Friday, October 16, 2009 12:00pm Natural Sciences II, Rm 3201
Abstract:
The cellular microenvironment controls the behavior of individual cells and their organization into multicellular structures. Uncovering how the microenvironment instructs the dynamical assembly of multicellular structures is a fundamental challenge in biology with profound implications in applications, such as tissue engineering and regenerative medicine. My lab uses quantitative experimental analysis and systems-level modeling to uncover design principles for engineering multicellular patterns and structures. I will describe the insights emerging from our studies of two model multicellular systems: the nematode C. elegans and human epithelial cell communities.
C. elegans provides a unique test bed for developing systems-level predictive models of multicellular patterning. We have developed a computational framework to construct a “phase diagram” of multicellular phenotypes. This phase diagram represents all the multicellular patterns predicted to occur in response to perturbing the underlying regulatory network. Unexpectedly, the predicted phenotypes are observed experimentally not only in C. elegans, but also exclusively in other species. Thus, the phase diagram offers a framework for tracing systematically how the molecular network has diversified during the evolution of C. elegans and related species.
Predicting the evolutionary trajectories of multicellular phenotypes is of interest not only in model organisms, but also in human cell systems. Misdirected evolution of multicellular phenotypes is the basis of diseases, such as cancer. Thus, we are applying automated single-cell imaging and micropatterning to better understand the assembly, disassembly and growth of human multicellular epithelial structures. Our results reveal how the quantitative interplay between cell-cell contact and global soluble cues regulates epithelial population growth and aggregation dynamics. I will discuss how these findings advance our current understanding of cancer development and provide design strategies for tissue engineering applications.
About the Speaker:
Anand Asthagiri is an Assistant Professor of Chemical Engineering at the California Institute of Technology. His research focuses on the quantitative analysis of biomolecular networks, integrating both experimental and computational work. His lab studies a broad array of biological systems, ranging from yeast to multicellular patterning in the worm C. elegans and human cells. His honors include the Concern Foundation Award for Cancer Research and appointment to the Editorial Board of PLoS Computational Biology. More information is available at http://www.che.caltech.edu/groups/ara/.