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Researchers at the Weizmann Institute have developed a method for studying proteins in a single cell extracted from a living body - without the need for artificial growth of cells outside the body

Cellular "selfie": an mTEC cell that was photographed using the new method called PLIC. The green dots indicate an interaction between proteins that helps prevent an autoimmune attack. Source: Weizmann Institute magazine.
Cellular "selfie": an mTEC cell that was photographed using the new method called PLIC. The green dots indicate an interaction between proteins that helps prevent an autoimmune attack. Source: Weizmann Institute magazine.

The technologies that exist today make it possible to know almost everything about the human genome from a sample of genetic material from a single cell. However, the next necessary step - the study of the proteins encoded by the genome - often requires collecting samples of millions of cells, an amount that is not available when it comes to rare cells found in the body in small quantities. In the study thatRecently published in the scientific journal Nature Communications. Introducing Dr Jacob Abramson and his group, in the Department of Immunology at the Weizmann Institute, a method for studying proteins in a single cell extracted from an animal or human body. To this end, the scientists used rare cells called mTECs, which function as a kind of genetic "selfie photos", because they present an almost complete picture of the genome: unlike other cells in the body, mTECs have the ability to express almost the entire protein-coding genome.

The mTEC cells are indeed a fraction of the cells of the thymus gland, a gland that serves as the main headquarters of the immune system, but without these cells, our body would simply destroy itself. Since these rare cells express almost the entire genome that encodes proteins, they produce a kind of "library" of all the body's proteins in order to teach the immune system not to attack these substances. Therefore, the mTEC cells can also kill or neutralize T cells that may act against the body's own tissues, thus preventing cases of "firing from the fire of our forces".

In order to investigate interactions between proteins within the mTEC cell, research student Ayelet Evin, postdoctoral researcher Dr. Ma'ain Levy, and Dr. Ziv Porat From the Department of Life Sciences Research Infrastructures, a new method called PLIC, which is a combination of two technologies: one marks changes in proteins or interactions between proteins using fluorescent detectors, and the other identifies the location of many fluorescent tags in a single cell. And so, this highly sensitive technology makes it possible to locate and quantify changes in proteins or interactions between proteins in a single cell, even when these proteins are present in minute amounts.

From the right: Dr. Ziv Porat, Dr. Yaakov Abramson, Dr. Maayan Levy and Ayelet Evin. Rare cells that function as a kind of "selfie photos". Source: Weizmann Institute magazine.
From the right: Dr. Ziv Porat, Dr. Yaakov Abramson, Dr. Maayan Levy and Ayelet Evin. Rare cells that function as a kind of "selfie photos". Source: Weizmann Institute magazine.

Using this method, the scientists were able to discover in detail - and for the first time in the natural environment of a cell isolated from the body - one of the mechanisms by which an mTEC cell prevents the immune system from launching an autoimmune attack. The scientists showed that the mTEC activity results from an interaction between two main proteins: one encoded by a gene called AIRE, and another encoded by a control gene called SIRT1. They also found that SIRT1 activates AIRE by removing an acetyl group chemical tag from it. In addition, the scientists showed, using the method, that AIRE proteins bind to each other and form active complexes - just as it emerged fromhis previous studies of Dr. Abramson.

According to Dr. Abramson, these insights may allow a better understanding of autoimmune diseases, as they can direct scientists to the genetic and mechanistic defects that cause these diseases. For example, the fact that SIRT1 is involved in the prevention of autoimmune attacks indicates that mutations or "different spelling" in this gene may contribute to the formation of several autoimmune diseases. The study may also help to understand how exactly mutations in the AIRE gene can cause autoimmune diseases. Dr. Abramson explains: "There are many advantages to being able to study interactions between proteins at the level of a single cell. In this way, rare cells can be studied as they are in the body, without the distortions that occur when many cells are artificially grown outside the body."

Institute scientists have shown that PLIC can be used not only in mTECs, but also in other cells. Therefore, apart from its contribution to the study of autoimmune diseases, the new method can contribute to the study of stem cells, rare cells in the inner lining of the intestines, or other types of cells found in the body in very small quantities.

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Although the mTEC cells represent less than 0.1% of thymus gland cells, they express the largest number of genes in our body - more than 90% of the protein-coding genome.

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