Nature Biotechnology pp 701 - 706

A way of studying the action of a breast-cancer drug in the body promises to facilitate the design of molecular-targeted therapies. The new method, described in the June issue of Nature Biotechnology, should allow scientists to determine the most effective strategies for administering this and other drugs to patients.

Drugs affect the behavior of molecules in the body, but the effects of drugs cannot readily be seen at the molecular level. The drug 17-AAG (currently in phase I clinical trials) induces the degradation of the protein HER2, a cell-surface receptor that plays a role in breast cancer. Smith-Jones and colleagues wished to understand the potency and time course of 17-AAG action on HER2. They attached a positron emitter to a fragment of Herceptin, an antibody that binds HER2, so that the antibody fragment could be detected repeatedly using PET imaging technology. After injecting the antibody fragment into mice and then treating the mice with 17-AAG, they could image the disappearance of HER2 over time.

In principle, the approach can be adapted to other drugs and molecular targets. It will be useful for understanding the action of drugs and for determining optimal doses and schedules.

Nature Biotechnology pp 732 - 738

Scientists have shown that it takes the combination of two types of fungus-fighting molecule to thwart a pathogen responsible for hundred of millions of dollars of crop damage each year. Fusarium head blight (FHB), or scab, is one of the most costly and damaging grain diseases in the world, threatening billions of acres of wheat, oat barley and rye each year. Now, in the June issue of Nature Biotechnology, researchers have found a way of battling blight fungus by hooking up three different antifungal proteins to an antibody fragment that binds the pathogen's cell wall. When they engineered thale cress (Arabidopsis) plants to produce these antifungal combos, plants were protected against blight fungus infection. The studies suggest that cereals engineered in a similar manner would also be more resistant to infection.

Using a common method to identify chicken antibody fragments that that effectively bind cell wall proteins from the blight fungus, the authors isolated an antibody fragment (CWP2) that was particularly effective at specifically binding the pathogen that did not bind other types of fungi. When the DNA sequences encoding CWP2 were joined to DNA sequences encoding three antifungal proteins, the authors demonstrated that the paired molecules were much more effective at stopping fungus growth than either CWP2 or antifungal protein alone. Thale cress plants expressing the antibody-antifungal protein combo were also remarkably resistant to blight fungus infection.

Nature Biotechnology pp 739 - 745

Scientists have created a plant that accumulates health-promoting essential polyunsaturated fatty acids by borrowing genes from algae and mushrooms. In the June issue of Nature Biotechnology, Baoxiu Qi and colleagues report the creation of a thale cress plant that can produce both omega-3 and omega-6 polyunsaturated fatty acids (PUFAs). Omega-3 PUFAs, such as EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), fulfill important roles in infant brain and eye development as well as protecting adults against hypertension, inflammatory disease and autoimmune disorders. Because omega-3 PUFAs are found primarily in cold-water fish and omega-6 PUFAs are limited to certain grains and poultry products, scientists have been striving to find good sources of these oils.

Now, Qi and his team have succeeded in creating such a plant by introducing into thale cress genes from two algae and one mushroom that encode enzymes enabling the production of a variety of omega-3 and 6 PUFAs. The accumulation of these fatty acids in plants represents a significant step in the search for alternative and sustainable sources of fish oils.