Multiscale mechanisms of epithelial patterning and morphogenesis: theory and experiments, funded by Human Frontier Science Program (2009 - 2012), cooperation with Princeton University,
Universit¸ Paris VI, and Max Planck Institute of Molecular Cell Biology and Genetics (Dresden)
Folding of epithelial sheets is one of the most ancient mechanisms leading to the formation of three-dimensional structures during embryogenesis. In a highly simplified picture, epithelial morphogenesis can be separated into two steps. First, inductive signals establish two-dimensional patterns of gene expression across the epithelia. At the next step, these patterns are converted into spatial patterns of force generation and mechanical properties of cells, thus controlling the folding of a sheet into a target morphology. Previous studies of epithelial morphogenesis focused on single genes and small networks, but a systems-level model of morphogenesis in any given experimental context is yet to be developed. In developing such a picture, the key questions are related to the number and identities of involved genes, diversity and dynamics of their expression patterns, mechanisms of pattern formation, and connection between patterning and morphogenesis. We will investigate these questions in the context of the formation of the Drosophila eggshell, an established genetic model of epithelial morphogenesis. Given the highly conserved nature of processes involved in epithelial folding, the tools developed for studies of the Drosophila egg and insights derived from this system will be applicable to a wide range of morphogenetic events.
This will be the first time that genetics (Dresden/Princeton), systems biology (Princeton), cell biology (Dahmann), nonlinear dynamics (Haifa/Princeton), and continuum mechanics (Paris/Haifa) will be brought together to study patterning and morphogenesis in a system highly amenable to genetic manipulations. We will establish a two-dimensional atlas for the expression of dozens of genes involved in eggshell morphogenesis and formulate quantitative models for the formation of these patterns by signaling pathways. We will analyze these models computationally and experimentally test their predictions. Based on live imaging and genetic experiments, we will formulate the hypotheses regarding the connection between patterns of gene expression and the mechanical properties of patterned epithelia. We will explore these hypotheses computationally, using a continuum mechanics approach, and experimentally, using live imaging. The result of this integrative approach will be the first experimentally validated systems-level model for two-dimensional epithelial patterning and resulting folding into a target three-dimensional morphology..
postdoctoral positions are currently filled
Patterns and Defects in Nonlinear Systems, funded
by Minerva Center for nonlinear physics of complex systems (1995 - 2010)
Development of analytical and numerical tools for study of formation
and evolution of patterns in nonlinear systems, in particular, reaction-diffusion
systems and optical feedback devices. Study of distorted patterns and other
media with spontaneously broken symmetry dominated by interaction
and motion of defects.
Mesoscopic hydrodynamics of thin films, funded by Israeli Science Foundation
(2002 - 2006)
The aim of the research is to investigate a class of continuous models bridging the gap between molecular dynamics and conventional hydrodynamics, and applicable at mesoscopic distances from gas-liquid and fluid-solid interfaces. Our approach implies continuum description taking into account in a kinetically and thermodynamically consistent way fluid-fluid and fluid-solid intermolecular interactions.
Motion and stability of contact lines, funded by Israeli Science Foundation
(1997 - 2000)
Study of motion and stability of three-phase boundaries under the influence
of intermolecular forces and transport processes; mechanisms
and scenarios of the interfacial instabilities.
Pattern dynamics in catalytic surface reactions, funded by GIF (1999 -
Exploring new pattern formation processes in catalytic surface reactions,
including effects of surface anisotropy, phase transitions, roughening
and faceting. A cooperative experimental-theoretical project that integrates studies of
microscopic surface structure at the nanometer scale with studies of pattern formation in
the macroscopic range.