MRC Laboratory of Molecular Biology, Cambridge

A molecular biologist gets excited about making designer proteins in cells.

The genetic code describes the relationship between the heritable information in the genome and the amino acids that are strung together to make proteins. This code, like any that contains redundancy, is open to hacking, and I have long been fascinated by how the process of translation, by which cells string amino acids together, might be reprogrammed to make new polymers. Several labs have already manipulated cells to incorporate designer amino acids into their proteins.

But Peter Schultz and his colleagues at the Scripps Research Institute in La Jolla, California, have achieved something remarkable. Proteins are made from a set of 20 amino acids, each of which contains an amine and a carboxylic acid group flanking a central carbon atom. Schultz's team engineered a bacterial cell to work with amino-acid-like molecules called -hydroxy acids that have an alcohol group where the amine would normally be. During translation, instead of forming an amide bond to link polymer subunits, this -hydroxy acid forms an ester bond (J. Guo et al. Angew. Chem. 120, 734–737; 2008).

Replacing a nitrogen and a hydrogen atom in a polymer chain with an oxygen atom might seem like a slight change, but it means that a protein can now be specifically cut at the ester bond in basic solution. Making esters from -hydroxy acids may first have been achieved with ribosomes in a test tube in the 1970s, but turning the process into a heritable, genetic property is a major advance: it takes synthetic biologists closer to creating organisms with designer codes to make new polymers.

One day soon, the creativity and skill with which chemists can make molecules will be coupled to the selective power of organismal evolution. And we will watch new life forms boot up.

Posted by Maxine Clarke at 08:59 AM | Permalink | Comments (0) | TrackBacks (0)

Imperial College, London.

A crystallographer takes a jaunt into immunology.

Although I spend most of my time exploring a landscape formed by atoms and bonds, I know it is healthy to make occasional journeys into less familiar territories, and I was intrigued to spot a paper on the curious interplay between infection and immunity in cattle with foot-and-mouth disease virus (FMDV).

FMDV, a highly contagious pathogen that can cause lameness, low weight and decreased milk production, is a scourge of agricultural livestock around the world. Although the acute phase of infection is rarely fatal, infection may persist in animals that have apparently recovered, creating a viral reservoir that some fear could contribute to the spread of disease. Nicholas Juleff and colleagues, from the United Kingdom's Institute for Animal Health, report a fascinating discovery that may have unlocked the secret of FMDV persistence.

They used an array of molecular techniques to search for traces of virus in tissues from the mouths and throats of infected cattle (N. Juleff et al. PLoS ONE 3, e3434; 2008). In a carefully controlled study, they found evidence of intact, non-replicating virus particles trapped by immune cells called follicular dendritic cells within the germinal centres of lymph nodes. Strikingly, virus was present for at least 38 days post infection, even though it was undetectable in surrounding tissues.

The retention of intact virus within germinal centres is likely to have a role in stimulating the long-lasting immune response of white blood cells that is characteristic of viral infections (but not current vaccine preparations) and echoes a pattern previously seen for HIV infection. The authors suggest that this capture may inadvertently also be responsible for preserving intact viruses capable of infecting susceptible cells as they come into contact with germinal centres. A causal relationship has yet to be firmly established but the paper illuminates a clear pathway by which to check this out.

Posted by Maxine Clarke at 08:53 AM | Permalink | Comments (0) | TrackBacks (0)