# Jacques-Alexandre SEPULCHRE

Network dynamics can be analysed with the tools of nonlinear physics, e.g. the concepts of stability, bifurcation, multistationarity, excitability, chaos, etc.

My current research activities comprise the studies of :

- The modeling of intracellular signaling, including the role of retroactivity

- The metabolico-genetic regulation of virulence factors in pathogenic bacteria
- The response of molecular regulatory networks to time-periodic stimulations
- Linear response in chaotic dynamical networks

List of publications

Edited books

[1] *Peyresq Lectures on Nonlinear Phenomena, vol. II*, eds. J-A Sepulchre and J-L Beaumont (World

Scientific, Singapore, 2003).

[2] *Peyresq Lectures on Nonlinear Phenomena, vol. III*, eds. F. Bouchet, B. Audoly, and J-A Sepulchre

(World Scientific, Singapore 2012).

Articles in international refereed journals

[3] J.P. Antoine, D. Lambert and J.A. Sepulchre, Classical Yang-Mills Fields with Conformal Invariance

: from exact solutions to qualitative analysis, *Class. Quantum Grav. *6 (1989) 295-310.

[4] A. Destexhe, J.A. Sepulchre and A. Babloyantz, A comparative study of the experimental

quantification of deterministic Chaos. *Phys. Lett. A *132 (1988) 101-106.

[5] J.A. Sepulchre, G. Dewel and A. Babloyantz, Propagation into Unstable States : The Direct Hopf

Bifurcation, *Phys. Lett. A *147 (1990) 380- 384.

[6] A. Babloyantz and J.A. Sepulchre, Target and Spiral Waves in Oscillatory Media in the Presence

of Obstacles, *Physica D *49 (1991) 52-60.

[7] J.A. Sepulchre and A. Babloyantz, Propagation of target waves in the Presence of Obstacles,

*Phys. Rev. Lett. *66 (1991) 1314-1317.

[8] J.A. Sepulchre and A. Babloyantz, Motions of Spiral Waves in Oscillatory Media and in Presence

of Obstacles, *Phys. Rev. E *48 (1993) pp.187-195.

[9] J.A. Sepulchre and A. Babloyantz, Controlling Chaos in a Network of oscillators, *Phys. Rev. E*

48 (1993) pp.945-950.

[10] R.S. MacKay and J.A. Sepulchre, Multistability in Networks of weakly Coupled Bistable Units,

*Physica D *82 (1995) pp. 243-254.

[11] J.A. Sepulchre and P. Gaspard, Rotational effect on the lifetimes of molecular resonances, *J.*

*Chem. Phys. *102 (1995) pp.6727-6734.

[12] Babloyantz, C. Lourenço and J-A. Sepulchre, Control of chaos in delay differential equations, in

a network of oscillators and in model cortex, *Physica D *86 (1995) pp.274-283.

[13] J.A. Sepulchre and R. S. MacKay, Localised oscillations in conservative or dissipative networks

of weakly coupled autonomous oscillators, *Nonlinearity *10 (1997) pp. 679-713.

[14] J-A Sepulchre and R S MacKay, Discrete breathers in disordered media, *Physica D *113 (1998)

pp. 342-345.

[15] R S MacKay and J-A Sepulchre, Stability of discrete breathers, *Physica D *119 (1998) pp.

148-162.

[16] J.A. Sepulchre and V.I. Krinsky, Bistable reaction-diffusion systems can have robust zero-velocity

fronts, *CHAOS *10 (2000) pp. 826-833.

[17] T. Ahn, R.S. MacKay and J-A Sepulchre, Dynamics of relative phases and generalised multibreathers,

*Nonlinear Dynamics *25 (2001) pp. 157-182.

[18] R.S. MacKay and J-A Sepulchre, Effective Hamiltonian for traveling discrete breathers, J.Phys.

A : Math. and Gen. 35 (2002) pp. 3985-4002.

[19] B. Cessac and J-A. Sepulchre, “Stable resonances and signal propagation in a chaotic network of

coupled units”, Phys. Rev. E 70, 056111, (2004).

[20] M. Kastner and J-A. Sepulchre, Effective Hamiltonian for travelling discrete breathers in the

FPU chain, *Disc. and Cont. Dyn. Sys. B *(2005) p. 719-734.

[21] B. Cessac and J-A Sepulchre, Transmitting a signal by amplitude modulation in a chaotic network,

*CHAOS *16 (2006) 013104-1/12.

[22] B. Cessac and J-A Sepulchre, “Linear response, susceptibility and resonances in chaotic toy

models", *Physica D *225 (2007) 13-28.

[23] J-A Sepulchre, S. Reverchon and W. Nasser, Modeling the onset of virulence in a pectinolytic

bacterium, *J. Theor. Biol. *244 (2007) 239–257.

[24] A. Ventura, J-A Sepulchre and S. Merajver, “A hidden feedback is revealed in signaling cascades",

*PLoS comput biol *4(3) (2008) :e1000041 (and Supp. info. S1-S7).

[25] A. Cournac and J-A Sepulchre, “Simple molecular networks that respond optimally to timeperiodic

stimulation", *BMC Systems Biology *(2009) 3 : 29 doi :10.1186/1752-0509-3-29.

[26] W.D. Kepseu, P. Woafo and J-A. Sepulchre, “Dynamics of the transition to pathogenicity in

*Erwinia chrysanthemi*", *Journal of Biological Systems *Vol. 18, No. 1 (2010) 1–31

[27] W.D. Kepseu, J-A. Sepulchre, S. Reverchon and W. Nasser, “Toward a quantitative modeling of

the synthesis of the pectate lyases, essential virulence factors in *Dickeya dadantii*”, *J. Biol. Chem.*

285 (37) (2010) pp. 28565-28576.

[28] M.L. Wynn, A.C. Ventura, J.A. Sepulchre, H.J. Garcia, S.D. Merajver, Kinase inhibitors can

produce off-target effects and activate linked pathways by retroactivity, *BMC Systems Biology*

(2011) 5 :156 doi :10.1186/1752-0509-5-156.

[29] J.A. Sepulchre, S. Merajver, A.C. Ventura, Retroactive Signaling in Short Signaling Pathways.

*PLoS ONE *7(7) (2012) : e40806. doi :10.1371/journal.pone.0040806

[30] J.A. Sepulchre, A.C. Ventura, Intrinsic negative feedbacks in MAPK signaling cascades lead to

bistability and oscillations, *Acta Biotheoretica *Volume 61, Issue 1 (2013), Page 59-78.

Book chapters

[31] J.A. Sepulchre and A. Babloyantz, Spiral and Target Waves in Finite and Discontinuous Media,

in : *Chemical Waves and Patterns*, edited by R. Kapral and K. Showalter (Kluwer,Dordrecht,1994)

pp.191-217.

[32] J.A. Sepulchre, Energy barriers in coupled oscillators : from discrete kinks to discrete breathers,

in *Localization and Energy Transfer in Nonlinear Systems*, eds. L. Vazquez, M. Zorzano and R.S.

MacKay, (World Scientific, Singapore, 2003) pp. 102-129.

[33] W. Kepseu, F. Van Gijsegem and J.A. Sepulchre, Modelling the onset of virulence in pathogenic

bacteria, in *Bacterial Molecular Networks : Methods and protocols*, eds. D. Thieffry, A. Toussaint

and J. van Helden, Methods in Molecular Biology, vol. 804 (2011) DOI 10.1007/978-1-61779-361-5

25.

Conference proceedings

[34] A. Babloyantz and J.A. Sepulchre, Front Propagation into Unstable Media : A Computational

Tool in : *Nonlinear Wave Processes in Excitable Media*, edited by A.V. Holden, M. Markus and

H.G. Othmer, (Plenum Press, New York, 1989) NATO ASI Series B Vol. 244, pp. 343-350.

[35] J.A. Sepulchre and A. Babloyantz, Spatio-temporal Patterns and Network Computation in :

*Self-Organization, Emerging Properties and Learning*, edited by A. Babloyantz, (Plenum Press,

New York, 1991) ARW Series, pp. 1-20.

[36] J.A. Sepulchre, A. Babloyantz and L. Steels, Path Finding with Nonlinear Waves. in : *Artificial*

*Neural Networks*, edited by T. Kohonen, K. Makisara, O. Simula and J. Kangas (Elsevier, Amsterdam,

1991) pp.1265-1268.

[37] A. Babloyantz and J.A. Sepulchre, Path finding with a network of oscillators, in : *Evolution of*

*Dynamical Structures in Complex Systems*, edited by R. Friedrich and A. Wunderlin, (Springer-

Verlag, Berlin, 1992) pp. 313-320.

[38] A. Babloyantz and J.A. Sepulchre, Information processing by spatio-temporal chaotic networks,

in : *Proceedings of the International Conference on Artificial Neural Networks*, edited by S. Gielen

and B. Kappen (Springer-Verlag,London,1993) pp.670-675.

[39] J.A. Sepulchre and R.S. MacKay, Lattices of bistable Chua circuits with large coupling resistance,

in *Proceedings of the 3rd international specialist workshop on nonlinear dynamics of electronic*

*systems*, edited by P. Kennedy, (University College Dublin, 1995) pp.295-298.

[40] M.L. Wynn, A.C. Ventura, H. Garcia, J.A. Sepulchre, S.D. Merajver Elucidating the role

of retroactive signaling and kinase inhibitors on off-target drug effects *Cancer Research *71 (8

Supplement), (2011) 4907

[41] M.L. Wynn, A.C. Ventura, J.A. Sepulchre, H. Garcia, S.D. Merajver The natural enzyme

sequestration in signaling cascades provides inherent opportunities for off-target effects induced by

kinase inhibitors *Cancer Research *72 (8 Supplement), (2012) 4925

Articles submitted or in revision

[42] W. Kepseu, W. Nasser and J.A. Sepulchre, Modelling the expression of *pel *genes in *Dickeya*

*dadantii *using a mass action law-based model., in revision from subm. to J. of Theor. Biol.

[43] S. Catozzi, JP Di Bella, AC Ventura and J-A Sepulchre, Signaling cascades transmit informations

downstream and upstream but unlikely simultaneously, submitted to BMC Systems Biology.