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Network analysis of bacterial multi-cellular patterning (Bacterial Patterns)
Start date: Oct 1, 2010, End date: Sep 30, 2014 PROJECT  FINISHED 

Defining the mechanisms by which cells cooperate to form complex structures and a common function is a fundamental problem in both developmental biology and socio-biology. Cooperative interactions among bacteria are a relatively simple, yet medically important, model system where this problem can be explored in its full generality. Specifically, bacterial growth on surfaces is often accompanied by formation of complex patterns and increased resilience to diverse external insults. The importance of multiple co-existing cellular differentiated states and of specific cell signaling processes, to spatial patterning and development of bacterial communities has been demonstrated in several systems, including the well-characterized microbe, Bacillus subtilis. However, the nature of these interactions and the way they control the spatial organization of differentiation and patterning is unclear. Specifically, we do not understand (1) when and where are genes and cell fates expressed? (2) What is the spatial organization of cell fates? (3) How does the interaction between fates give rise to spatial order? Here, we suggest addressing these questions by utilizing a novel light-activated gene expression system. This will be used to control the spatial and temporal gene expression profile of a library of patterning-related genes. Time-lapse fluorescence microscopy will be used to monitor the dynamic expression of relevant reporters in wild-type and spatially perturbed backgrounds. We will use mathematical modeling to integrate the results into a predictive model of pattern formation and community development. My previous experience in mathematical modeling of spatial systems, and experimental background in developmental genetics, microbiology and advanced microscopy provides a well suited background to successfully pursue this important problem.
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