddle point. Yet, Orstein-Uhlenbeck processes have been used to study decision making under uncertainty in a broad variety of fields including statistics and cognitive neurosciences . [less ▲]

Detailed reference viewed: 27 (3 ULg)
See detailIntroduction to Systems Biology
Bullinger, Eric ULg; Kalamatianos, D.; Huber, Heinrich

Scientific conference (2012)

Detailed reference viewed: 11 (2 ULg)
Full Text
Peer Reviewed
See detailRobustness-based model validation of an apoptosis signalling network model
Schliemann, Monica ULg; Findeisen, Rolf; Bullinger, Eric ULg

in Proceedings of the 16th IFAC Symposium on System Identification, Brussels, Belgium, 11–13 July 2012 (2012)

Models of intracellular biochemical reaction networks are difficult to parameterise due to the low number of quantitative time series experimental values. Therefore, model validation or invalidation plays ... [more ▼]

Models of intracellular biochemical reaction networks are difficult to parameterise due to the low number of quantitative time series experimental values. Therefore, model validation or invalidation plays an important role, as it allows to check qualitatively whether a model structure is suited or not to reproduce qualitatively the experimental findings. This paper analyses the robustness of an experimentally validated polynomial differential equation model of TNF-induced pro-and anti-apoptotic signalling. The bistability of the median model is shown robust to large single parameter variations. Only two parameters (XIAP and Procaspase-3 production rates) are shown to be fragile, in particular when changed simultaneously. Therefore, the model seems valid from the point of view of robustness analysis of the bistability. Many biological experiments quantify average concentrations or the percentage of viable cells, while other methods such as microscopy-based experiments observe single cells. The integration of single cell and cell population behaviour of TNF-induced pro- and anti-apoptotic signalling has been achieved via a cell ensemble model, whose robustness is also analysed here. We show that within the cell population there are cells with not only quantitative differences, but also qualitative ones. In particular, all cells are not bistable. The degree of robustness applicable for the median cell is expanded to combine mono- and bistable models. This measure, applied solely to the two-dimensional subspace of fragile parameters, is shown to correlate well with the time of death. While robustness of bistability can serve for model validation of the median cell model, it cannot for the model of the cell population. [less ▲]

Detailed reference viewed: 16 (5 ULg)
Full Text
Peer Reviewed
See detailHeterogeneity Reduces Sensitivity of Cell Death for TNF-Stimuli
Schliemann, Monica ULg; Bullinger, Eric ULg; Borchers, Steffen et al

in BMC Systems Biology (2011), 5

Background Apoptosis is a form of programmed cell death essential for the maintenance of homeostasis and the removal of potentially damaged cells in multicellular organisms. By binding its cognate ... [more ▼]

Background Apoptosis is a form of programmed cell death essential for the maintenance of homeostasis and the removal of potentially damaged cells in multicellular organisms. By binding its cognate membrane receptor, TNF receptor type 1 (TNF-R1), the proinflammatory cytokine Tumor Necrosis Factor (TNF) activates pro-apoptotic signaling via caspase activation, but at the same time also stimulates nuclear factor kappaB (NF-kappaB)-mediated survival pathways. Differential dose-response relationships of these two major TNF signaling pathways have been described experimentally and using mathematical modeling. However, the quantitative analysis of the complex interplay between pro- and anti-apoptotic signaling pathways is an open question as it is challenging for several reasons: the overall signaling network is complex, various time scales are present, and cells respond quantitatively and qualitatively in a heterogeneous manner. Results This study analyzes the complex interplay of the crosstalk of TNF-R1 induced pro- and anti-apoptotic signaling pathways based on an experimentally validated mathematical model. The mathematical model describes the temporal responses on both the single cell level as well as the level of a heterogeneous cell population, as observed in the respective quantitative experiments using TNF-R1 stimuli of different strengths and durations. Global sensitivity of the heterogeneous population was quantified by measuring the average gradient of time of death versus each population parameter. This global sensitivity analysis uncovers the concentrations of Caspase-8 and Caspase-3, and their respective inhibitors BAR and XIAP, as key elements for deciding the cell's fate. A simulated knockout of the NF-kappaB-mediated anti-apoptotic signaling reveals the importance of this pathway for delaying the time of death, reducing the death rate in the case of pulse stimulation and significantly increasing cell-to-cell variability. Conclusions Cell ensemble modeling of a heterogeneous cell population including a global sensitivity analysis presented here allowed us to illuminate the role of the different elements and parameters on apoptotic signaling. The receptors serve to transmit the external stimulus; procaspases and their inhibitors control the switching from life to death, while NF-kappaB enhances the heterogeneity of the cell population. The global sensitivity analysis of the cell population model further revealed an unexpected impact of heterogeneity, i.e. the reduction of parametric sensitivity. [less ▲]

Detailed reference viewed: 65 (16 ULg)
See detailControl in Biological Systems - from Intercellular Signalling to the Organism
Bullinger, Eric ULg

Scientific conference (2011, September 16)

Detailed reference viewed: 11 (0 ULg)
Full Text
See detailLa biologie intégrative ou biologie systémique
Bullinger, Eric ULg; Olivier, Jacques

Diverse speeche and writing (2011)

Le décryptage du génome de nombreux organismes a montré que la seule connaissance de la structure des gênes ne suffisait pas à expliquer le fonctionnement d’une cellule, d’un organisme ou d’un individu ... [more ▼]

Le décryptage du génome de nombreux organismes a montré que la seule connaissance de la structure des gênes ne suffisait pas à expliquer le fonctionnement d’une cellule, d’un organisme ou d’un individu. Un même gêne peut jouer un rôle différent selon le contexte physiologique dans lequel il s’exprime ou bien encore, une même fonction peut être assurée par des assemblages de gênes différents. Il semble donc que la biologie doive à présent quitter le réductionnisme qui était le sien pour une vision plus intégrative qui fait la part belle aux réseaux d’interactions entre les différents acteurs (gênes, protéines, métabolites). C’est le domaine de la biologie intégrative ou biologie systémique. Rencontre avec Eric BULLINGER, ingénieur spécialiste des systèmes et de la modélisation à l’Université de Liège et qui intervient désormais dans la biologie. [less ▲]

Detailed reference viewed: 27 (3 ULg)
See detailTopics in Mathematical and Systems Biology
De Leenheer, Patrick; Bullinger, Eric ULg

Scientific conference (2011)

Detailed reference viewed: 8 (0 ULg)
Full Text
Peer Reviewed
See detailFeedback control strategies for spatial navigation revealed by dynamic modelling of learning in the Morris water maze
Fey, Dirk ULg; Commins, Sean; Bullinger, Eric ULg

in Journal of Computational Neuroscience (2011), 30(2), 447-454

The Morris water maze is an experimental procedure in which animals learn to escape swimming in a pool using environmental cues. Despite its success in neuroscience and psychology for studying spatial ... [more ▼]

The Morris water maze is an experimental procedure in which animals learn to escape swimming in a pool using environmental cues. Despite its success in neuroscience and psychology for studying spatial learning and memory, the exact mnemonic and navigational demands of the task are not well understood. Here, we provide a mathematical model of rat swimming dynamics on a behavioural level. The model consists of a random walk, a heading change and a feedback control component in which learning is reflected in parameter changes of the feedback mechanism. The simplicity of the model renders it accessible and useful for analysis of experiments in which swimming paths are recorded. Here, we used the model to analyse an experiment in which rats were trained to find the platform with either three or one extramaze cue. Results indicate that the 3-cues group employs stronger feedback relying only on the actual visual input, whereas the 1-cue group employs weaker feedback relying to some extent on memory. Because the model parameters are linked to neurological processes, identifying different parameter values suggests the activation of different neuronal pathways. [less ▲]

Detailed reference viewed: 19 (9 ULg)
Full Text
Peer Reviewed
See detailDelayed decision-making in bistable models
Trotta, Laura ULg; Sepulchre, Rodolphe ULg; Bullinger, Eric ULg

in Proceedings of the 49th IEEE Conference on Decision and Control (2010, December)

Detailed reference viewed: 129 (65 ULg)
See detailControl in Biological Systems - from Intercellular Signalling to the Organism
Bullinger, Eric ULg

Scientific conference (2010, April 28)

Detailed reference viewed: 7 (0 ULg)