University of Leicester, UK

A biochemist is excited by a universal glue for molecular biology.

Investigating the dynamic properties of proteins at the level of a single molecule allows insight into properties that are masked in ensemble studies. I have often found that the hardest part of such studies is immobilizing the molecule on a silica surface in a 'permanent' way that retains the molecule's function.

The proteins we investigate are usually prepared with a His-tag — comprising 6+ engineered histidine residues — that binds, via a chelated nickel ion, to nitriloacetic acid (NTA), aiding purification on an NTA affinity column. Immobilization through this tag would therefore be an attractive option. But alas, this is only partly successful using the standard NTA group because proteins have a significant probability of detaching from the silica support on the timescale of minutes.

But surely a chemist somewhere has improved on this technology? Thanks to Google, I found the work of Jacob Piehler who, in 2005, introduced tris-NTA, a cyclam ring with three groups attached to it. Tris-NTA shows a thousand-fold higher affinity for His-tags in the presence of nickel than NTA and a dissociation half-life of many hours.

Piehler and colleagues have gone on to exploit this technology as a general means of attaching fluorophores to His-tagged proteins and, most recently, as a convenient way of specifically conjugating proteins to streptavidin (A. Reichel et al. Anal. Chem. doi:10.1021/ac0714922; 2007).

The streptavidin-biotin complex is another widely-used 'glue' in biotechnology, but the use of an intermediate tris-NTA-biotin adaptor broadens its application to His-tagged proteins and renders the attachment reversible on addition of excess imidazole. I look forward to using this technology in our single-molecule studies, for which such a reversible glue has the same appeal as a Post-It note.

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Massachusetts Institute of Technology, Cambridge, USA

A biological engineer searches for simplicity.

Several years ago, a good colleague suggested that I read about a discussion held in 1864 on nuts and bolts (J. Franklin Inst. 77, 344–351; 1864). The focus was a paper by one William Sellers that argued for the adoption of a uniform system of screw threads — 60° angles, squared off along the edges.

Machinists across the United States eventually started producing nuts and bolts according to Sellers' scheme. As a result, hardware stores now offer a wide selection of standardized parts that can be used in combination and behave as expected.

Inspired by this example and others, I have been studying how synthetic biological parts might be made as regular and easy to use as Sellers' nuts and bolts.

The starting complexity of nature has led some distinguished researchers to doubt such work is practical. But given that there has been little research on manufactured bio-simplicity, this seems premature.

And there are examples: a team at the California Institute of Technology in Pasadena recently developed a uniform system for engineering simple biological switches made from ribonucleic acids (M. N. Win and C. D. Smolke Proc. Natl Acad. Sci. USA doi:10.1073/pnas.0703961104; 2007).

The 'nuts and bolts' of the switches are RNA sensor and actuator domains. The method for combining any sensor domain to an actuator domain through a third communication domain provides the 'uniform screw threads'. Because such switches are produced by a standard process, many switches could be quickly programmed to control diverse cellular functions in response to myriad molecular inputs, from small molecules, to peptides, to nucleic acids.

I suspect that further efforts to engineer biological simplicity will have similarly powerful results.

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Massachusetts Institute of Technology, USA

A bioengineer sees a future for safe gene-silencing therapies.

The possibility of treating genetic disorders by modifying gene expression has been an attractive yet elusive goal for decades. Problems with the safety and efficacy of various types of gene therapy have held back progress. In particular, there have been some high-profile failures, including a number of deaths during clinical trials.

But seminal studies reported by Andrew Fire and Craig Mello in 1998 led to a potentially new class of therapeutic agent. These researchers, who went on to share a Nobel prize for their work, found that small pieces of RNA, dubbed siRNAs, can silence genes.

Although switching off genes may have fewer complications than adding new ones, the safe and effective delivery of genetic agents remains a critical challenge. I was therefore pleased to see a recent paper reporting tests of an siRNA-delivery system in monkeys (J. Heidel et al. Proc. Natl Acad. Sci. USA 104, 5715–5721; 2007), suggesting that safe, repeated systemic administration of siRNAs is possible.

Mark Davis of the California Institute of Technology in Pasadena and his colleagues created nanoparticles composed of siRNAs and a novel polymer based on the sugar cyclodextrin. These particles were injected into the monkeys and their health was monitored. The monkeys tolerated multiple doses of siRNA of increasing amounts.

This paper was of interest to me not only because my group works on lipid formations that might serve as delivery systems for siRNA or other genetic agents, but also because I was pleased to see a former student doing well. Jeremy, the first author, once worked in my lab as an undergraduate.

Studies such as this one are bringing back to the field the excitement that surrounded gene therapies in the 1980s.

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Scripps Institution of Oceanography, La Jolla, California, USA

A marine biologist sees the potential of cyanobacteria, and the benefits of their renaming.

Let's start with a false syllogism: bacteria are prokaryotes, blue-green algae are prokaryotes, and therefore blue-green algae are bacteria. All other algae are eukaryotes and so, the argument went, we should reclassify the Cyanophyta as cyanobacteria.

I was never in favour of this renaming, but it may have been good for funding. I've heard that grant applications for research on bacteria have better chances of success than those for research on blue-green algae.

And these oft-neglected organisms have a lot to offer. A recent paper on Lyngbya majuscula from Bill Gerwick, now at the Scripps Institution of Oceanography in La Jolla, California, and his colleagues (B. Han et al. J. Nat. Prod. 69, 572–575; 2006), for example, reveals some interesting new compounds.

L. majuscula grows on warm seashores as tufts, which, when they come loose and float away, can stick to swimmers' skin and cause a rash — known as swimmers' itch or seaweed dermatitis.

Gerwick and his team extracted from dried L. majuscula two compounds that may explain its irritant effect. The compounds, aurilide B and aurilide C, are hugely complicated ring-shaped molecules that resemble a toxin previously isolated from sea slugs.

In tissue culture assays, the compounds proved toxic to human and mouse cancer cells. Such natural products can act as starting points for pharmaceutical chemists.

Gerwick's paper refers to L. majuscula as a cyanobacterium in its title and as an alga elswhere in its text, but what's important is the science, not the names.

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