Genome-wide analyses of single cell phenotypes using cell microarrays

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Title: Genome-wide analyses of single cell phenotypes using cell microarrays
Author: Narayanaswamy, Rammohan, 1978-
Abstract: The past few decades have witnessed a revolution in recombinant DNA and nucleic acid sequencing technologies . Recently however , technologies capable of massively high -throughout , genome -wide data collection , combined with computational and statistical tools for data mining , integration and modeling have enabled the construction of predictive networks that capture cellular regulatory states , paving the way for ‘Systems biology’ . Consequently , protein interactions can be captured in the context of a cellular interaction network and emergent ‘system’ properties arrived at , that may not have been possible by conventional biology . The ability to generate data from multiple , non -redundant experimental sources is one of the important facets to systems biology . Towards this end , we have established a novel platform called ‘spotted cell microarrays’ for conducting image -based genetic screens . We have subsequently used spotted cell microarrays for studying multidimensional phenotypes in yeast under different regulatory states . In particular , we studied the response to mating pheromone using a cell microarray comprised of the yeast non -essential deletion library and analyzed morphology changes to identify novel genes that were involved in mating . An important aspect of the mating response pathway is large -scale spatiotemporal changes to the proteome , an aspect of proteomics , still largely obscure . In our next study , we used an imaging screen and a computational approach to predict and validate the complement of proteins that polarize and change localization towards the mating projection tip . By adopting such hybrid approaches , we have been able to , not only study proteins involved in specific pathways , but also their behavior in a systemic context , leading to a broader comprehension of cell function . Lastly , we have performed a novel metabolic starvation -based screen using the GFP -tagged collection to study proteome dynamics in response to nutrient limitation and are currently in the process of rationalizing our observations through follow -up experiments . We believe this study to have implications in evolutionarily conserved cellular mechanisms such as protein turnover , quiescence and aging . Our technique has therefore been applied towards addressing several interesting aspects of yeast cellular physiology and behavior and is now being extended to mammalian cells .
URI: http : / /hdl .handle .net /2152 /3967
Date: 2008-08-29

Citation

Genome-wide analyses of single cell phenotypes using cell microarrays. Doctoral dissertation, The University of Texas at Austin. Available electronically from http : / /hdl .handle .net /2152 /3967 .

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