Real Time Functional Genomics of Metabolism/Cell Arrays

Project Details


DESCRIPTION (provided by applicant): The tools of modern biology are revolutionizing biomedical research, enabling an exponential growth in the
acquisition of data regarding genes, proteins, and their structures and
functions in normal and diseased states. Among these advances, the ability to
monitor profiles of genes, and to a lesser extent, protein expression
accurately, and on a large scale are notable. However, it is often not easy to
correlate the trends and relationships observed in normal or abnormal states to
the phenotype resulting from the gene expression profile. For physiological
states involving metabolic derangements, gene expression profiling does not
fully explain the complex molecular mechanisms involved. Thus, in order to
develop a comprehensive understanding of metabolic states, it is essential to
understand both the gene expression events as well as the cytoplasmic events
that control changes in metabolites. The proposed research seeks to accomplish
the following: (1) To determine the genes whose expression is altered by
molecular mediators of the stress response and to generate green fluorescence
protein (GFP)-tagged expression constructs of these genes; (2) To use
microfabricated and microfluidic techniques for developing a living cell array
systems where differentiated cells can be cultivated and exposed to multiple
inputs; (3) To obtain temporal gene expression profiles using the living cell
array that has been exposed to combinatorial mixtures of stress mediators that
closely mimics the physiological stress response and to use this information to
predict the molecular events that determine the cell's progression to recovery
or failure during stress. This proposal is an interdisciplinary project that
integrates scientific inputs from biology, engineering, and computational
methods. Each element of the proposal is integral to the success of the overall
project and we anticipate that this will provide excellent training to the
postdoctoral fellow and graduate students working on this project. The results
should provide valuable new information on the molecular mechanisms governing
metabolic states, which will be disseminated via peer-reviewed publications and
presentations at national conferences. In summary, the proposed work seeks to
provide fundamental research and a base of personnel equipped to solve problems
in fields such as metabolic engineering where complex biological phenomena are
under investigation.
Effective start/end date2/1/021/31/07


  • National Institute of General Medical Sciences: $294,100.00


  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Genetics
  • Molecular Biology
  • Biochemistry


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