In this project the PI will develop theoretical models that explain existing experimental observations and generate falsifiable quantitative hypotheses that could guide new experiments with the long term goal of defining the mechanisms of size and shape determination in specific model systems. Although the ideas and methods will be general, the project will focus on the development of Drosophila imaginal discs - the larval precursors of adult limbs and organs - where extensive experimentally acquired knowledge is available. Specifically, the proposed project will: 1) Develop a model of mechanical interactions between cells in growing tissue and explore quantitative consequences of non-uniformity and anisotropy in cell growth and of variation in cell properties. 2) Define and solve the inverse problem for mechanical parameter determination for a disordered two-dimensional array of cells. 3) Develop a model of cell contact signaling mediated by proto-cadherins (cell-adhesion molecules) which have been implicated in cell polarity and regulation of growth in Drosophila imaginal discs. The project will involve collaborations with several experimental groups. The PI will use the infrastructure of the existing KITP sponsored local K-12 outreach program to organize science presentations by the graduate research assistants supported by the present application. These presentations for High School student audiences will focus on the exciting opportunities of interdisciplinary research, extending the existing physics-based program. The PI will also establish a cooperative internship that will bring students (working towards their MS-degree equivalent) from Latin America to KITP for six months of research on interdisciplinary problems under his mentorship.
The goal of this interdisciplinary project at the interface of Physics and Biology was to advance understanding of the role of mechanical interactions and contact signaling between cells in the regulation of cell proliferation and epithelial tissue growth. Regulation of cell proliferation is a fundamental process which is critically important in the development of multicellular organisms. The disruption of this process is the central cause of cancer. Yet relatively little has been previously understood about the role of mechanical and contact interactions in growth control: the important gap which this project aimed to fill. Among the key scientific results of the project was the demonstration of the role of mechanical constraint on the rate of epithelial cell division and the quantitative characterization of the dependence of division rate on cell size. The project has also provided the first non-invasive method for inferring the presence of mechanical stress in cells on the basis of cell resolved epithelial tissue images, providing a new powerful tool for the study of the role of mechanics in tissue growth and development. It also led to the formulation of a new model of cell-contact signaling which will guide the next generation of experimental studies of epithelial growth regulation. Another important and successfully fulfilled goal of the project was to advance quantitative approaches to biological phenomena, provide interdisciplinary training to graduate students and post-doctoral researchers and to promote public appreciation of the important conceptual and methodological connections that exists between Physical and Life Sciences.
