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Blocking gene expression by interfering with translation of mRNA can be accomplished by means of antisense or short interfering RNA strategies, but more potent inhibitors would act by inhibiting transcription of genomic DNA. Two new studies show efficient inhibition of transcription using single-stranded peptide nucleic acid or double-stranded RNA targeted to the open complex formed at the transcription start site.

Examples abound in nature in which organisms adapt and optimize their fitness in a given environment. A new study demonstrates that a cellular cost-benefit analysis drives growth optimization over the course of evolution by attenuation of protein expression levels.

Voltage-gated ion channels respond to alterations in membrane potential and mediate action potential in neurons. A recent study provides new insights into the structure and gating of the Shaker potassium channel.

Iron-sulfur clusters and hemes are two iron-containing prosthetic groups involved in important physiological functions. Identification of the gene responsible for anemia in a mutant zebrafish has revealed an unexpected link between iron-sulfur cluster assembly and heme synthesis in red blood cells.

Near-field scanning optical microscopy has been used to study the organization of β₁- and β₂-adrenergic receptors in cardiac cells. The fluorescently labeled receptors organize into distinct clusters, which may represent localization in microdomains such as lipid rafts and caveolae.

Activity-based probes can be used for monitoring enzyme activity based on their covalent reactions with active-site residues. A quenched activity-based probe has now been developed that becomes fluorescent only after labeling active proteases. The specificity of the fluorescent signal and cell permeability of the small molecule make this probe effective for monitoring protease activity in living cells.

The growth of research at the chemistry-biology interface provides a unique opportunity to inspire undergraduate students to pursue careers in science and to educate science and nonscience students broadly in both chemical and biological sciences.

Chemical genomic approaches offer an alternative to traditional high-throughput screening for drug discovery and provide an emerging approach to probing cellular biology. The 58^th Ernst Schering Foundation Workshop on “Chemical Genomics: Small Molecule Probes to Study Cellular Function,” held April 6–8, 2005, in Berlin, Germany, captured recent chemical genomics advances and highlighted the power of a tight integration of chemistry and biology.

Chemical biologists studying natural-product pathways encoded in genomes have unearthed new chemistry and insights into the evolution of biologically active metabolites.

Protein nitrosation is an important signaling mechanism in vivo; however, mechanisms for selective nitric oxide modification of cysteines have not been described. Thioredoxin is now shown to rapidly and site-specifically catalyze S-nitrosation of an active site cysteine of caspase-3.

The identification of promising lead compounds from high-throughput screens is still a very complex problem. A new high-throughput assay for identifying aggregation-based false positives could help.

In the competition for control of iron between Mycobacterium tuberculosis and host cells, very little is understood about how these bacteria use small-molecule siderophores to obtain iron. A mechanism is now shown for intracellular iron acquisition by mycobacterial lipophilic siderophores.