Two groups of scientists have mapped proteins in the human body
Body – library, protein – book
Ekaterina Mishchenko, <url>Scientists have compiled a list of proteins in the human body and thanks to this they were able to verify the effectiveness of several cancer drugs.
In such studies, there is a path to personalized medicine of the future, when the diagnosis of diseases and the selection of a method of their treatment will be carried out by searching for specific biomarker molecules.
Human DNA encodes a huge number of proteins, and many of them are listed in computer databases, but a clear structured map that clearly demonstrates when and where they all work has not yet been created. To remedy the situation, two independent research groups, using mass spectrometric analysis, compiled "guidebooks" to help navigate the world of the proteome.
The words "genome" and "genomics" after the "Human Genome" project are already cutting the ears of few people. But not everyone knows what a "proteome" is yet. This term is used to refer to proteins (proteins) in an organism, cell or tissue at a certain point in time. Over the past decade, the technologies that allow you to read the "text" of DNA have improved significantly: now scientists can do it faster and cheaper than before.
But to understand all the molecular processes occurring in the body, it is not enough just to know which protein is encoded by the gene – it is necessary to determine the modification and amount of this protein in a particular "duty station", since their set is very different in each organ, which is directly related to the functions of the organ.
Since any protein does not exist by itself, but is part of complex and intricate chains of interactions that determine the fate of the cell, tissue or organ in which they occur, it was very difficult to understand without a diagram or map.
"You can imagine that the body is a giant library, where every protein is a book," says Akilesh Pandey, professor at the Institute of Medical Genetics, Biochemistry, Pathology and Oncology at the University. John Hopkins (USA), founder and director of the Bioinformatics Institute in Bangalore (India). – The whole difficulty is that there is no complete catalog with the names of "books" and an indication of where to find them. I think we have now created the first scheme of this catalog."
A team of Indian researchers used in their work, the results of which are presented in Nature (Kim et al., A draft map of the human proteome), 30 samples of normal tissues of an adult organism, seven samples of germ tissues and six types of cells.
A diagram from the article by Kim et al. published on the portal Human Proteome Map – VM.
Proteins were isolated from them, which were broken down by special enzymes and with the help of the latest technologies, their number was calculated in each sample. A correspondence was established between 17,294 genes (84% of the entire genome) and the proteins encoded by them, and 2,535 of these correspondences were previously absent in common databases. In addition, the errors of the previous annotations were corrected, missing some genes or defining the expressed (active) genes as pseudogenes (non-working), and encoding RNAs as non-coding.
The most unexpected thing for Pandi's team, according to him, was the discovery of 193 proteins, the assembly instructions for which are recorded in DNA regions previously considered non-coding. This fact shows that scientists still do not fully understand how a cell reads DNA.
The second team of researchers (Technical University of Munich, Germany) in their work, also published in Nature (Wilhelm et al., Mass-spectrometry-based draft of the human proteome), studied more than 18 thousand proteins, indicating in their database their number, distribution and modifications in different types of cells and tissues.
Studying the matrix (informational) RNA, which is created on DNA and is a template for protein assembly, a German group of researchers found that each mRNA itself determines how many copies of the protein need to be produced, and the ratio is different for different proteins.
"Since we now know this proportion for a huge number of proteins, we can calculate the number of protein copies by the number of mRNA copies, and vice versa," said team leader Bernard Koester, professor at the Department of Proteomics and Bioanalytics at the Technical University of Munich.
Like the scientists from Pandey's group, Kester's group was surprised to discover hundreds of new protein fragments that are not encoded by genes currently known. On the contrary, about 2 thousand proteins, which, according to the genetic map, should exist, could not be found. According to Koester, the reason for this is the continuous change of genes under the influence of evolution.
Another important stage of the study conducted at the University of Munich was to test the effectiveness of 24 cancer drugs against 35 types of cancer cell lines. As a result, the relationship between the success of treatment and the set of proteins contained in the cells was confirmed.
The creation of two proteome maps, despite their incompleteness, greatly facilitates the work of future researchers to determine the proteins found. This makes it possible to use the results obtained by German and Indian scientists in various fields, in particular in personalized medicine, to diagnose diseases by searching for biomarkers (specific signaling molecules) and selecting a method for their treatment.
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