Whitehead Institute for Biomedical Research, MIT, Boston

An immunologist marvels at dendritic cells.

Dendritic cells ingest and process all manner of bacteria and viruses, and display the invaders’ distinguishing structures so that other cells of the immune system ‘know’ what to ‘look for’. No adaptive immune response can begin without them. For years I have been fascinated by the internal details of dendritic cells that enable them to handle this task.

One set of details concerns how these cells manage protein production and disposal, given that breaking down and presenting sections of foreign proteins are the cells’ primary jobs. Last month, Hugues Lelouard and his colleagues at the University of the Mediterranean in Marseille, France, discovered that dendritic cells fine-tune the translation of messenger RNAs to proteins when they are activated by inflammatory stimuli (H. Lelouard et al. J. Cell Biol. 179, 1427–1439; 2007).

The authors’ stimuli of choice were lipopolysaccharides, signature molecules that indicate the presence of certain bacteria. Dendritic cells exposed to them showed a close correlation between the extent to which translation became more efficient and the increased formation of lumpy bodies similar to aggresomes, which is a prelude to the destruction of proteins. The authors then elucidated the biochemical steps that lead to enhanced translation of certain mRNAs when a dendritic cell becomes activated.

I consider it likely that the mRNAs in question are not randomly distributed throughout a dendritic cell’s cytoplasm. If this is so, these cells may contain a ‘translational hotspot’ of requisite proteins and enzymes around each pathogen containing vesicle, required for the orderly handling of the newly ingested microbe. The result might be the creation of an intracellular solid-state ‘device’ specifically for the processing and presentation of that microbe’s antigens.

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Howard Hughes Medical Institute, University of Pennsylvania, USA

A geneticist reflects on DNA sequence variants that influence gene expression and disease risk.

Most people are familiar with the Human Genome Project and the HapMap, which catalogued the millions of DNA-sequence differences among humans. But which of these differences influence our risk of developing diseases remains unclear. This is particularly true for disorders such as heart disease that involve not only many genes but also the interactions among them. In addition, the effects of variations in DNA sequence are often subtle, such as altered levels of gene expression. Identifying those DNA sequences that determine levels of expression across individuals could have great medical potential.

One paper that illustrates this point looks at the two major contractile proteins of the human heart, the - and -forms of the myosin heavy chain (E. van Rooij et al. Science 316, 575–579; 2007). Here, Eric Olson and his team at the University of Texas in Dallas identify a microRNA, called miR-208, that regulates how much of the -form heart cells produce.

A healthy heart requires a particular ratio of - and -heavy chains for its cells to function normally. When stressed, heart cells tend to make too much of the -form, causing the organ to enlarge, replete with fibrous connective tissue, and less able to contract. This often happens in people with heart disease.

In finding miR-208, the researchers have determined a key component in the molecular basis of heart failure. The next step might be to look for sequence variants of miR-208 and of other gene-expression regulators that could explain why some people are more susceptible to heart disease than others. In this way, whole biological networks could be pieced together and common medical problems more fully understood.

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Max-Planck Institute for Dynamics and Self-Organization, Göttingen, Germany

A physicist enthuses about criticality in biological development.

Physicists often overestimate the impact of their work on biological research. A biologist recently joked to me that physicists are rather like consultants: they appear without being asked and don't tell you anything new. As a physicist studying the spread of infectious diseases, I reckon there is some truth in this.

But biologists can underestimate our insights, too. The joke turned my mind to a paper by three physicists who applied the theory around spontaneous symmetry breaking to the development of body axes (J. Soriano et al. Phys. Rev. Lett. 97, 258102; 2006).

Spontaneous symmetry breaking occurs in, for example, a cooling magnetic material. At high temperatures, magnetic spins are randomly arranged, but as the material cools patches form in which the spins are aligned. At a critical temperature, the spins align throughout the material. A small, external magnetic field can then determine the system's fate, setting all the spins in a particular direction.

Soriano and his team studied symmetry breaking in developing hydra — multicellular organisms with clearly defined head and foot ends. Hydra can establish their body axis from a jumbled ball of cells, reminiscent of the way a magnetic material orders its spins as it cools. Patches of cells develop similar gene-expression profiles. This creates a system that is critically sensitive to tiny temperature gradients, which determine the direction of the body axis.

Impressively, Soriano and his team worked out the exponent in the size distribution of cell patches expressing a particular gene as a function of the age of the developing hydra. Through this, they related axis development to other self-organized critical systems physicists study, such as forest fires.

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