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March 03, 2008

Key protein, FOX03a, helps shields some people from HIV, could lead to HIV vaccine

. In an advance online edition of Nature Medicine, the scientists explain how the protein, FOX03a, shields against viral attacks and how the discovery will help in the development of a HIV vaccine. This research could also advance therapies for other viral diseases.

Given their perfect resistance to HIV infection, elite controllers represent the ideal study group to examine how proteins are responsible for the maintenance of an immune system with good anti-viral memory," said Dr. Haddad. "This is the first study to examine, in people rather than animals, what shields the body's immune system from infection and to pinpoint the fundamental role of FOX03a in defending the body."

Beyond HIV treatment, Dr. Sékaly said his team's discovery offers promise for other immune diseases. "The discovery of FOX03a will enable scientists to develop appropriate therapies for other viral diseases that weaken the immune system," he said, citing cancer, rheumatoid arthritis, hepatitis C, as well as organ or bone marrow transplant rejection.


In separate but related news, Rockefeller University researchers have built a device that, by allowing scientists to turn genes on and off in actively multiplying budding yeast cells, will help them figure out more precisely than before how genes and proteins interact with one another and how these interactions drive cellular functions.


Although scientists have had the tools to track single cells and measure the protein levels within them, the new device allows scientists to track them for a longer period of time while not only monitoring but also controlling the activity of genes. The precision with which the device can track single cells also allows scientists to construct pedigrees, making it possible to compare gene activity from one cell to the next.

The device relies on electrovalves to control a flow of media, which travels through a tube and then diffuses across a porous membrane to reach the budding yeast cells. The cells are clamped between this membrane and a soft material, which forces them to bud horizontally without damage.

“That was the major design hurdle,” says Charvin. “To create a device in which cells don’t move, so that you can track hundreds of single cells for a long time — about eight rounds of cell division — which typically lasts 12 hours.”

In order to induce the activity of a gene, the researchers used inducer molecules that diffuse through the cell membrane and control DNA segments called promoters. The molecule’s presence silences the promoter, which silences the expression of the gene; the molecule’s absence, on the other hand, activates the promoter, which activates the gene to crank up the molecule’s production.

By exploiting this principle, the scientists showed that they could successfully turn specific genes on and off by controlling the flow of an inducer molecule called methionine. They observed that pulses as short as 10 minutes led to changes in protein levels that could be measured.

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