Learn More
Subgenic-resolution oligonucleotide microarrays were used to study global RNA degradation in wild-type Escherichia coli MG1655. RNA chemical half-lives were measured for 1036 open reading frames (ORFs) and for 329 known and predicted operons. The half-life of total mRNA was 6.8 min under the conditions tested. We also observed significant relationships(More)
We have developed a high-resolution "genome array" for the study of gene expression and regulation in Escherichia coli. This array contains on average one 25-mer oligonucleotide probe per 30 base pairs over the entire genome, with one every 6 bases for the intergenic regions and every 60 bases for the 4,290 open reading frames (ORFs). Twofold concentration(More)
Changes in DNA supercoiling are induced by a wide range of environmental stresses in Escherichia coli, but the physiological significance of these responses remains unclear. We now demonstrate that an increase in negative supercoiling is necessary for transcriptional activation of a large subset of osmotic stress-response genes. Using a microarray-based(More)
Phenotypic compound screens can be used to identify novel targets in signaling pathways and disease processes, but the usefulness of these screens depends on the ability to quickly determine the target and mechanism of action of the molecules identified as hits. One fast route to discovering the mechanism of action of a compound is to profile its properties(More)
SMAD6 is a crucial feedback inhibitory regulator of bone morphogenetic protein (BMP)/SMAD signalling. Although little is known regarding the post-transcriptional modification of inhibitory SMADs and the mechanism by which their function is regulated. In this study, using a whole proteomic interaction screen for SMAD6, we identified a large putative E2(More)
The nascent field of systems biology ambitiously proposes to integrate information from large-scale biology projects to create computational models that are, in some sense, complete. However, the details of what would constitute a complete systems-level model of an organism are far from clear. To provide a framework for this difficult question it is useful(More)
Translation initiation is a fine-tuned process that plays a critical role in tumorigenesis. The use of small molecules that modulate mRNA translation provides tool compounds to explore the mechanism of translational initiation and to further validate protein synthesis as a potential pharmaceutical target for cancer therapeutics. This report describes the(More)
Screens using high-throughput, information-rich technologies such as microarrays, high-content screening (HCS), and next-generation sequencing (NGS) have become increasingly widespread. Compared with single-readout assays, these methods produce a more comprehensive picture of the effects of screened treatments. However, interpreting such multidimensional(More)
The use of small molecules to modulate cellular processes is a powerful approach to investigate gene function as a complement to genetic approaches. The discovery and characterization of compounds that modulate translation initiation, the rate-limiting step of protein synthesis, is important both to provide tool compounds to explore this fundamental(More)
The identification of molecular target and mechanism of action of compounds is a key hurdle in drug discovery. Multiplexed techniques for bead-based expression profiling allow the measurement of transcriptional signatures of compound-treated cells in high-throughput mode. Such profiles can be used to gain insight into compounds' mode of action and the(More)
  • 1