Research findings - CC
Dr. Andy Connolly of Stanford Medical School
Histology of colon tissue
Normal Colon Tissue
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Cancerous Colon Tissue
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- Mathematical modeling of RNA hairpin stability involving temperature, ion strength, and stretching force
- A thermosensor in Salmonella and how scientists altered it and what affects that had on the melting temperature. Pretty close to what we are doing!!
- In Listeria monocytogenes, virulence genes are maximally expressed at 37°C, almost silent at 30°C and controlled by PrfA, a transcriptional activator whose expression is thermoregulated. Here, we show that the untranslated mRNA (UTR) preceding prfA, forms a secondary structure, which masks the ribosome binding region. Mutations predicted to destabilize this structure led to virulence gene expression and invasion of mammalian cells at 30°C. Chemical probing, native gel electrophoresis, in vitro translation, and “compensatory” and “increased stability” mutations demonstrated that the UTR switches between a structure active at high temperatures, and another inactive at low temperatures. Strikingly, when the DNA corresponding to the UTR was fused to gfp in E. coli, bacteria became fluorescent at 37°C, but not at 30°C. This mechanism of posttranscriptional thermoregulation may have important applications.
- Thermosensors and how to engineer them
- We show that the problem of designing RNA sequences that can fold into multiple stable secondary structures can
be transformed into a combinatorial optimization problem that can be solved by means of simple heuristics. Hence it is feasible to design RNA switches with prescribed structural alternatives. We discuss the theoretical background and present an efficient tool that allows the design of various types of switches. We argue that both the general proper ties of the sequence structure map of RNA secondary structures and the ease with which our design tool finds bistable RNAs strongly indicates that RNA switches are easily accessible in evolution. Thus conformational switches are yet another function for which RNA can be employed.