test tube science 88.
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Researchers at the Technion-Israel Institute of Technology in Haifa have for the first time decoded the mechanism in which fusion occurs between cells.
The ability of two cells to fuse into a single large cell is essential to the initial creation of the embryo - the fusion of the sperm and the egg - and in the development of such body cells as bone, muscles and placenta. In addition, fusion between cells is the determinant in infection of body cells by viruses.
Professor Benjamin Podbilewicz of the Technion's biology faculty, together with his team from Haifa and from the US National Institute of Child Health and Human Development, published their findings in the latest edition of the prestigious scientific journal Developmental Cell.
Lately, the importance of fusion processes in the development of stem cells, and in prevention of the development of cancerous growths, has become increasingly clear. Despite the tremendous importance of this process, the genes involved remained unknown.
Understanding the fusion mechanism has many implications for medicine, including the development of the ability to cure sick tissue and organs by fusing them with healthy stem cells, and new ways to limit development of cancerous growths by preventing cancerous cell fusion.
In the distant future, it may be possible to decode the mechanism by which the sperm and the egg fuse, thereby providing a solution to the problems of infertile couples.
The researchers worked on a type of tiny nematode worm often used as a research model, the C. elegans. In 2002, the Technion researchers - in cooperation with two American groups - discovered the EFF-1 gene, which is essential to the fusion process. In 2004, they succeeded in proving that this gene is sufficient to create fusion and can by itself initiate the process. Now, they have found the way in which this is accomplished.
The fusion mechanism of the EFF-1 protein was explored, in cooperation with a US researcher in the laboratory of Dr. Leonid Chernomordik, who specializes in researching membrane fusion reactions used by viruses, such as influenza virus, to infect cells.
Using insect cells, the researchers succeeded - for the first time - in fusing cells outside the body in a Petri dish. They achieved this by inserting the EFF-1 gene of the C. elegans into insect cells. Thus, they showed that fusion between cells can be caused by the activities of the EFF-1 protein without the need for other proteins. They then examined whether the mechanism of cell fusion by the EFF-1 protein is similar to that observed in viruses, in spite of the fact that they involve different fusion proteins.
"It is clear to us that the same mechanism is at work in both cases. The cell envelope has two layers - an outer and an inner", Podbilewicz explained.
"Cell fusion is first carried out in the outer layer and afterwards in the inner one. This creates a two-way channel through which the contents move from cell to cell. Nevertheless, there is also a difference between the mechanisms: While the virus fusion with the target cells is a one-way process in which the fusion-inducing gene is found only in the virus and does not exist in the target cell, cell fusion by EFF-1 is a two-way process; hence the need for the presence of EFF-1 in both the merging cells."