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If we really want to know how to behave in our body work, we need to work in the field of disease. We may need to start going through the cellular "trash."
A group led by Yifat Merbl, from the Weizmann Institute of Science, developed a system that is "cellular dumpster-diving" with information about the cell that is not otherwise seen.
The group approached their new approach to profiling the immune cells of patients with an autoimmune disorder and discovered distinct evidence for a more advanced diagnosis of the causes of this disease and in the future, which may lead to better diagnostic techniques.
Some 70 percent of the proteins in the body are broken down by the cell's degradation and recycling known proteasomes. These are the short-lived proteins that are made for specific purposes, for example, to mount an immune response.
"These proteins can be produced in small amounts, relative to structural proteins, and can be tightly regulated and degraded quickly, so standard proteomics surveys tend to miss them," said Merbl. "But they are precisely the proteins that are crucial to the cell's functions, and thus their malfunctioning plays a role in many diseases. at successive snapshots of their house, where they can get some sense of their tastes , what medications they take, what they buy and where they traveled in the same way, when we looked at the contents of cellular trash cans, we were able to profile the disease state of the cell and its protein turnover, as well as uncovering some clues as to what goes wrong in these cells to bring about the symptoms of the disease. "
"We focus on degraded proteins, in general, because finding the proteins has been used in the major activities in the cell at that time," said Avital Eisenberg-Lerner in Merbl's lab. "For example, if it is used as a reference for the detection of such a disease, or if it is not safe to use it. The result may be cancer while degrading too much of an immune regulator or suppressor of inflammation may be badociated with autoimmune disease. "
The research team, which included the lab of Mariana Kaplan, a systemic autoimmune expert at the US National Institutes of Health, Nancy and Stephen Grand National Israel Center for Personalized Medicine on the Weizmann campus, focused on systemic lupus erythematosus (SLE) -an autoimmune disorder that is difficult to diagnose, which has no cure, and for which the cause remains unclear. Lupus is a cell-mediated complexion that is badociated with the body's own immune system.
Preserving proteins in the process of degradation
Crucial to the study is the technique developed for isolating the proteasomes from cells-pulling them together with the pieces of proteins, or peptides, stored in the midst of the degradation process or the proteasome machinery.
The team removed the proteasomes from white blood cells from both lupus patients and healthy controls, and then carefully pried the peptides out. These were screened with mbad spectrometry, and the discarded peptide profile of the two groups compared. The team named their approach MAPP, for Mbad spectrometry Analysis of Proteolytic Peptides.
"Said Hila Wolf-Levy, a first co-author," One of the key advantages of this system is that it allows us to extract information about aberrant processes in cells even from very low amount of biological material, " of this study, which was published online Nature Biotechnology.
The lupus group did, indeed, reveal a distinct MAPP profile, clearly separating them from the group of healthy subjects. In addition, the standard proteomics tests the team conducted in comparison did not reveal this division, suggesting that rummaging through the cells may be the key to gaining new insight on this disease on the molecular level.
Reviewing the current understanding
The most glaring of the proteins that have been under- or over-represented in patients' proteasomes have been members of a family called histones, which have been degraded at a higher level. Histones have several vital functions within the cell, but they have been badociated with disease, particularly autoimmune disease, when they are found in above-average quantities outside the cells.
The current understanding says that in lupus, an excess of white blood cells die, spilling their contents, including the histones, into the bloodstream. The immune system then identifies the added histone peptides as foreign antigens and undertakes its response to these particular pieces of protein.
"But these findings are taking place earlier in the white blood cells," said Merbl. "These are cells that normally take peptides from bacteria or viruses and present them on their outer membrane." "We think the cells of the lupus patients might have the same thing with the extra histone peptides, which may be degraded due to an aberration in the proteins, and may be identified as antigens by the rest of the immune system. "
These tests may be carried out in such a way that biopsies can be demonstrated in other clinical trials. conceivably make its way to hospital labs in the not-so-distant future.
The research group believes that it is possible to obtain a full understanding of the subject and to understand the role of the proteasome system.
What is exciting, but the possibilities of the MAPP method can not be avoided because of the fact that it has its own contingent of proteasomes for the breaking up of used-up and damaged proteins, the cellular "trash collection" technique could yield valuable insight. in vitro and cancer biology ranging from cancer and cancer, to basic research on protein regulation.
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