Robustness and modularity properties of a non-covalent DNA catalytic reaction

The biophysics of nucleic acid hybridization and strand displacement have been used for the rational design of a number of nanoscale structures and functions. Recently, molecular amplification methods have been developed in the form of non-covalent DNA catalytic reactions, in which single-stranded DNA (ssDNA) molecules catalyze the release of ssDNA product molecules from multi-stranded complexes. Here, we characterize the robustness and specificity of one such strand displacement-based catalytic reaction. We show that the designed reaction is simultaneously sensitive to sequence mutations in the catalyst and robust to a variety of impurities and molecular noise. These properties facilitate the incorporation of strand displacement-based DNA components in synthetic chemical and biological reaction networks

DNA nanomachines.

We are learning to build synthetic molecular machinery from DNA. This research is inspired by biological systems in which individual molecules act, singly and in concert, as specialized machines: our ambition is to create new technologies to perform tasks that are currently beyond our reach. DNA nanomachines are made by self-assembly, using techniques that rely on the sequence-specific interactions that bind complementary oligonucleotides together in a double helix. They can be activated by interactions with specific signalling molecules or by changes in their environment. Devices that change state in response to an external trigger might be used for molecular sensing, intelligent drug delivery or programmable chemical synthesis. Biological molecular motors that carry cargoes within cells have inspired the construction of rudimentary DNA walkers that run along self-assembled tracks. It has even proved possible to create DNA motors that move autonomously, obtaining energy by catalysing the reaction of DNA or RNA fuels

Design and assembly of double-crossover linear arrays of micrometre length using rolling circle replication

We demonstrate the use of rolling circle replication to template linear DNA arrays whose sizes bridge the gap between nanometre-scale self-assembly and top-down lithographic fabrication. Using rolling circle replication we have produced an oligonucleotide containing several hundred repeats of a short sequence motif. On this template we have constructed, by self-assembly, an array consisting of two parallel duplexes periodically linked by antiparallel Holliday junctions. We have observed arrays up to 10 νm in length by atomic force microscopy. © 2005 IOP Publishing Ltd

Kinetically controlled self-assembly of DNA oligomers.

Metastable two-stranded DNA loops can be assembled into extended DNA oligomers by kinetically controlled self-assembly. Along the designed reaction pathway, the sequence of hybridization reactions is controlled by progressively revealing toeholds required to initiate strand-displacement reactions. The product length depends inversely on seed concentration and ranges from a few hundred to several thousand base-pairs

Templated self-assembly of wedge-shaped DNA arrays

We demonstrate the use of a one-dimensional template to control the shape of a two-dimensional array self-assembled from a minimal set of DNA tiles. A periodic single-stranded template seeds tile assembly. A unique vertex tile at the 5′ end of the template controls the positioning of edge and body tiles to create a wedge-shaped array. The vertex angle of the array is approximately 12°; edge lengths are of the order of 1 μm. © 2008 Elsevier Ltd. All rights reserved

Interleukin-6 enhances expression of adenosine A(1) receptor mRNA and signaling in cultured rat cortical astrocytes and brain slices

The inhibitory neuromodulator adenosine is released in the brain in high concentrations under conditions of exaggerated neuronal activity such as ischemia and seizures, or electroconvulsive treatment. By inhibiting neural overactivity, adenosine counteracts seizure activity and promotes neuronal survival. Since stimulation of adenosine A(2b) receptors on astrocytes induces increased synthesis and release of interleukin-6, which also exerts neuroprotective effects, we hypothesized that the effects of interleukin-6 and of adenosine might be related. We report here that stimulation with interleukin-6 of cultured astrocytes, of cultured organotypic brain slices iom newborn rat cortex, and of freshly prepared brain slices from rat cortex induces a concentration- and time-dependent upregulation of adenosine A(1) receptor mRNA. This increased adenosine A(1) receptor mRNA expression is accompanied in astrocytes by an increase in adenosine A(1) receptor-mediated signaling via the phosphoinositide-dependent pathway. Since upregulation fo adenosine A(1) receptors leads to increased neuroprotective effects of adenosine, we suggest that the neuroprotective actions of interleukin-6 and adenosine are related and might be mediated at least in part through upregulation of adenosine A(1) receptors. These results may be of relevance for a better understanding of neuroprotection in brain damage but also point to a potential impact of neuroprotection in the mechanisms of the antidepressive effects of chronic carbamazepine, electroconvulsive therapy, and sleep deprivation, which are all accompanied by adenosine A(1) receptor upregulation. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. All rights reserved