Laboratory of the Structure and Function of Living Matter
Cell fate decisions, Signal transduction, Embryonic Stem cells, Self organisation, Physics of Biology, Imaging, Image analysis
We envision biological systems as Living Matter because we are interested in looking at the way in which its fundamental components (genes and proteins) organize themselves in a manner that creates and processes information. A product of this organization is cells, which are the units from which tissues and organs emerge. We are interested in describing and understanding the molecular networks that emerge from the interactions between genes and proteins that enable cells to interact with each other, make decisions about their fates (phenotypes) and self organize in space and time.
A common representation of this process is Waddington’s epigenetic landscape (see Figure below) which portrays trajectories of cells during development towards specific fates, which are thought of as attractors of dynamical systems built by interactions between signal and transcription factor networks.
Our main experimental system at the moment is mouse Embryonic Stem (ES) cells that we see as the basis for an interdisciplinary approach to how cells generate organs and tissues, with a combination of classical genetics, quantitative cell biology, image analysis and modelling. Over the last year we have observed that under controlled experimental conditions mouse ES cells can be coaxed into forming patterned aggregates that mimic many of the events of early embryogenesis including gastrulation. This has opened up a number of novel research avenues that we are exploring at the moment. The picture below shows ES cells bearing a reporter for Wnt signalling in a differentiating colony (left), a gastruloid (center, showing the polarized organization of the signalling event) and in an embryo at the end of gastrulation.
Currently we have four related lines of work:
- Stochastic and deterministic processes in cell fate decisions
- Genetically supervised ‘self-organization’ of ensembles of ES cells
- Experimental and theoretical models of symmetry breaking and axial elongation in early mammalian development
- Integration of Wnt/Notch signalling in development
- Rue, P and Martinez Arias, A. (2015) Cell dynamics and gene expression control in tissue homeostasis and development. Mol. Sys. Biol. 11:792. doi: 10.15252/msb.20145549.
- van den Brink, S., Baillie-Johnson, P., Balayo, T., Hadjantonakis, AK., Nowotschin, S., Turner, DA. And & Martinez Arias, A. (2014) Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse ES cells. Development 141, 4231-4242.
- Turner, DT., Hayward, P., Baillie Johnson, P., Broome, R., Rue, P., Faunes, F. and Martinez Arias, A. (2014) Wnt/ß-catenin and FGF signalling direct the specification and maintenance of a neuromesodermal axial progenitor in ensembles of mouse ES cells. Development 141, 4242-4253.
- Turner, DT., Trott, J., Hayward, P. Rue, P and Martinez Arias, A. (2014) An interplay between extracellular signalling and the dynamics of the exit from pluripotency drives cell fate decisions in mouse ES cells. Biology Open 3, 614-626.
- Turner, DT., MacKenzie, J., Davies, E. and Martinez Arias, A. (2013) Brachyury cooperates with Wnt/ß-Catenin signalling to specify individual cell velocities during Primitive Streak differentiation of mouse ES cells. BMC Biology 13, 63 doi:10.1186/s12915-014-0063-7
- Muñoz-Descalzo, S., Rue, P., Faunes, F., Hayward, P., Jakt, L.M., Balayo, C., Garcia Ojalvo, J. and Martinez Arias, A. (2013) A competitive protein interaction network buffers Oct4-mediated differentiation to promote pluripotency in embryonic stem cells. Mol Syst Biol. 9, 694. doi: 10.1038/msb.2013.49
- Faunes, F., Hayward, P., Muñoz Descalzo, S., Chaterjee, S., Balayo, T., Trott, J., Ferrer-Vaquer, A., Hadjantonakis, AK.,Dasgupta, R. and Martinez Arias, A. (2013) A membrane associated ß-catenin/Oct4 complex is associated with ground state pluripotency in mouse Embryonic Stem Cells. Development 140, 1171-1183.
- Muñoz Descalzo, S., de Navascues, J. and Martinez Arias, A. (2012) Wnt/Noch signaling: an integrated mechanism regulating transitions between cell states. Bioessays 34, 110-118
>> Full list of publications on PubMed