A collaboration between researchers from the Institute of Life Sciences at the Hebrew University and researchers from the Friedrich Meisher Institute for Biomedical Research in Basel, Switzerland, resulted in the discovery of the factor that can be used to prevent the formation of 14 rare genetic diseases
Collaboration between researchers from the Institute of Life Sciences at the Hebrew University and researchers from the Friedrich Miescher Institute for Biomedical Research in Basel, Switzerland, resulted in the discovery of the factor that can be used to prevent the formation of 14 rare genetic diseases. This factor is responsible for the correct location of specific genes in the cell nucleus.
According to Prof. Yossi Greenbaum from the Institute of Life Sciences in the Faculty of Natural Sciences at the Hebrew University, who headed the research group: "Until now it was known that the action of genes regulated specific proteins on the one hand and chemical changes on the other. Now another regulatory mechanism has been discovered, which places the genes precisely in the three-dimensional space of the cell nucleus. This mechanism has not yet been fully understood and most of the factors involved in it are unknown."
The researchers discovered that a central factor in determining the location of genes is a network of fibrous proteins (Lamin), and the absence of this network can lead to the formation of certain diseases. These fibrous proteins are mainly located on the periphery of the cell nucleus. The function of these fibers is to regulate the action of the genes, and the genes in turn encode the building blocks of the body. Mutations in the genes responsible for the action of the fibrous proteins will cause one of 14 rare genetic diseases in humans. Among them are diseases of premature aging as well as diseases of the heart, skin, bones and muscles.
During the experiment, which was done on a strain of tiny worm, the researchers manipulated and "turned off" the gene responsible for the action of the fibrous proteins. By doing this they were able to show that the fibrous proteins are necessary in the process of the three-dimensional positioning of parts of the DNA.
The researchers then injected the worm with a small amount of fibrous protein that carries a mutation that causes Amery-Dreyfus disease, a muscular dystrophy that can also cause heart defects. According to Prof. Yosef Greenbaum, "the mutation led to the formation of a non-standard array in the nucleus of the genes specifically responsible for the muscles, while the other genes were not affected. Worms with the mutation were characterized by an unusual muscle structure and poor muscle function - phenomena similar to those observed in humans suffering from Amery-Dreyfus."
One of the important conclusions of the study, published at the end of the week in the prestigious journal Current Biology, is that lamin protein fibers help organize "silent" genes in the nucleus, which enables the normal genes to function.
Another conclusion is that when a mutation associated with a certain disease is expressed in the action of a fibrous protein, it can dominantly disrupt the spatial organization of specific gene groups. For example those that control the muscles. This dominance and the relationship between it and muscle dysfunction characterize diseases such as Amery-Dreyfus.
The research was carried out by Prof. Yosef Greenbaum from the Silverman Institute of Life Sciences in the Faculty of Mathematics and Natural Sciences at the Hebrew University and his research students Anna Metut and Erin Baum, in collaboration with Prof. Susan Gasser and her students Breita Pike, Benjamin Tobin, Adrina Gonzalez and Peter Meister from the Institute on Name Friedrich Misher.
