Pau Rué

I am a mathematician with a doctoral degree in applied physics. During my PhD, I focused on the analysis of the transient and stochastic dynamics of a few cellular and cell population processes. I studied, amongst others systems, the regulation of pulsating genetic responses during transient cellular differentiation, the post-translational control of pluripotency in mouse Embryonic Stem (ES) cells, the integration of dynamic external information by cellular signalling networks, and the self-organised spatio-temporal population dynamics of bacterial communities that lead to formation of complex structures in biofilms.

I have a broad range of scientific interests spanning across the fields of mathematics, physics and developmental biology. I am particularly interested in understanding the mechanisms regulating the dynamics of cell fate decision making during embryo development. My current research interests are in the molecular and physical mechanisms driving information processing during early embryonic development.

Current projects

Regulation of pluripotency in mouse Embryonic Stem cells

ES cells are cells derived from the epiblast tissue in inner cell mass of the mammalian blastocyst and are characterized by two distinctive aspects: they are pluripotent (can differentiate to any adult cell type), and they can self-renew indefinitely in culture. Both properties make ES cells appealing from both the biomedicine and developmental biology points of view. Although pluripotency is, in fact, a short transient state of cells in vivo, clonal populations of mouse ES cells are kept in the pluripotent state in vitro thanks to a network of transcription factors involving, among others, Sox2/Oct4, Nanog, Tcf3 and β-catenin.

Based on quantitative data at the single-cell level from our lab, we have recently developed a detailed mathematical model of the pluripotency network interactions. The model focuses on the protein interactions and protein complex formation rather than in gene expression regulation and is able to account for the distributions of mRNA and protein concentrations of the involved factors in different experimental conditions. Our results suggest that the function of the network is to buffer the transcriptional activity of Oct4, which appears to be the main determinant to exit pluripotency. The proposed protein network model explains the mechanisms underlying the gain and loss of function in different mutants and sets a theoretical framework for further investigation of pluripotency regulation.

Fig1

Dynamics of the exit from pluripotency and cell fate decision making in ES cells and the early embryo

Despite the large amount of knowledge that we have accumulated to date about the regulation and control of self-renewal, efficient directed differentiation into specific tissues remains a pending subject. I am interested in understanding the interaction between the dynamics of loss of pluripotency and cellular signalling in fate assignment during the early stages of differentiation of both mouse ES cells in culture and the mouse embryo. Combining quantitative data of gene expression from individual cells from our lab we are studying the importance of the state of the cell when responding to signals, such as BMP, Nodal or Wnt, that are associated to self renewal and/or differentiation. Our initial results support the idea that ES cells have an intrinsic competence towards the neuroectoderm fate when allowed for undirected differentiation. However, in the long term and concomitantly with loss of pluripotency and changes in signalling conditions, these cells transit into competence to become mesendoderm. Together, these preliminary results point to the interplay between the dynamics of the exit from pluripotency and the signalling as a mechanism for balancing proportions of these two excluding fates.

Fig2

Coordination of cell fate decision making during early mammalian embryogenesis

During embryonic development cells coordinate spatiotemporal patterns of gene expression. A prominent example of this coordination is found in the gastrulation of amniotes, where Brachyury, a transcription factor, is synchronously and transiently expressed in a localized population, the Primitive Streak. Even though the current view is that a morphogen gradient drives the spatial arrangement of Brachyury expression, the precise mechanisms controlling timing and coordination of cells remain to be elucidated. We aim to study how population-wise coordination of Brachyury expression is attained in differentiating mouse ES cells, which are known to recapitulate the cellular and molecular events observed in the Primitive Streak. The results of this project will deepen our insight in the mechanisms underlying cellular synchronization during development and may uncover more general principles that govern the way in which mammalian cells coordinate their decisions at the tissue level.

Publications

  1. An interplay between extracellular signalling and the dynamics of the exit from pluripotency drives cell fate decisions in mouse ES cells.
    Trott J, Turner DA, Hayward P, Borchia S, Mateus AM, Rué P and Martinez Arias A
    (in preparation, BioRxiv) [preprint]
    doi: 10.1101/000653
  2. Collective stochastic coherence and synchronizability in weighted scale-free networks.
    Balenzuela P, Rué P, Boccaletti S and Garcia-Ojalvo J
    (submitted to New Journa of Physics) [preprint]
  3. A competitive protein interaction network buffers Oct4-mediated differentiation to promote pluripotency in ES cells.
    Muñoz Descalzo S*, Rué P*, Faunes F, Hayward P, Jakt LM, Balayo T, Garcia-Ojalvo J and Martinez Arias A
    Molecular Systems Biology 9 Article number: 694 (2013).
    doi:10.1038/msb.2013.49
  4. Transient and Stochastic Dynamics in Cellular processes.
    Rué P. Supervisor: Jordi Garcia-Ojalvo J (2013) Doctoral thesis.
    doi:10.6084/m9.figshare.763227
  5. Modeling gene expression in time and space.
    Rué P, Garcia-Ojalvo J
    Annual Review of Biophysics, 43, 605–627 (2013)
    doi:10.1146/annurev-biophys-083012-130335
  6. Correlations between the levels of Oct4 and Nanog as a signature for naïve pluripotency in mouse ES cells
    Muñoz Descalzo S, Rué P, Garcia-Ojalvo J and Martinez Arias A
    Stem Cells 30, 2683–2691 (2012)
    doi:10.1002/stem.1230
  7. Localized cell death focuses mechanical forces during 3D patterning in a biofilm
    Asally M, Kittisopikul M, Rué P, Du Y, Hu Z, Çagatay T, Robinson A, Lu H, Garcia-Ojalvo J, Süel GM
    PNAS 109, 18891 (2012)
    doi:10.1073/pnas.1212429109
  8. Integration of cellular signals in chattering environments
    Rué P, Domedel-Puig N, Garcia-Ojalvo J, Pons AJ
    Progress in biophysics and molecular biology 110, 106 (2012) [preprint]
    doi:10.1016/j.pbiomolbio.2012.05.003
  9. Information Routing Driven by Background Chatter in a Signaling Network
    Domedel-Puig N*, Rué P*, Pons AJ, Garcia-Ojalvo J
    PLoS Comput Biol 7(12): e1002297 (2011)
    doi:10.1371/journal.pcbi.1002297
  10. Gene circuit designs for noisy excitable dynamics
    Rué P and Garcia-Ojalvo J
    Mathematical Biosciences 231, 90-97 (2011) [preprint]
    doi:10.1016/j.mbs.2011.02.013
  11. Optimizing periodicity and polymodality in noise-induced genetic oscillators
    Rué P, Süel GM, Garcia-Ojalvo J
    Physical Review E 83, 061904 (2011) [preprint]
    doi:10.1103/PhysRevE.83.061904
  12. Relaxation dynamics and frequency response of a noisy cell signaling network.
    Rué P, Pons AJ, Domedel-Puig N, Garcia-Ojalvo J
    Chaos 20, 045110 (2010)
    doi:10.1063/1.3524908
  13. The histone variant macroH2A is an epigenetic regulator of key developmental genes.
    Buschbeck M, Uribesalgo I, Wibowo I, Rué P, Martin D, Gutierrez A, Morey L, Guigó R, López-Schier L and Di Croce L
    Nature Structural & Molecular Biology 16, 1074 – 1079 (2009)
    doi:10.1038/nsmb.1665
  14. Simulation methods with extended stability for stiff biochemical Kinetics
    Rué P, Villà-Freixa J and Burrage K
    BMC Systems Biology, 4:110  (2010)
    doi:10.1186/1752-0509-4-110

One thought on “Pau Rué

  1. The knotty question of how a variety of highly complex Cells become synchronously organized into interdependent Organs in an independently functioning Host creature such as human being defies rational reduction to language based logic. There is an alternate non-linguistic methodology possible that delineates the ontological structure of all Being. Since it embraces all possible structural varieties of phenomenal experience with respect to inside and outside the epistemological Knowledge of phenomenal behavior derives from it in structurally consistent ways. This universal methodology cannot be a theoretical belief system since it must find direct confirmation in phenomenal behavior from which all language derives (including mathematics). It takes considerable patient reflection to intuitively grasp this hierarchically nested “System” of delineating the structural dynamics of the cosmic order, then many doors begin to open. How it works in Gene expression is introduced in the article http://www.cosmic-mindreach.com/Gene_Expression.html. There are a variety of related articles freely available on the website. It is a uniquely fascinating approach that can bridge our intuitively integrating right brain frameworks of understanding with our language bound linear rational left brain.

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