Reporting from the field

How to insert a reporter gene that tells about what is happening in the cells of a diseased organ, without the body breaking it down

From the right: Dr. Batia Cohen, Prof. Michal Naaman, Vicky Flex and Keren Ziv.

Biologists facing the need to receive real-time information about the events taking place in the molecular world use the services of "reporter genes", which transmit accurate data directly from the centers of intracellular events. A scientist interested in learning about the activity of a certain gene attaches to it, using the methods of genetic engineering, a reporter gene that follows it. Activation of the reporter gene produces an easily detectable protein. For example, GFP is one of the common reporter genes, because when it is expressed as a protein, it "announces" its presence through the green light it emits. This report allows scientists to receive reliable information about the places, times and intensity at which the gene is activated, the control mechanisms for its activation, etc.
However, due to the dispersion of the light in the tissues of the body, the ability to locate the focus from which the light is emitted is low. To solve the problem, researchers are trying to find reporter genes whose activity can be detected using magnetic resonance imaging (MRI) devices. However, all the genes that have been proposed so far as candidates for this role require the provision of additional material, which will allow the MRI device to detect the signal of the reported gene. These substances are unable to pass through various natural barriers in the body, thus preventing the access of the reporter genes to many important areas. Thus, for example, they cannot provide information about the development of the fetus (surrounded by the placental barrier), or about the central nervous system (located behind the blood-brain barrier).
Prof. Michal Naaman and Dr. Batia Cohen from the Department of Biological Control at the Weizmann Institute of Science, together with research students Vicky Flax and Keren Ziv, recently succeeded in creating genetically modified mice, which carry a promising new reporter gene, capable of overcoming these problems. The reporter gene, called ferritin, encodes a protein that plays an important role in the body: it captures iron from the cells and neutralizes it. Excess production of the ferritin protein, by methods of genetic engineering, increases the storage of iron in the cells. These changes can be seen through MRI, without the need to administer any additional external substance.
In a study whose results were published in the scientific journal Nature Medicine, the researchers showed that ferritin acts as an accurate, efficient and reliable reporter gene. His reports from the liver, from the endothelial cells (the cells that line the blood vessels) and from various stages during the development of mouse embryos, were well captured by the MRI device. Dr. Cohen: "This approach may help in studying the activity of various genes in developmental processes, and in monitoring migrating cells in the body. It will also be possible to use the method in researching models of various diseases, for example in the liver and brain, and in monitoring the development of tumors."