Intercellular Interactions and Dynamics of Morphogenesis.

University Of California-Santa Barbara, Santa Barbara CA

Investigators

Abstract

In this project, the PI will develop an intermediate, cell and tissue-level description of tissue and organ morphogenesis that would on one side connect to specific molecular pathways and on the other to the macroscopic phenotypes, thus bridging the gap between the molecular and organismal scales. On this level developmental processes directly involve physical interactions and physics ideas regarding collective phenomena and pattern formation. The PI will develop theoretical models that explain existing experimental observations and generate falsifiable quantitative hypotheses, which will guide new experiments with the long-term goal of elucidating dynamics of morphogenesis. The project will focus on several model systems where extensive experimentally acquired knowledge is available. Specifically, the proposed project will: 1) Investigate the dynamics of cell rearrangement that drives germ-band extension in Drosophila embryo. Based on the quantitative analysis of time-lapse fluorescent microscopy data from T. Lecuit's lab (IBDM, Marseille) the PI will formulate and analyze models of stress and planar cell polarization-dependent mechanical remodeling of cellular cytoskeleton and intercellular adhesion, which causes convergent extension of epithelial tissue. 2) Develop a model of pattern formation in the process of hair-cell differentiation in the avian cochlea. The PI will specifically address the dynamical interplay of lateral inhibition, due to Notch/Delta cell-contact signaling, with cell division and rearrangement that modify tissue morphology. The PI will collaborate with D. Sprinzak (Tel Aviv U) in the design of an experimental investigation of this phenomenon and in the interpretation of the results. 3) Develop a model of intercellular contact signaling mediated by Fat/Ds cell-adhesion proteins, which have been implicated in cell polarity and regulation of growth in Drosophila imaginal discs. The PI will carry out quantitative analysis of the effects of clonal genetic perturbations using extensive existing data from K. Irvine's lab (HHMI and Rutgers), compare results with model predictions and use the model to design new experiments. The PI will collaborate with D. Sprinzak (Tel Aviv U) on the design of the "bottom-up" synthetic reconstruction study of the Fat/Ds signaling. The PI will work with physics students encouraging and guiding their research on biology problems. As a member of the Kavli Institute for Theoretical Physics (KITP), the PI coordinates the Interdisciplinary Biology Initiative that runs programs designed to break barriers between disciplines. The PI will expand these interdisciplinary activities to include, in collaboration with CNSI and MCD Biology Dept on the UCSB campus, a summer experimental research course on the subject of "Dynamics of Development". This course, to be held in 2013, will be the inaugural session of the Santa Barbara Advanced School of Quantitative Biology that is being set up by the PI. The course will teach physics and biology students how quantitative methods and ideas can be applied to the study of animal development.