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                                           BIOINFORMATICS COLLOQUIUM
					       College of Science
                                            George Mason University
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		  Measuring Intracellular Molecular Dynamics and Interactions in the Tissue Context 
					      Stephen Lockett, Ph.D.
 
					       Principal Scientist
					    National Cancer Institute

Abstract:
Communications between neighboring cells in large part drive tissue development and 
function, as well as disease-related processes such as tumorigenesis. In order to 
understand the molecular basis of these processes, it is necessary to quantitatively 
analyze the dynamics of specific molecules in adjacent individual cells of intact tissue. 
Two major bottlenecks preventing widespread use of such analyses are the lack of methods 
to determine the mobility and binding constants of specific molecules in living cells and 
the lack of an efficient method to correctly segment all individual, whole cells in 
intact tissue samples.

We are integrating with mathematical modeling a family of quantitative microscopy 
techniques for determining the dynamics and interactions of fluorescence-tagged 
proteins in individual living cells.

For analyzing individual cells in tissue, we have developed semi-interactive software, 
based on dynamic programming to segment each cell or cell nucleus labeled with a 
fluorescent surface marker from 3D microscope images. The software accurately detects 
virtually 100% of cells including irregularly shaped cells containing concavities. 
We have applied the software for analyzing cell-to-cell genetic variability in breast 
cancer and are currently studying the spatial positioning of genes and the relationship 
to gene expression.