ayout 1 - EMBL Grenoble

EMBL Research at a Glance 2009
Lars Hufnagel
PhD 2001, MPI for Dynamics
and Self-Organisation,
Göttingen.
Postdoctoral research at the
Kavli Institute for Theoretical
Physics, Santa Barbara,
California.
Group leader at EMBL
Heidelberg since 2007.
Dynamics of cell growth and tissue architecture
Previous and current research
We have recently investigated the interplay between the growth of Drosophila wing imaginal discs
and the formation of the Dpp morphogen gradient. Our results suggest a new scenario of size determination,
where disc size is determined relative to the fixed morphogen distribution. Our model
shows that a feedback of mechanical stress on cell growth can compensate for non-uniform distributions
of growth-stimulating morphogens and insures uniform growth throughout the disc.
Furthermore, we have formulated
and analysed a
model describing the interaction
of morphogens with glypicans and have compared its prediction
to measurements of the effect of glypican Dally-like (Dlp) overexpression
on Wingless (Wg) morphogen signalling in Drosophila wing imaginal
discs. The model explains the opposing effect that Dlp
overexpression has on Wg signalling in the distal and proximal regions
of the disc. Our model suggests that Dlp acts by allowing Wg to diffuse
on cell surface while protecting it from loss and degradation, and that
Dlp, rather than acting as Wg co-receptor, competes with receptors for
morphogen binding.
Currently, we are investigating the role of mechanical constraints on cell
growth, apoptosis, orientation of division, intra-tissue rearrangements
and cell differentiation.
Future projects and goals
Our research interests are focussed on the control and regulation of cell
proliferation, apoptosis and cellular rearrangement processes in developing
tissues, with a specific emphasis on epithelial tissues and the role
of mechanical interactions as a regulator.
Two fundamental processes must occur concurrently in tissues during animal development. Firstly,
tissues must grow rapidly to generate the final adult size of the organism, and cells have to stop
growing and dividing once the final size is reached. Secondly, the tissue needs to be specified and
patterned with each cell adopting the appropriate fate and gene expression profile for its position.
Both processes are intrinsically connected and need to be coordinated. Central to the formation
of a tissue is the establishment, maintenance and remodelling of complex cell-cell interactions
that supply mechanical integrity and stability. Tissue growth is a highly dynamic and heterogeneous
process. It involves many spatial and temporal scales, and for a deeper understanding one
has to integrate information on a single cell level with cell-cell interactions and population effects.
Bridging the scales from a single cell to the
whole tissue by combining cell culture and
organ growth experiments with modelling.
We seek to characterise and quantify the spatiotemporal effects of mechanical stress, deformations and fluid flow-induced sheer stress on cell
growth, gene expression and cellular polarity in two-dimensional epithelial tissues. To address this issue, we pursue an interdisciplinary approach
combining classical biological techniques with detailed modelling methods from various fields, ranging from statistical physics to applied
mathematics and computer science. Our research also relies on novel microscopy methods in conjunction with the development of
sophisticated image analysis tools. Furthermore, the group continues its current research on Drosophila wing development and has a specific
interest in the spread of pathogens in epithelial tissues.
Selected references
Brockmann, D. & Hufnagel, L. (2007). Front propagation in reactionsuperdiffusion
dynamics: taming Lévy flights with fluctuations. Phys.
Rev. Lett., 98, 178301
Hufnagel, L., Teleman, A.A., Rouault, H., Cohen, S.M. & Shraiman,
B.I. (2007). On the mechanism of wing size determination in fly
development. Proc. Natl. Acad. Sci. USA, 10, 3835-380
Brockmann, D., Hufnagel, L. & Geisel, T. (2006). The scaling laws of
human travel. Nature, 39, 62-65.
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Hufnagel, L., Kreuger, J., Cohen, S.M. & Shraiman, B.I. (2006). On
the role of glypicans in the process of morphogen gradient
formation. Dev. Biol., 300, 512-522.
Brockmann, D., Hufnagel, L. & Geisel, T. (2005). Dynamics of
Modern Epidemics. In ‘SARS: A Case Study in Emerging Infections’,
McLean, A., May, R., Pattison, J. & Weiss, R. (eds), Oxford
University Press
Hufnagel, L., Brockmann, D. & Geisel, T. (200). Forecast and
control of epidemics in a globalized world. PNAS, 101, 1512–15129