Its purpose is to catalog the immune peptide fingerprint of human cells and use these fingerprints to identify diseases
In recent years, the most difficult and important phase in the human genome project is coming to an end. In the process, a vast molecular knowledge was created that includes the genetic information of humans, the main of which is the determination of the nucleotide sequences of many people. This knowledge has already been translated into various research and medical uses and it is possible to discover the amino acid sequences of all the different types of human proteins.
Recently, with the human genome project reaching maturity, scientists are asking themselves "what next?" It is clear that determining the sequences of the different genomes is not the end of the process. There is still only partial knowledge about which of the various genes are indeed used to create the proteins in the various cells in the body's tissues. It is necessary to determine the amount of proteins in the various cells and tissues, and continue to discover which proteins participate in the various life processes, and how their three-dimensional structure enables their various functions. A lot of effort is also spent on clarifying what changes the cell proteins go through after they are created, what causes them to break down, and how long they stay in the cells until they are broken down. Of course, this broad knowledge is especially important for understanding the mechanisms of cell function, especially how the various proteins function when the cells become cancerous or infected with infectious disease agents, such as viruses and bacteria. Understanding the relationship between the structure and function of the various cell proteins makes it possible to develop new drugs for the various diseases and to create more effective vaccines to prevent them.
One of the areas of research that have been particularly successful from the Human Genome Project deals with the development of advanced methods for the early detection of diseases and the personalization of treatment, especially in cancer. Indeed, in the last year the Technion researchers succeeded in developing an innovative method that will be used in the future to diagnose diseases, based on a simple blood test. This advanced method could not have been created without the extensive knowledge gained, in part, by the Human Genome Project. The description of the innovative method was reported in an important international journal PNAS, which is the journal of the American Academy of Sciences. The method was developed in the laboratory of Professor Aryeh Edmon from the Faculty of Biology at the Technion, by Dr. Michal Basni-Sternberg as part of her doctoral thesis. As a follow-up to this important discovery, Professor Edmon and Dr. Basni-Sternberg propose in an article recently published in the prestigious scientific journal Molecular and Cellular Proteomics to develop a new research direction that will be based on the latest discoveries, and on the many technological advances, and will be the heart of an international project that will lead to an even deeper understanding of The human body and will enable the development of more effective vaccines for various diseases, including infectious diseases, cancer, and autoimmune and inflammatory diseases.
The new method for diagnosing diseases and the new project proposed by Professor Admon are based on the fact that all body cells (except red blood cells) of humans display a wide variety of different peptides on their surface that are used to inform the immune system about their health status. It is very important for the immune system of all animals to know at every moment about the state of health of the various cells, in order to prevent the spread of diseases in the body when the cells become infected with some disease agent that multiplies within them. The main tool with which the immune system learns about the invasion of pathogens, such as viruses and bacteria, into the cells is based on the presentation of peptides on the surface of the cells with the help of the HLA protein (Human Leukocyte Antigen - tissue compatibility complex). These peptides, built from segments of eight to eleven amino acids, are formed inside the cells as a result of the breakdown of the various cell proteins. Normally, cell proteins break down after they have exhausted their cellular function or if there have been malfunctions in the process of their creation and they were mistakenly created as defective proteins. These peptides are sent by the cells to their faces, and thus they update the immune system which proteins were formed in the cells and broken down inside the cells. As long as the cells are healthy, the proteins they produce and break down are also normal proteins, and the immune system does not need to act. But when the cells become infected with any disease agent, such as a virus or bacteria that has penetrated them, or when they go wrong and become cancer cells, they begin to create proteins inside them that are not produced in healthy cells. When these viral or cancerous proteins break down, the peptides, their breakdown products, are sent by the tissue adaptation complex protein to the surface of the diseased cells, where they are displayed "and inform" the immune system about the disease state. The cells of the immune system, called T lymphocytes, know how to recognize the fact that peptides derived from proteins related to the cause of the disease are displayed on the diseased cells. The T cells in response kill the infected cells, and at the same time alert the immune system to wake up and act more aggressively towards the cause of the disease.
In recent years, new methods have been developed and sophisticated devices have been invented that allow the identification and determination of the amount of proteins found inside the cells and with the same methods to also identify and determine the amount of peptides presented by the tissue adaptation complex on the surface of the cells. These developments allow the identification of thousands of peptides, and by comparing sick and healthy cells it is possible to identify the peptides that appear only, or mainly, in cells infected with viral diseases or peptides that appear in different types of cancer. The discovery of these peptides enables the development of immunotherapy for infectious diseases and cancer. Also, broad knowledge about the variety of these peptides can be used as a rich source of information about the biochemical processes that take place inside the cells and their state of health, which is why it is of the greatest research and medical importance.
The researchers suggest that the time is indeed ripe for the establishment of a new international project, which will be called the Human Immunopeptidome Project, and it will focus on the identification of all the peptides presented by the tissue adaptation complex in the different cells of the different tissues in humans in patients and in health, and according to the different subtypes of this protein in the human population. Over three thousand alleles of the tissue adaptation complex proteins are currently known, and each of these subtypes can display a variety of thousands of different peptides. Therefore, the variation of the peptides displayed on the surface of the various cells of humans is very great, probably reaching millions. Indeed, the technological development in the field of mass spectrometry allows the identification of tens of thousands of different peptides displayed on different types of cells.
The proposed project is particularly ambitious and can only be carried out with broad international cooperation. Its cost is high and of course it will take many years until its completion, but it is clear that the possible benefit from such a project is enormous and its contribution to medicine is immediate. If the human immunopeptidum project is indeed launched and the knowledge obtained during it will indeed be available to the entire scientific and healing community in the world via the Internet, the various researchers in the world will be able to use the knowledge and develop immune treatments for many diseases, and not only for infectious diseases, but also for the various types of cancer and many autoimmune diseases resulting from malfunctions that cause activity Excess of the immune campaign.
