Directed evolution

The epidermal growth factor receptor 1 (EGFR) is overexpressed in various malignancies and is associated with a poor patient prognosis. A small, receptor-specific, high-affinity imaging agent would be a useful tool in diagnosing malignant tumors and in deciding upon treatment and assessing the response to treatment. We describe here the affinity maturation procedure for the generation of Affibody molecules binding

Development of artificial enzymes designed for industrial plants that could convert carbon dioxide into carbonates, with the ultimate aim of reducing CO2 emissions. Enzymes are biological catalysts that accelerate chemical reactions, such as the conversion of gaseous carbon dioxide (CO2) into carbonates. Carbonates are the basic component of coral reefs, mollusc shells, geological platforms and kidney stones. Although naturally occurring enzymes would be ideal for converting human-generated CO2 emissions into carbonates, they are generally incapable of coping with the extreme conditions of industrial plants. Ernesto and colleagues are now developing artificial enzymes that can withstand the harsh environments of industrial plants while accelerating chemical reactions. His team ultimately aims to create a clean, cheap, practical and socially responsible solution for global warming by reducing CO2 emissions. "We believe that our novel artificial enzymes will be the first tailor-made enzymes for industrial plants to produce carbonates," says Dr Hernandez. So far, Dr Hernandez and his colleagues have built an artificial environment composed of chimney-like equipment, measuring 1.5 metres in height and 15 centimetres in diameter, that mimics the smoke released by power plants. Using the artificial environment, the researchers will ensure that their artificial enzymes can function properly under extreme conditions consisting of hot, corrosive, poisonous and sticky smoke as well as soot and other gases produced by power plants. The team is basing the development of its artificial enzyme on naturally occurring carbonic anhydrase (CA), which accelerates the conversion of CO2 into carbonates. Carbonic anhydrase is capable of turning CO2 molecules into carbonates at a rate of one million molecules per second. However, "the enzyme's CO2 conversion rate slows down dramatically under industrial conditions," Dr Hernandez points out. He and his colleagues are now engineering artificial enzymes based on natural CA, using directed evolution techniques. Their first step involves the creation of a library of diverse genes that encode for carbonic anhydrases. "This library includes sequences of unique forms of carbonic anhydrases recently found near deep-ocean chimneys (hydrothermal vents)," says Dr Hernandez. The team plans to modify and multiply the genes encoding for carbonic anhydrases using a molecular technique called random mutagenesis. The researchers will then place the mutated genes in the artificial environment to see which ones are most effective at converting carbon dioxide into carbonates. The best mutations will then be put through the modification and multiplication processes again. The researchers will repeat the whole process until they have isolated a mutated gene encoding for recombinant carbonic anhydrase that can convert CO2 into carbonates under industrial conditions. With the help of artificial enzymes, CO2-converted carbonates could be used in everything from baking soda and chalk to Portland cement and lime manufacturing.

Many people underestimate the effect that unifying principles have on the study of biology. Unifying principles are used to provide simplifying assumptions to complex problems, which allow them to be effectively tackled by the tools at hand. However, erroneous unifying principles will generate simplifying assumptions that lead towards mischaracterizations of problems which inevitably lead to invalid conclusions. The unifying principles of the current Modern Synthesis of evolution are presently being challenged by the Extended Evolutionary Synthesis. However, the Extended Evolutionary Synthesis has so far failed to provide unifying principles of its own, which has caused many to question whether or not the Extended Evolutionary Synthesis is indeed a unique synthesis of evolutionary biology. Here, the concept of evolutionary teleonomy (Ernst Mayr's concept of teleonomy applied to evolutionary processes themselves) is identified as a unifying principle of the Extended Evolutionary Synthesis. Additionally, specific examples are provided where modern research has been led astray by the unifying principles of the Modern Synthesis which would have been corrected by applying the Extended Evolutionary Synthesis with the unifying principle of evolutionary teleonomy.

Recent studies on microbial cytochrome P450 enzymes have covered several new areas. Advances have been made in structure–function analysis and new non-enzymatic/electrochemical systems for the replacement of NAD (P) H in biocatalysis have been ...

On the basis of a bioinformatic approach, we suggest that in invertebrates many ligands interact with a single, ancestral and generalized receptor driving ligand evolution. In vertebrates, on the other hand, the occurrence of gene/genome duplications induced the shift to a ligand-directed evolution of receptors.

The bright ultraluminous X-ray source (ULX), M33 X-8, has been observed several times by XMM-Newton, providing us with a rare opportunity to 'flux bin' the spectral data and search for changes in the average X-ray spectrum with flux level. The aggregated X-ray spectra appear unlike standard sub-Eddington accretion state spectra which, alongside the lack of discernible variability at any energy, argues strongly against conventional two-component, sub-Eddington models. Although the lack of variability could be consistent with disc-dominated spectra, sub-Eddington disc models are not sufficiently broad to explain the observed spectra. Fits with a ˜ Eddington accretion rate slim disc model are acceptable, but the fits show that the temperature decreases with flux, contrary to expectations, and this is accompanied by the appearance of a harder tail to the spectrum. Applying a suitable two-component model reveals that the disc becomes cooler and less advection dominated as the X-ray flux increases, and this is allied to the emergence of an optically thick Comptonization medium. We present a scenario in which this is explained by the onset of a radiatively driven wind from the innermost regions of the accretion disc, as M33 X-8 exceeds the Eddington limit. Furthermore, we argue that the direct evolution of this spectrum with increasing luminosity (and hence radiation pressure) leads naturally to the two-component spectra seen in more luminous ULXs.

An image analysis-based method for high throughput screening of an α-amylase mutant library using chromogenic assays was developed. Assays were performed in microplates and high resolution images of the assay plates were read using the Virtual Microplate Reader (VMR) script to quantify the concentration of the chromogen. This method is fast and sensitive in quantifying 0.025–0.3 mg starch/ml as well as 0.05–0.75 mg glucose/ml. It was also an effective screening method for improved α-amylase activity with a coefficient of variance of 18%.