Unique technology will help treat brain diseases

A molecule with a trailer

Yuri Drize, newspaper "Search" No. 51-2013

The outgoing year turned out to be very successful for the Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences. Several articles describing experimental work have been published in the leading, top-rated foreign journals in the field of neurophysiology (one of them belongs to the American equivalent of our academy). One piece was so unique and innovative that the reviewers rejected it: they simply did not understand the meaning. The director had to write a letter to the editor to explain the essence, then they figured it out and accepted. On this wave, the Institute decided to participate in the prestigious competition of the Russian Foundation for Basic Research "Complex interdisciplinary fundamental research in the field of molecular and cellular organization of biological structures and processes" ("COMFI") and became one of the winners. The purpose of the contest is the most important: the search for fundamentally new approaches to the analysis of the brain and the fight against neurodegenerative diseases, such as Parkinson's, Alzheimer's, and other less common. Winning this very important competition was as difficult and honorable as being published in foreign magazines.

Pavel Balaban, Director of the Institute, Corresponding Member of the Russian Academy of Sciences, tells:

– The competition is really difficult. After all, its mandatory condition is to assemble a team of four scientific organizations that would complement each other and, most importantly, correspond to the world level. If one of our four had not had publications in well-known specialized journals, we would not have seen victory.

– And under such a strict condition, you still found competitors?

– Yes, and a lot: as far as I remember, about 200 projects applied for about 20 places. And this is not surprising: the level of biomedical research in our country is extremely high.

This applies to molecular biologists, physicists, and physiologists. Physiology is traditionally ahead, especially that area of it that studies the brain. I am proud: our application was in the top five. Therefore, I think that we have an extremely strong group: in addition to our institute, the project coordinator, it includes physicists of Moscow State University – specialists in optics in relation to biology, molecular biologists from the Institute of Bioorganic Chemistry of the Russian Academy of Sciences named after M.M.Shemyakin and Yu.A.Ovchinnikov and physiologists studying higher brain functions (SIC "Kurchatov Institute"). Only together can we try to find new, never-before-explored ways to treat neurodegenerative diseases. The known approaches, it must be admitted, have already exhausted themselves. Work on this topic is also being carried out in the West, in the most powerful laboratories, and is considered a priority. The National Institutes of Health of the USA (National Institutes of Health) allocate from 10 to 100 million dollars a year for similar projects. And, alas, our funding was cut three times: of the three million rubles promised by the RFBR, each participant will receive one (the grant is designed for two years).

– What can be done with such modest funds?

– Practically nothing. You can't buy a device with them. I think we'll just give the money to the participants in the form of a bonus.

– It is known that scientists all over the world have been conducting research in the field of neurodegenerative diseases for decades – and in fact to no avail. Why?

– That's right. Not a single patient could be cured. The reason is the complexity of studying the brain: it is still a mystery to science. The trouble is also that these diseases are extremely common: after 50-60 years, tens of percent (of the total population) of patients are added. Hundreds of millions of people in the world suffer from these chronic ailments. And, alas, these diseases are incurable. Medications can only slow down the development of the disease and facilitate its course, since they cannot fight the cause, which is still unknown for certain. Therefore, people are not able to overcome the disease yet.

As a result, the total cost of treatment of neurodegenerative diseases far exceeds the costs of cardiovascular and oncological. This year, the European Union has added over a billion (!) euros to the funds already allocated to combat the first. Even at the G8 meeting, the situation related to brain diseases will be discussed: how to better coordinate research in this area and promote it. For G8 members, this is an important political issue, not least because of the huge cost of treatment. And the RFBR contest pursues almost the same goals: it forces us to look for like-minded people to fight these ailments in our country and join forces. After all, sometimes we are more familiar with the works of colleagues abroad than with the works of compatriots.

– Is it known what causes these diseases in the brain?

– The human brain is quite plastic. Unlike the animal brain, it has a much larger volume, and therefore has virtually unlimited opportunities for learning and creativity. But, as it turned out, under certain conditions that have not yet been clarified, the brain can develop in a positive way, for example, it acquires skills, the ability to perceive and analyze. And in some cases, perhaps isolated, neurodegenerative diseases occur.

– It seems that everything depends on the "switchman": where will the mutating gene direct, in that direction will brain development go?

– Approximately so, but unfortunately, the gene is not alone. And age, first of all, leads astray from the right path. Under its influence, the work of the brain changes, regulatory mechanisms do not work – and the "arrow" is transferred to the wrong place. But it is extremely difficult to understand what kind of "push" is happening in the brain, to understand its causes and consequences, because hundreds of billions of nerve cells need to be examined. Therefore, it is necessary to find and create fundamentally new technological methods. The existing ones are clearly outdated – they only recorded the activity of individual cells, trying to study genetic regulation at the level of individual neurons, and this is already a passed stage, and we are not moving forward.

– And in what direction are you developing research today?

– We have been trying to find a new way for fifteen years and have come to the conclusion that the most promising direction is to try to see how the physiological processes in the brain proceed. For this, we have a brilliant opportunity to find, isolate the most important molecules working there, and literally attach to them particles (molecules or proteins) that have the ability to glow. With the help of such markers, we will know exactly how cells act. Let's find out how, say, during training or other very different loads, physiological changes occur. And with the help of a special microscope – and this is the task of optical physicists - we will try to penetrate into a sufficiently dense brain tissue by 1-2 millimeters. At micron resolution, we will see how and where the molecules move, understand their behavior, trace their fate. Then, I hope, we will understand how there is a deviation from the normal, healthy path. To observe this stunningly interesting, never before seen by us process in a living cell is an outstanding achievement.

– Yes, it's the Nobel Prize!

– Perhaps, if, of course, it is possible to find the "switchman". After all, there are thousands of such molecules, and our task is to determine which of them are the most important and are responsible for those changes that make the brain more plastic, receptive or, conversely, lead to deterioration of its activity and diseases. This is a fundamental point. But discovering the molecules that "control movement" is only the first step. The next step is to learn how to regulate their work, and if necessary, to suppress them. There are many ways to do this. Somewhere – to slow down, somewhere – to activate the work of the cell. Of course, not everything is so simple, but the path is already roughly clear. If this method justifies itself (and there is no clarity to the end yet), then a perspective will open up. Knowing the root cause of diseases and the mechanism that causes them, it will be possible to connect technologists. Having decomposed these processes into molecules and atoms, they will create new drugs. We will establish these connections through participation in COMFI.

– And what does it mean to "attach a particle of a molecule", how is it done?

– To do this, a viral carrier is inserted into the genetic apparatus of the cell, which, as is known, has the ability to penetrate anywhere. A gene of a glowing harmless protein molecule is attached to the carrier. It turns out that the marking biological mechanism is embedded in the right place, for example, next to the gene under study. Now, by the glow, it will be possible to learn about the work of the genetic apparatus, to trace the physiological reactions of the cell. This most difficult task is successfully solved by the Institute of Bioorganic Chemistry of the Russian Academy of Sciences.

– How long will it take approximately to develop this unique technology?

– Unfortunately, the RFBR grant was given for only two years, but it needs five years. We won't do anything in less time. And although today the development of these methods is literally leaps and bounds, still, I think it will take us ten years to find new approaches to the treatment of neurodegenerative diseases. So far, it is necessary to detect all the genes that change after the aforementioned "fork". It will take a lot of effort to develop an effective technology for "sewing" luminous particles to a molecule. We need modern microscopes, and they cost 1.5-2 million dollars. They are in our group, but not all the participants. However, thanks to the grant, our entire team will use them – this is the meaning of the association.

In addition to microscopes, a whole range of various equipment and reagents is also needed. And to work with all this complicated "economy", you need to study a lot, so the training of such employees is a whole problem. Even for the West, even for the most advanced universities and laboratories in the world. I get a lot of requests from foreign colleagues: send a specialist – we are unable to adjust the device or master the technology of markers. Commercial firms, universities, as they say, will tear off such employees with their hands and pay them very good money.

– And what do you lack, besides money, of course?

– A very simple answer: respect. Scientists are not respected. Science, I am sure, selects almost the most capable, intelligent people. And most of them go to officials by acquaintance, by blat. But it is these people, who have practically no qualifications, who undertake to manage science, decide what scientists should do. This is terrible! Also, of course, the unknown worries: how long will the uncertainty that has arisen in connection with the reorganization of the RAS last? Among young people, this causes progress – many employees are thinking about leaving. They ask me for recommendations, and I can't refuse. I'm afraid we will soon lose at least half of our best young cadres. The failure that our science experienced in the mid-90s of the last century will be repeated. But I cannot condemn young people for wanting to live with dignity.

Portal "Eternal youth" http://vechnayamolodost.ru26.12.2013