The Curie Institute, Paris, France.

An expert in chromosome organization considers yeast in a new light.

As somebody who studies how DNA is packaged so that it fits inside the nucleus, and how this protein parcelling adds to the information held in the sequence of DNA bases, my work has focused on frogs and mammals. Brewers’ yeast (Saccharomyces cerevisiae) is one of the simplest organisms with nuclei. It has proved useful to researchers like me when considering subtle influences on gene expression that are also found in higher organisms.

But we have not found a yeast ‘counterpart’ for some mechanisms, such as those that rely on RNA to regulate gene expression. One example is RNA interference, by which genes are ‘silenced’ through destruction of the messenger RNA molecules that would otherwise convey protein ‘recipes’ from the nucleus to the cytoplasm. But this does not rule out similar effects on gene expression by other means, as Françoise Stutz and her colleagues at the University of Geneva in Switzerland have found (J. Camblong et al. Cell 131, 706–717; 2007).

This team stumbled across silencing of a different sort when they left plates of yeast to divide for varying amounts of time. They found that older yeast cells expressed a gene called PHO84 less than did younger cells, and that as the amount of mRNA encoding the Pho84 protein decreased, the level of an antisense (or mirror-image) version of this mRNA increased. A series of experiments led them to propose a mechanistic model in which tuning the RNA degradation machinery stabilizes the antisense transcripts, promoting modifications of chromatin — the DNA–protein complexes that make up chromosomes — and, in turn, regulating gene expression.

No one yet knows how common this effect is in yeast, nor whether it occurs in more complex lifeforms; but this paper does serve as a lesson to revisit our assumptions.

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Tyndall Centre for Climate Change Research, NOC, Southampton, UK

An oceanographer sees potential in accelerating rock weathering to soak up carbon dioxide from the air.

With CO2 emissions increasing by more than 2% per year, rather than decreasing by the 3% or so needed to effectively mitigate climate change, I am not surprised that many scientists are seeking alternative solutions to simply cutting greenhouse-gas outputs.

Various geoengineering schemes have been proposed — such as fertilizing the oceans with iron, a limiting resource for planktonic algae that take CO2 from the atmosphere — but these are unlikely to sequester large amounts of carbon in the long-term and may have serious ecological side effects. The thermodynamics of enhancing geochemical weathering look feasible, but the reactions are too slow to be really practicable.

Geochemists and engineers at Harvard University in Massachusetts and Pennsylvania State University recently suggested a kinetically preferable idea. They propose using the electrolysis of sea water to produce sodium hydroxide and hydrochloric acid, in a variant of the well-known industrial 'chloralkali' process, (K. Z. House et al. Environ. Sci. Technol. 41, 8464–8470; doi:10.1021/es0701816 2007).

Sodium hydroxide could either be used to scrub CO2 directly from the air, producing sodium bicarbonate, which is neutral and could be discharged into the sea, or be pumped directly into the ocean, increasing sea water's alkalinity and so its ability to absorb CO2. The hydrochloric acid could be neutralized fairly easily, because it reacts rapidly with both carbonate and silicate rocks.

The scheme House et al. outline looks promising if it were operated using a solar or geothermal electricity source near a supply of basic rocks. A mid-ocean volcanic island would be good. And the environmental consequences of the scheme's discharges should be less severe than those of the ocean acidification that humans are already causing.

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Howard Hughes Medical Institute, Stanford University School of Medicine, California

A developmental biologist muses on the magic of the egg.

Many biologists, myself included, grew up watching frogs’ eggs hatch into tadpoles at the warm surfaces of summer ponds. The yearly cycle provided a leisurely period of thought about basic biology. But few of us guessed how central to current biological and financial interests the egg would become. These days, an enucleated egg’s ability to reprogram the nucleus of a somatic cell — first demonstrated in frogs’ eggs in 1958 — promises an era in which organs could be picked up like junkyard parts.

What magic does the egg possess that allows it to reset the nucleus to a basal, or ‘pluripotent’, state from which all cells can be generated? The three famous transcription factors — Oct4, Sox2 and Klf4 — that are required to transform a skin cell into a pluripotent cell provide some insight. But do these recapitulate a pattern used by the egg during development, or induce reprogramming by an alternative pathway?

John Gurdon and his colleagues at the Gurdon Institute in Cambridge, UK, have purified the proteins that bind to the regulatory sequences of the Oct4 gene in frogs’ eggs (M. J. Koziol et al. Curr. Biol. 17, 801–807; 2007). The group chose Oct4 because its regulatory regions have been clearly defined. They found that the initiation of Oct4 expression involved, in addition to likely candidates, some unexpected proteins.

If, as many scientists think is the case, the re-establishment of pluripotency involves shortcircuiting egg development, this suggests to me that the magic that allows the egg to reset a nucleus into a pluripotent state may lie in these unexpected proteins — as well as Oct4, Sox2 and Klf4. There is so much more to learn from watching frogs’ eggs grow up.

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Johns Hopkins University, Baltimore, Maryland

A geneticist wonders what it takes to prove causality.

In the post-genomic era, we are increasingly confronted by a torrent of variation data, originating from gene sequence, copy number and methylation patterns. To complicate matters further, I anticipate that a notable fraction of variation among individuals will be found to be relatively rare events. This would severely hamper our ability to implement statistical methods to associate variants with disease pathogenesis.

A recent paper by Carpten et al. (Nature 448, 439–445; 2007) highlights just how difficult solving this problem can be. The authors found a somatic missense mutation in AKT1 in a small number (2–6%) of breast, colon and ovarian cancers, and expended considerable effort establishing its link to tumour development. Experiments included solving the AKT1 protein's crystal structure; calculating the predicted effect of the missense change on the protein's conformation and binding abilities; gauging phosphorylation rates of the protein; identifying cellular localization; measuring transformational competency of the mutant versus wild-type allele; and checking the mutant protein's ability to induce cancer in a mouse model.

In light of recent efforts to understand the total mutational load in cancer (for some examples see F. Dahl et al. Proc. Natl Acad. Sci. USA 104, 9387–9392; 2007; C. Greenman et al. Nature 446, 153–158, 2007; T. Sjöblom et al. Science 314, 268–274; 2006), these data are both exciting and sobering, because the idea of performing such an exhaustive analysis on a large allelic series is not tenable. The challenge, therefore, is to solve this problem by developing functional assays that are physiologically relevant; amenable to at least medium throughput; and applicable to a range of mechanistic questions (not just neoplasia, for example).

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