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"The combination of practical medicine and research will promote health in the best way"

Says Raizi - Geruda Sussman, winner of the UNESCO-L'Oréal Prize for Women in Science, student of medicine at Ben-Gurion University and biology student at the Hebrew University, preparing for a double doctorate, researching genetic diseases she encountered in the field

Raisi Groda-Sussman. Photography: Lem Welitz Studio
Raisi Groda-Sussman. Photography: Lem Welitz Studio

As part of the UNESCO-L'Oréal Prize for Women in Science ceremony, a special prize was awarded this year to student Raizi Groda-Sussman from the Hebrew University, for her research dealing with understanding the function of natural killer cells in immunodeficiency diseases with a genetic background.

In a conversation with the science website, Groda-Sussman explains: "The laboratory I am in studies cells of the immune system called natural killer cells and the role of these cells is to kill cells that are infected with a virus or cells that have undergone a cancerous transformation."

Usually when you want to investigate the function of a protein in biology, you disable the gene in a mouse and see what effect the protein deficiency has on the mouse, but you have to remember that the mouse does not always simulate the real situation in humans. Nature sometimes provides us with the possibility to study the function of a certain protein in a person, in the form of genetic diseases in which there are patients in whom a certain protein does not function or is missing. When we study the disease in these patients we also promote the basic knowledge of mechanisms in the body and try to find a medical solution for the patients.

"My idea is to connect medicine and basic research and I implement this through a biological study of patients with two genetic diseases. These are two families that each had children with a different rare genetic disease. The first family is an Israeli Arab family who have three children with a rare disease of which only 11 patients are known in the whole world - BLS1. In this disease there is a deficiency in a protein whose function is to cause proteins called MHC - tissue matching molecules - to be presented on the surface of the cell. These proteins are displayed on the surface of the cell and look like a small bowl. Inside the bowl is displayed content from the contents of the cell. The content can be the content of a healthy cell, the content of a virus that has infected the cell, or alternatively, cancerous content if the presenting cell has undergone a cancerous transformation. In the immune system there are T-type cells whose role is to check the contents of these bowls and in the event that the displayed content originates from a bacterium or the T-cell virus will lead to the elimination of the cell. In order to evade the T-cells, they developed
The viruses have evasion mechanisms in which they prevent the expression of the MHC proteins on the surface of the cells and thus they "hide" from the T cells of the immune system. But the immune system is more complex and this is where the natural killer cells of the immune system play a role. The natural killer cells distinguish between a cell presenting the MHC molecule (the body's own cell) and a cell that does not present the MHC molecule (a foreign cell or a cell trying to hide a virus). When such a killer cell does not recognize the presence of MHC it destroys the cell.
Patients with BLS1 disease do not have the MHC proteins and therefore nothing is displayed on their cell surface. This means that the immune system cells do not actually recognize anything. Can't tell if there is infection or not. And so these patients constantly suffer from recurrent infections.
And here we come to the question - if the body cells in the patients do not present MHC molecules, why don't the killer cells eliminate all the cells in these patients? Why don't the patients suffer from autoimmune diseases in which the killer cells eliminate the patients' cells?

"In recent years, there have been theories that say that in order for the killer cells to kill, they must go through a process of education in which they essentially receive a "license to kill" and as learned from mice, the MHC molecules are the ones that give the license to kill during the development of the killer cells. As it turns out from the study in this family of patients, the killer cells in these patients do not receive a license to kill because they are not exposed to the MHC molecules during their development and therefore they fail to kill the patients' own cells. This is probably the least bad because although the patients suffer from many infections, on the other hand they are not eliminated by their killer cells.

"We also found the mutation that causes this disease and it may not be so important to us in terms of biological knowledge, but it is important to the family, the eldest daughter got married not long ago and this allows her to do a type of genetic review to check her husband and make sure he is not a carrier of the gene and to enable better family planning .”

The second family is a Palestinian family whose two-year-old daughter is being treated in Israel after her two brothers died at a young age. It turns out that this is a disease that was identified in recent years and is called LAD3, and in which a protein called kindlin is defective which is apparently responsible for activating another protein called integrin. Integrin has different roles in different cells and, among other things, it is involved in the formation of blood clots, it has a role in recruiting the cells of the immune system from the blood to the area of ​​inflammation. And it also has a role in creating the connection between the killing cells and the cell that is about to be eliminated (we talked about them in the first disease). The girl who suffers from a deficiency in the function of the kindlin protein, suffers from many bleedings and infections. Since this is a new disease, it is not clear what exactly is happening there and how the kindlin activates the integrin. We are checking what is happening in the killer cells in terms of this disease and trying to understand what the kkindlin is doing - this research is in collaboration with Weizmann and Imperial College in London."

In conclusion, Groda-Sussman says that the research begins with a question that appears in the clinic, moves to basic biology and returns to the clinic, where the results are used to develop a treatment or locate the mutation that allows for improved diagnosis and suggested treatments.

She will soon finish her research as part of her doctoral thesis (PHD) in Jerusalem and return to medical studies in Ben Gurion. "I still have a long way to go, because I will have to do an internship and an internship and I hope to integrate the research again in the internship phase. I think the combination is essential and necessary because studying human-related biology without understanding the clinical implications is not good enough. And also for medicine - if you have a more creative way of thinking and you don't take things as a grocery list for granted, everything complements each other very nicely."

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