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Systems Biology
We are primariliy interested in determining design principles of genetic regulatory networks (Gene
Circuit Design Principles).
Gene Circuit Design Principles
The genes and gene products involved in the response to a signal make up a genetic regulatory circuit, or gene circuit. The designs of gene circuits exhibit diversity in Nature.
Can we explain the diversity, or is it a result of historical accident?
One way to address the problem is by comparing model networks according to
proposed evolutionary criteria, and seeing whether there are classes of models that may confer
evolutionary advantage. We have been applying such a
procedure to study design principles of gene circuits, using mathematically
controlled comparisons. We are additionally developing traditional biophysical models of specific systems in E. coli.
Previous theoretical work has concentrated on gene circuits that involve just one transcription factor (Wall et al, 2003; Wall et al, 2004). Recently, we have begun to study design principles of gene circuits with two transcription factors, beginning with circuits that exhibit a feed-forward loop pattern of TF-DNA interactions. We are also developing detailed models of specific
We are also continually surveying information on transcription factors in E. coli. The information is being compiled in a database called EcoTFs (URL). The current version of the database was compiled for a review article in which we summarized our understanding of the design of gene circuits in bacteria (Wall et al, 2004).
Gene Expression Analysis
Recent technology
enables
biologists
to simultaneously assay the levels of all types of mRNA extracted from a cell culture. The
central device is a microarray that consists of spots of , e.g., single-stranded cDNA or
oligomers that complement the mRNA of interest. According to the method of mRNA labeling,
fluorescent, colorimetric, or radiological assays are used to measure the amount of mRNA that
hybridizes to the DNA at each spot on the array. If the DNA for all transcribed genes is on
the array, the result is a genome-wide assay of global gene expression in the culture.
We have written the SVDMAN software for singular
value
decomposition analysis of gene expression data (abstract; software). We have also written a book
chapter that explains key practical elements of the use of SVD for analysis gene expression
data (pdf; html).
Michael Wall / mewall@lanl.gov
Los Alamos National Laboratory,
CCS-3 MS B256,
Los Alamos NM 87545
tel: 505.665.4209 / fax: 505.667.1126
Last modified Monday, 29-Jun-2009 16:53:20 MDT