Gene Expression Analysis
Our group is working to elucidate the genetic and metabolomic circuits perturbed by the exposure of trace amounts of therapeutics and chemical contaminants such as military explosives. In order to analyze the dynamic relationships between the vast number of biological reactants that may respond to the presence of an external molecular stimulant, powerful techniques must be used. The United States Army is committed to understanding phenomena ranging from the off-target effects of therapeutics to the biological impact of high explosive ordinance contamination on military ranges. The tools for analyzing these complicated and dynamic networks are evolving but are currently restricted to the known relationships of the measured values of the gene products and metabolites. New algorithms designed to elucidate heretofore unknown relationships between these measured quantities. We are turning to Network Science techniques to analyze these enormous and complicated data sets.
We are interested in the expression level of specific genes and small molecule metabolites in response to an environmental exposure to trace amounts of a contaminant or drug. We are using the power of microarray technology to assess the up- and down-regulation of genes at the mRNA level in several different experiments. The information gained from this analysis helps identify “hot spots” of activity in response to a stimulus. The data from a typical experiment consists of a list of genes and metabolites and the corresponding relative expression (up- or down-regulated compared to a control). The significant conclusions are drawn from identifying the relationships between the nodes of these network maps. We are using the bacterium, E coli as a model organism to observe the effect of environmental insults such as RDX and HMX and we’re using human cell lines to study the off-target effects of different pools of siRNA-based therapies to address Heterotopic Ossification. Standard gene expression microarray for the monitoring of gene expression and advanced GCxGC-MS techniques for the assessment of metabolite levels will give us unsurpassed resolution and enable us to document the biological circuits impacted by the contaminant.
At its most fundamental level, Biology is the control and interplay between a vast number coupled chemical reactions. These chemical reactions control the basic processes of life as well as providing rapid response mechanisms to counter a plethora of environmental changes. Network Science involves the study of the relatedness of seemingly disparate phenomena.