Systems Biology

james-sharpoe
Multicellular Systems Biology

Group Structure

GROUP LEADER:
James Sharpe (ICREA Research Professor)
STAFF SCIENTIST:
Jim Swoger
POSTDOCTORAL FELLOWS:
Neus Martínez, Andreea Munteanu, Marco Musy, Noemí Carranza, Xavier Diego, Koh Onimaru
TECHNICIANS:
Alexandre Robert, Lucia Russo, Martina Niksic
PhD STUDENTS:
Luciano Marcon, Gaja Lesnicar-Pucko, Jelena Raspopovic, Juergen Mayer, Alba Jiménez, Manu Uzkudun

Summary

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). (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).

(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 (Nature Methods, 5:609-12, 2008).

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Research Projects

  • Computational modelling of vertebrate limb development as an example of organogenesis. A variety 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.
  • 3D and 4D imaging of developmental processes. The model systems we have worked on recently include mouse, chick, zebra fish and Drosophila embryos. The imaging technologies include mesoscopic imaging, such as OPT and SPIM, and time-lapse multiphoton (in-ovo imaging of chick embryogenesis).
  • 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 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

  1. Storer M, Mas A, Robert-Moreno A, Pecoraro M, Ortells M, Di Giacomo V, Yosef R, Pilpel N, Krizhanovsky V, Sharpe J, Keyes William M.
    “Senescence Is a Developmental Mechanism that Contributes to Embryonic Growth and Patterning.”
    Cell, 155(5):1119-1130 (2013).
  2. Cotterell J, Sharpe J.
    “Mechanistic explanations for restricted evolutionary paths that emerge from gene regulatory networks”
    PLoS ONE, 8(4):e61178 (2013).
  3. Coelho FM, Natale D, Soriano SF, Hons M, Swoger J, Mayer J, Danuser R, Scandella E, Pieczyk M, Zerwes HG, Junt T, Sailer AW, Ludewig B, Sharpe J et al.
    “Naive B cell trafficking is shaped by local chemokine availability and LFA-1-independent stromal interactions.”
    Blood, 121(20):4101-4109 (2013)
  4. Sanders PG, Cotterell J, Sharpe J, Isalan M.
    “Transfecting RNA quadruplexes results in few transcriptome perturbations.”
    RNA Biology, 10(2):205-10 (2013).
  5. Eriksson AU, Svensson C, Hörnblad A, Cheddad A, Kostromina E, Eriksson M, Norlin N, Pileggi A, Sharpe J, Georgsson F, Alanentalo T, Ahlgren U.
    “Near infrared optical projection tomography for assessments of beta-cell mass distribution in diabetes research.”
    Journal of Visualized Experiments, (71):e50238 (2013).
  6. Degenkolbe E, König J, Zimmer J, Walther M, Reißner C, Nickel J, Plöger F, Raspopovic J, Sharpe J, Dathe K, Hecht JT, Mundlos S, Doelken SC, Seemann P.
    “A GDF5 Point Mutation Strikes Twice – Causing BDA1 and SYNS2.”
    PLoS Genetics, 9(10):e1003846 (2013).