Using aspirin to study bacterial infection
Nature Methods
A method published online this week in Nature Methods using aspirin to turn on expression of a bacterial gene inside an infected host provides an easy and safe way to study host-pathogen interactions.
Bacteria express a range of different genes when they infect a host organism. These genes are expressed at different times and have distinct effects on the virulence of the microorganism. Studying this process has been hampered by a lack of methods to selectively modulate the expression of bacterially expressed genes in a tightly controlled and safe way in the whole animal.
Eduardo Santero and colleagues describe how a gene expression control circuit that responds to acetyl salicylic acid (aspirin) can be incorporated into bacteria and used to control the expression of a specific gene. As a proof-of-principle they validated their method by engineering salmonella to express an enzyme that converts an innocuous chemical to a cytotoxic compound. By infecting mice with the engineered salmonella they showed that aspirin administration was able to turn on expression of the inserted gene in salmonella infected cells and kill them.
This proof-of-concept demonstration indicates that the method should be broadly applicable to the study of physiologically relevant host-pathogen interactions if it is used to control natural or engineered bacterial genes.
CONTACT
Eduardo Santero (Universidad Pablo de Olavide, 41013 Sevilla, Spain)
Tel: +34 954349160; E-mail: esansan@upo.es
Cost effective individual genome sequencing
Nature Methods
This week Nature Methods presents three reports that introduce different techniques for selecting and enriching specific genomic regions in a high-throughput fashion. These methods will pave the way for cost-effective sequencing of individual human genomes, enabling large numbers of genomic regions to be extracted from a sample before sequencing and thus allowing researchers to sequence only the genomic regions of interest.
To capture in a single reaction close to 10,000 exons—the protein encoding parts of genes—Jay Shendure and George Church made probes identical to short-sequence stretches in the exons and used them as baits to fish out their targets. After amplification, they sequenced the captured targets with high-throughput technology.
In a complementary approach two independent groups, one led by Tom Albert and Richard Gibbs, the other by Michael Zwick, use hybridization to DNA microarrays to enrich their samples in sequences of interest. The sequences from a genome sample that are captured on the microarray can then be released and sequenced.
CONTACT
Jay Shendure (University of Washington, Seattle, WA, USA)
Tel: +1 206 685 8543; E-mail: shendure@u.washington.edu
Tom Albert (NimbleGen Systems Inc, Madison, WI, USA)
Tel: +1 608 218 7613; E-mail: talbert@nimblegen.com
Richard Gibbs (Human Genome Sequencing Center, Houston,
TX, USA)
E-mail: agibbs@bcm.tmc.edu
Michael Zwick (Emory University School of Medicine,
Atlanta, GA, USA)
Tel: +1 404 727 9924; E-mail: mzwick@genetics.emory.edu
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