Nature Biotechnology pp 460 - 466 and pp 445 - 446

A team of scientists from Norway has succeeded in coaxing one type of cultured adult cell to start behaving like a completely different type of adult cell. Their approach will aid scientists investigating the mechanisms by which adult stem cells revert to cells capable of differentiating into other types of cells of potential use in therapies for conditions like diabetes, Parkinson’s disease, and heart disease.

Traditionally, the differentiation of a cell from its embryonic form to a specialized adult form has been considered a one-way street. Once a stem cell has differentiated into a liver cell, for example, it doesn’t turn back into a primordial stem cell or change into some other kind of specialized adult cell, like a muscle cell or a blood cell. Recent work, however, has suggested this might not always be the case. Most spectacularly, the cloning of Dolly the sheep showed that a differentiated skin cell from an adult sheep can be reprogrammed by nuclear transfer into an egg so that it is capable of giving rise to all the cells of a new animal. Several researchers have also reported the presence of stem cells in adult tissues that are capable of turning into other completely different types of adult cells, but the capacity of such cells to differentiate into the >220 body cell types remains unknown.

Now, Phillipe Collas and colleagues report that cells derived from the skin (known as fibroblasts) can adopt many characteristics of a type of immune cell if they are incubated in extracts obtained from these immune cells. The fibroblasts will also become nerve-like after exposure to nerve cell extracts. While the reprogramming is impressive, it is incomplete. The reprogrammed cells do not become fully-fledged immune cells or neurons.

From a clinical perspective, approaches based on this technology might allow replacement cells to be generated that are compatible with a patient’s immune system, without the ethical problems of generating or destroying embryos.

Nature Biotechnology pp 478 - 483 and pp 445 - 446

David Pompliano and his colleagues describe a new way of screening for novel antibiotics that are likely to be more successful in the clinic than those identified using traditional high-throughput screening. Their approach may help in the race to find effective antibiotics with new mechanisms that can combat the rising incidence of bacteria resistant to conventional antibiotics. While high-throughput screening strategies have dramatically increased the number of candidate antibiotics identified by drug companies, these antibiotics often perform poorly in the clinic because they lack essential properties, such as an ability to penetrate bacterial cells. The assay described in this issue specifically identifies compounds that can penetrate bacteria and allows rapid identification of antibiotics that act on new bacterial gene targets.

To identify more efficacious compounds, the Pompliano and his team first engineered nine different strains of bacteria, each expressing a different essential gene at a low level, that grow much more slowly than the parent bacterial strain. Each of the strains was spotted onto an array so that each gene target was represented. The delicate growth of these "weakened" bacteria on the array compared with the parent strain, increased their sensitivity to candidate antibiotics. What’s more, knowledge of the essential gene affected in the strain targeted also implicated where the antibiotic was acting.

Screening nine strains from the array in parallel against a chemical library permitted identification of new inhibitors of bacterial growth. The strategy should allow assessment of which lead compounds have the best properties to determine which antibacterial targets are worthy of more intensive analysis.

Nature Biotechnology pp 473 - 477

A new approach called proximity ligation is capable of detecting the presence of a tiny number of molecules of a blood protein. Because it can directly detect proteins in human blood serum or cerebrospinal fluid and requires no tricky separation or washing steps, the method could one day prove useful in the clinic as an alternative to more common ELISA tests currently used to measure serum proteins.

Ulf Landegren and his colleagues set about to find an alternative to antibody-based tests, such as ELISA, by exploiting the exquisite recognition capacity of small DNA molecules (binders) for specific proteins. In their experiments, Landegren and his team chose a pair of DNA binders that attach to different sites on platelet-derived growth factor (PDGF), a blood protein commonly associated with inflammation. After addition of a third DNA molecule (connector), which joins the binders’ free ends in a manner similar to sticky tape, a conventional technique called PCR is then used to amplify the connector molecule to detectable levels.

The approach is around a thousand-fold more sensitive than a standard ELISA assay. The authors claim that they can detect vanishingly small amounts of PDGF in a sample—as few as 24,000 molecules.