Molecular biology in Russia is still alive in some places
A well - aimed squirrel
Pushchina scientists are shooting a new weapon against cancer cells
Firyuza Yanchilina, the newspaper "Search" No. 4-2011
There is a lot of talk today that the Russian pharmaceutical industry needs urgent resuscitation. Enterprises produce, as a rule, cheap medicines, the substance for which is mainly imported from other countries. One can only dream about new drugs so far. Meanwhile, research institutes are carrying out work that can raise the domestic pharmaceutical industry. An example of this is the Institute of Biological Instrumentation (UPS) of the Russian Academy of Sciences in Pushchina.
Previously, it was the scientific and production association "Biopribor". In the 1990s, when employees did not receive a salary for months, it was about the bankruptcy of a self-supporting institution. They decided to transform it into an institute, allocated money from the state budget. Evgeny Permyakov, Doctor of Biological Sciences, was offered to lead the UPS.
– The building was in very poor condition, – recalls Evgeny Anatolyevich. – The walls were scuffed, the sockets were turned out, the roof was leaking. During the rain, employees ran to the laboratory on the upper, fourth, floor to cover the devices with polyethylene.
The institute has changed a lot in recent years. The entire fourth floor is occupied by the laboratory of new methods in biology, organized, like the institute, in 1994. The premises have been renovated, modern equipment has been purchased. Most of the money was received under the program of the Presidium of the Russian Academy of Sciences "Molecular and Cellular Biology". As E.Permyakov notes, the equipment of the laboratory is now at the level of American and European.
Good conditions allow scientists to work in the most relevant areas of biophysics, and at the world level. Among the factors hindering research is the inability to obtain the necessary reagents in a timely manner, 95% of which are imported. If scientists abroad receive the necessary reagents, as a rule, the very next day, or at most a week later, then Russian scientists have to wait two to three months, while the price is usually one and a half times higher than in the West. Nevertheless, even this problem does not prevent the laboratory staff from achieving significant results in their field.
The peculiarity of the laboratory is also that one of its scientific groups, which is engaged in protein research, consists of 70% of employees under 35 years of age. These are graduate students of the Russian Academy of Sciences, undergraduates and postgraduates of Pushchina State University, young scientists. There are seven candidates and four doctors of sciences in a group of 20 people. Thanks to the youth staff, the group manages to receive grants for programs for young scientists of the Ministry of Education and Science.
Sergey Permyakov, the son of the director of the Institute, has been leading the group for the fourth year: a scientific dynasty is emerging. Sergey started working at the Institute as a student of the Faculty of Physico-Chemical Biology at MIPT. He defended his diploma here, then his PhD thesis. In principle, there is enough research material for a doctoral degree...
– In parallel, we are conducting several areas of work, – says the head of the protein research group S.Permyakov. – A sufficient number of qualified specialists and modern equipment allow us to study our facilities in a variety of ways.
By the way, research that is initially purely fundamental in nature often brings unexpected "applied fruits". Working in 1993 at the Ohio State University, Evgeny Permyakov, together with an American graduate student, studied the properties of the milk protein α-lactalbumin. They investigated, among other things, the possibility of interaction of this compound with fatty acids. It turned out that they bind, forming stable complexes. The scientists published a report about this, which seemed to be of purely theoretical interest, in a scientific journal. Three years later, Swedish researchers discovered that the complex of α-lactalbumin with oleic acid has pronounced anti-cancer activity. Moreover, preclinical and even clinical trials of a new potential drug have begun. The complex was named HAMLET (an abbreviation of Human Alpha-Lactalbumin Made Lethal to Tumor Cells, which translates into Russian something like this: "Human Alpha-lactalbumin, deadly to tumor cells"). A boom began in the world, and many laboratories began to study the properties of a new drug. Evgeny Permyakov also returned to this topic, but already within the walls of the Institute of Biological Instrumentation. It was possible to develop a simple and effective technology for the production of a protein complex, which, among other things, simplifies the process of standardization of samples (the Swedes received the substance in a less productive way).
In the protein research group, HAMLET technology was used to bind other proteins to fatty acids. Moreover, other classes of compounds can be used instead of acids. Scientists expect to significantly expand this scientific direction. Many of the complexes obtained in the future can also show medicinal properties and raise medicine to a new level. After all, it is known that anti-cancer chemicals used today cause serious side effects. Natural proteins can be not only more effective, but also have a milder effect on the body. To identify new possibilities of connections, you need to understand and study a lot. The first steps have already been taken. Using electrophysical research methods, Pushchinsky scientists have found out how complexes with fatty acids "cut" holes in membranes, contributing to their penetration into the cell. A message about this was immediately published. Then there were publications about similar works by Western biologists. But the priority remained with Russian specialists. The Pushchin team also discovered that α-lactalbumin is able to interact with histones (proteins inside the cell nucleus that are designed to "pack" DNA), as a result, the cancer cell is programmed for apoptosis (death). However, the mechanism of such an effect on cells is not yet fully understood – it remains to be found out.
Another area of work of the scientific group is promising research related to the so–called natively unfolded proteins. It is written in all textbooks that proteins become functional only if there is a strictly defined spatial structure. Studies of the last 10 years have shown that proteins without rigid spatial organization also play an important biological role. They become structured only when interacting with different compounds or other proteins. Now this is a completely new paradigm in protein science, which is widely discussed and developed in the world. The result may be the creation of a new class of medicines. One of the founders of this bright, promising direction is an employee of the laboratory, Doctor of Physical and Mathematical Sciences Vladimir Uversky. Director of the Institute Evgeny Permyakov is sure that Vladimir Nikolaevich's works deserve the highest awards, including the Nobel Prize.
Metal-binding proteins that have been studied in the group for a long time, for example, proteins of the S100 family, can also be natively uncoiled. They are relatively small and, as a rule, are in dimeric form (a complex of two molecules). But they have an interesting property – the ability to bind about two hundred other proteins, which is a sign of native non-folding. Theoretical and experimental studies have confirmed this. Now S100 proteins are used as markers in the diagnosis of many diseases. But in the future they can be used for the effective treatment of a wide range of ailments: neurodegenerative, oncological, inflammatory diseases, cardiomyopathy, etc.
The laboratory staff has achieved some success in studying the functioning of the visual system. Scientists are interested in the role of calcium-binding proteins in this system, for example, recoverin. This protein functions at the stage of relaxation of the visual system, which follows after the stage of excitation of receptor cells by photons of light. Pushchinets, as well as their colleagues, managed to show that the functioning of this protein can be regulated by the state of oxidation of its only cysteine residue.
Living organisms continue to amaze with their complexity. Previously seemingly "insignificant" substances, it turns out, sometimes play a very important role in subtle mechanisms. Therefore, one of the most important tasks of scientists is to find out the functions of proteins.
– Only by finding out what a particular protein is needed for, the mechanism of its action, we can influence the process in which it participates, – explains Evgeny Permyakov. – Therefore, in order to create drugs, it is necessary, first of all, to investigate how the cell works, which is still inexhaustible for scientists. It is necessary to understand what is normal for this structural unit, and what is pathology, how a healthy cell turns into a malignant one and how this process can be stopped.
For a deeper and more detailed study of proteins inside the laboratory of new methods in biology, another direction is developing – cellular research. A "clean room" is already equipped for this purpose, the necessary installations and devices are being purchased. The invited specialist begins work. A new stage of scientific research will help bring the domestic pharmaceutical industry to a higher level. In any case, I would really like to believe it.
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27.01.2011