Tissue Growth and Morphogenesis: from Genetics to Mechanics and Back (12w5048)
Christian Dahmann (Max Planck Institute of Molecular Cell Biology and Genetics)
James J. Feng (University of British Columbia)
Leonid Pismen (Technion - Israel Institute of Technology)
So far research dealing with the genetic, cellular and tissue aspects of morphogenesis has largely progressed independently, with insufficient conversation among the different communities of scientists. Yet, it is clear from the brief overview above that the problem at hand is multidisciplinary and calls for a coordinated approach that integrates insights and knowledge from the different approaches. One can envision a close coupling of the different length scales via propagation of information in both directions. For example, genetic-molecular pathways may predict or rationalize the abundance of certain signaling molecules such as the Hedgehog. This information can then be utilized on the cellular level to explain apical constriction. In the meantime, intracellular mechanical and geometric cues will affect the reaction-diffusion of active chemical messengers that modifies the genetic-molecular expression in return.
The three organizers come from biology, physics and mechanics backgrounds. From our own work, we are keenly aware of the limitations of each approach to the problem if pursued separately. Dahmann works on experimental observation of pattern formation and morphogenesis during tissue development; Pismen has been studying self-organization and pattern formation in chemical, fluid-mechanical, and biological systems; and Feng, jointly appointed at UBC in Mathematics and Chemical Engineering, has been working on continuum and discrete models on cell mechanics, including polarization, motility and deformation. His group has developed a comprehensive toolkit for simulating complex fluids and soft solids that is being applied to compute cell dynamics. The recently started collaboration among us, in the framework of an interdisciplinary HFSP (Human Frontier Science Program) project on morphogenesis in the egg shell of the fruit fly Drosophila, brought about the realization that a tremendous advantage can be gained in the area of morphogenesis if researchers from different backgrounds are brought together, and shown the wide range of problems to which their methods can be successfully applied, probably after adaptation and fusion with other ideas and techniques. Mathematics is clearly the most important theme that overarches all the relevant work so far.
We expect the following concrete outcomes from the workshop:
(1) To survey the state of the art on tissue growth and morphogenesis, and highlight it as an important emerging area in applied mathematics. Experimentalists will describe recent observations and measurements on processes such as morphogen spreading, collective cell migration, gastrulation movements, dorsal closure, cell sorting, and force sensing. Theoreticians and numerical analysts will summarize the predictive capabilities of their models, including continuum and discrete numerical methods. We will encourage the two sides to "compare notes" and come up with a common understanding of our current knowledge in this area.
(2) To identify the most pressing scientific problems. Experimentalists will underscore phenomena that cannot be readily rationalized or explained. These might include morphogen gradients driving tissue growth, mechanical feedback on gene expression, or forces driving cell sorting. Modelers and simulators will define the limitations of various theoretical and numerical methods, and explore multiscale modeling for prototypical events such as the apical constriction in epithelial invagination, force propagation, chemo-mechanical feedbacks, and the routes to morphological changes.
(3) To develop promising research strategies for the future. In view of the list of high-priority research problems, the workshop will conduct an inventory of the cutting-edge observational, modeling and computational techniques, and suggest the most appropriate approaches to each problem. These can be combinations of existing approaches developed for separate aspects of morphogenesis. For instance, mechanical models for cell deformation can be integrated into kinetic and transport models for the signaling molecules to address the coupling across length and time scales. Or better yet, the discussion may produce completely novel concepts and ideas to be explored in the future.
(4) To facilitate the pursuit of these strategies by initiating interdisciplinary collaborations. We envision broad and lively discussions of all the theoretical developments, computational methodologies and experimental discoveries. Out of the discussions, we hope, collaborations will naturally grow between researchers with complementary skills and expertise. In particular, younger scientists will benefit from direct interactions with more established experts, and from the opportunity to integrate or distinguish themselves in this exciting multi-disciplinary community.
We have compiled a stellar and diverse roster for the workshop. We have invited the mathematical experts on modeling and computations, leading biophysicists specializing in cell-level measurements and characterization, and geneticists and developmental biologists actively exploring the connection between gene expression and tissue mechanics. In the meantime, we have also included a significant number of younger researchers, with the aim of providing them with essential tools and techniques that they would not normally encounter within their own institutions and research groups. So far 32 of the 44 first-round invitees have accepted the invitation pending on determination of the workshop's timing. Many enthusiastically endorsed the idea for the workshop, and some suggested ideas and topics for the workshop that have been incorporated in the above. If time conflict prevents some from attending, we have also compiled a "waiting list" of a dozen people. We are confident that this workshop will gather an exceptionally strong group of scientists. We plan to use the materials of the workshop for a special issue of European Physical Journal ST-DD (Special Topics - Discussions & Debates) where Pismen is an Editor.