Systems Biology


Multicellular Systems Biology

James Sharpe (ICREA Research Professor)
Jim Swoger
Neus Martínez, Andreea Munteanu, Marco Musy, Noemí Carranza, Xavier Diego, Koh Onimaru, Ivica Slavkov, Philiipp Germann
Alexandre Robert, Lucia Russo, Martina Niksic
Jelena Raspopovic, Juergen Mayer, Alba Jiménez, Manu Uzkudun


The Sharpe lab has 2 primary goals:

(1) To further our understanding of organogenesis as a complex system, by bringing together a diverse range of techniques from biology, physics, imaging and computer science. Within this general theme, we focus on two aspects: (a) We are studying a well-characterised standard model of development – the vertebrate limb (using both mouse and chick). The goal is to combine experimental data (especially 3D data sets using optical projection tomography) into a computational framework, so that we can explore and test mechanistic hypotheses about how this example of organogenesis works. Using this approach we are studying both the physical morphogenesis (eg. Boehm et al., 2010, Marcon et al. 2011) and also the genetic patterning mechanisms (eg. Sheth et al., 2012). Our recent success has helped to support the idea that digit patterning is achieved by a Turing reaction-diffusion system (Raspopovic et al., 2014). (b) In addition to this specific model system, we are also interested in the theoretical principles by which gene regulatory networks can create controlled spatial patterns in multicellular contexts (eg. Cotterell et al., 2010), and during 2014 published two further studies on this theme: Schaerli et al. 2014, and Munteanu et al. 2014.

(2) Building on the success of the 3D imaging technique developed within the lab called Optical Projection Tomography (OPT – Science, 296:541, 2002), the other major goal of the lab is to continue developing and improving 3D and 4D imaging technology including the development of time-lapse imaging of mouse limb development in-vitro (eg. Nature Methods, 5:609-12, 2008). Our recent projects include the development of OPTiSPIM (Maeyer et al., 2014).

Research Projects

  • Computational modelling of vertebrate limb development as an example of organogenesis. A number of projects in the lab focus on building models to explore both the control by gene regulatory networks, and also how cellular and tissue mechanics is coordinated to generate the correct shape changes.
  • Morphometrics in development. We are developing novel morphometric techniques for quantifying shape changes of developing tissues and dynamic gene expression patterns.
  • Theoretical models of gene regulatory networks. We are studying the dynamical mechanisms of simple networks capable of multicellular pattern formation, and also exploring how these dynamics could act as constraints during evolution.
  • 3D and 4D imaging of developmental processes. The model systems we have worked on recently include mouse, chick, zebrafish and Drosophila embryos. The imaging technologies include mesoscopic imaging, such as OPT and SPIM, and time-lapse multiphoton (in-ovo imaging of chick embryogenesis).

  • The Sharpe lab is constructing various 2D and 3D computer models of limb development.




    3D mesoscopic imaging technology – OPT and SPIM. We continue to develop technical improvements to mesoscopic imaging technologies, allowing for 3D and 4D data-capture of complex multicellular processes.


Selected Publications

Raspopovic J, Marcon L, Russo L, Sharpe J.
“Modeling digits. Digit patterning is controlled by a Bmp-Sox9-Wnt Turing network modulated by morphogen gradients.”
Science, 345(6196):566-70. doi:10.1126/science.1252960 (2014).

Schaerli Y, Munteanu A, Gili M, Cotterell J, Sharpe J, Isalan M.
“A unified design space of synthetic stripe-forming networks.”
Nature Communications, 5:4905. doi:10.1038/ncomms5905 (2014).

Mayer J, Robert-Moreno A, Danuser R, Stein JV, Sharpe J, Swoger J.
“OPTiSPIM: integrating optical projection tomography in light sheet microscopy extends specimen characterization to nonfluorescent contrasts.”
Optics Letters, 39(4):1053-6. doi: 10.1364/OL.39.001053 (2014).

Nowlan N, Sharpe J.
“Joint shape morphogenesis precedes cavitation of the developing hip joint.”
Journal of Anatomy, 224(4):482-9. doi: 10.1111/joa.12143 (2014).

Munteanu A, Cotterell J, Solé RV, Sharpe J.
“Design principles of stripe-forming motifs: the role of positive feedback.”
Scientific Reports, 4:5003. doi: 10.1038/srep05003 (2014).

Sharpe J.
“Developmental biology: Cells unite by trapping a signal.”
Nature, 515(7525):41-2. doi: 10.1038/nature13933 (2014).