Volume 1 Issue 4, September 2005

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.

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.

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.

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.

Cytochrome c release from the mitochondria is a critical component of the apoptotic cell-death program. Cytochrome c–catalyzed peroxidation of cardiolipin, a mitochondrial phospholipid, has now been shown to lessen the binding of cytochrome c to the mitochondrial inner membrane and facilitate permeabilization of the outer membrane. These results describe a new and earlier pro-apoptotic role for cytochrome c.

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.

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.

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.