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The international forum was held at the IBCh RAS

About 700 scientists from Russia, Belarus, Uzbekistan and more than 40 foreign speakers, world-famous scientists in the field of bioorganic chemistry, molecular biology and biotechnology took part in the forum organized by the IBCh RAS together with the Russian Society of Biochemists and Molecular Biologists.

The most attended and discussed were the Keynote Lectures of the Nobel Prize laureates. The discoverer of the ubiquitin system, Aaron Ciechanover, in the report "The ubiquitin proteolytic system: From basic mechanisms thru human diseases and on to drug targeting" spoke of the activation of the transcription factor NF-kB by double ubiquitin-dependent proteolysis. The pioneer in the field of neurosignaling Thomas Südhof in his speech "Towards a molecular logic of neural circuits" presented the latest work on signal transmission in the nervous system. According to him, combinations of such trans-synaptic signaling molecules, like neurexins and latrophylins, control various aspects of the formation and specialization of synapses. The report dealt with the neurexine-3, trans-synaptic signaling platform, which determines the properties of the synapse, and latrophiline-2, the first molecule specific for the synapse, which determines its formation. Arieh Warshel, who received the Nobel Prize for "computer simulation of chemical systems," made a presentation on "The principles of enzyme aсtion" and described the methods developed by his laboratory that allow us to evaluate the activation energies of enzymatic reactions and simulate the corresponding reactions in solutions. However, despite the possibility of constructing enzymes using computer technology and the emergence of various new methods that have entered science in recent years, according to the professor, progress has not led to the creation of artificial proteins that could compete with natural enzymes.

Also Keynot Lectures were read by Professor of the Sheffield University Michael Blackburn ("How enzymes catalyze phosphoryl transfer. A great paradox solved!") and Professor Joseph Schlessinger from the University of Yale (Joseph Schlessinger, "Molecular insights into the action of endocrine FGFs offer a link between metabolic disease and liver cancer and new therapeutic opportunities").

Ариех Варшал (Arieh Warshel), получивший Нобелевскую премию за «компьютерное моделирование химических систем», выступил с докладом «Основы ферментативной активности» и рассказал о разработанных его лабораторией методах, которые позволяют оценивать энергии активации ферментативных реакций и моделировать соответствующие реакции в растворах. Однако, несмотря на возможность конструирования ферментов при помощи компьютерных технологий и появление различных новых методов, вошедших в науку в последние годы, по словам профессора, прогресс не привел к созданию искусственных белков, которые могли бы конкурировать с природными ферментами.

In addition to lectures, the forum included 17 plenary lectures and 3 plenary presentations delivered by the staff of the Institute and the forum guests: V.V. Vlasov, A.G. Gabibov, P.G. Georgiev, V.V. Govorun, S.M. Deyev, O.A. Dontsova, Moncef Zouali, Patrick Masson, K.S. Mineev (in behalf of A.S. Arsenyev), V.O. Popov, Amelia P. Rauter, A.V. Semyanov, Yuri Sykulev, Elias Toubi, Alain Friboulet, Martin Herrmann and V.I. Tsetlin, A.A. Belogurov, A.A. Vassilevski and A.V. Reshetnyak.

At the forum there were sections: " Search for New Natural Peptides and Proteins and their Isolation.

Peptidomics. Proteomics"(V.M. Govorun)," Biological Functions and Mechanisms of Action of Peptides and Proteins "(S.M. Deyev, S.N. Kochetkov)," Peptide synthesis. Protein Engineering” (V.I. Deigin, D.A. Dolgikh), "Physical-Chemical Methods in Study of Peptides and Protein Structure. "Structure-Function" Relationship" (R.G. Efremov, A.V. Finkelstein), "Chemistry and biology of enzymes" (S.D. Varfolomeev, S.D. Rumsh), "Innovative Peptide- and Protein-Based Drugs" (N.F. Myasoedov , T.V. Ovchinnikova), "Biotechnology" (V.G. Debabov, A.I. Miroshnikov).

According to one of the chairmen of the section "Innovative Peptide- and Protein-Based Drugs", the deputy chairman of the Organizing Committee, Academician Nikolay F. Myasoyedov, the successes of proteomics and peptidomics have shown that peptides not only interact with cellular systems but also cause a genome response that leads to change in the proteome and transcriptome both in normal and in pathology. Consequently, science is emerging on new targets for the action of drugs, which, incidentally, are urgently needed in the development of drugs against Alzheimer's and other neurodegenerative diseases, since leading companies are closing research in these areas. He noted that the availability of new data on the mechanisms of peptides and protein action gives us hope for an early resolution of the problem.

"If you look at how many new drugs have appeared on the basis of peptides and proteins, you will see that only one or two drugs with new structures have become available in clinical practice. This statistic makes you think. When we say "innovative drugs", we assume that they have a new structure, proven efficacy and safety of the drug. Behind these indicators is research related to the development of structure, technology and dosage form. All these are the tasks of fundamental science, since they require great research, it is here, in my opinion, academic science can say its weighty word," emphasized Myasoyedov.

Co-chair of the section "Biological Functions and Mechanisms of Action of Peptides and Proteins", corresponding member of the Russian Academy of Sciences Sergey M. Deyev agreed with the words of Nikolai F. Myasoyedov. Today, out of two thousand drugs that have undergone preclinical trials, only one goes to the clinic, and of those that have been clinically tested, there is a very large percentage of drugs with drug resistance: at some point the medications stop working. Therefore, according to professor Deyev, it is important to understand the structure and functions of molecules and substances. In his opinion, the level of research has risen high, but one should not dwell on known target preparations based on immunoglobulins and peptides, it is necessary to develop a new generation of drugs, the so-called scaffolds, that has been formed in recent years. Mechanically, these molecules cannot be compared with full-length antibodies, because they are smaller than them, and cannot be compared with peptides, because they are substantially larger and have a different physiology that is worth exploring.

"I cannot note the revolutionary changes in the study of the proteins and peptides action, because research is rather an evolutionary change. Such studies require a long time, and the object of study are molecules with a very sophisticated mechanism of action and not yet studied physiological properties. New revolutionary equipment and tools are appearing to help the researcher. Looking at them, I even wanted to temporarily become a graduate student for a while and work by my hand," admitted Sergey Deyev.

Within the framework of this section the School of Young Scientists "Studying the Mechanisms of Induction of Autoimmune Pathologies" was held within the framework of the project RNF №17-74-30019 "Structural and Kinetic Features of Antigen Presentation as a Key to Understanding the Mechanisms of Induction of Autoimmune Pathologies and Lymphogenesis" under the guidance of PhD. A.A. Belogurov and PhD. I.V. Smirnov.

Co-chairman of one of the sessions of the section "Chemistry and biology of enzymes", corresponding member of the Russian Academy of Sciences, Olga I. Lavrik highly appreciated the reports of her colleagues and separately focused on the phenomenon of protein machines – objects that consist of several enzymes and are regulated by protein factors. According to Professor O.I. Lavrik, scientific conferences should pay special attention not just to proteins, peptides and protein complexes, but also to protein machines.

The section "Physical-Chemical Methods in Study of Peptides and Protein Structure. "Structure-Function" Relationship" is not for the first time are leading by professor, deputy director of the IBCh RAS, member of the Organizing Committee of the forum Roman E. Efremov and corresponding member of the Russian Academy of Sciences, Professor Alexey V. Finkelstein. The section was different at high attendance, as well as the participation of experts who are well-known in this field, who, as noted by Roman Efremov, continue their research and, fortunately, do not go to other scientific fields. At the same time in this field there are not formed bright new scientific groups, including students under the guidance of well-known scientists.

 "We set out to collect all the studies that are present in our region in order to carry out a kind of inventory. As a result, we saw that some areas of research are very advanced today, while others have been at a high level before. However, the main thing, in my opinion, remains the question of maintaining the human resources of these research groups, and not even the presence or absence of modern equipment in laboratories or international participation. If we have specialists who are able to work with advanced, complex installations, we will be able to launch new equipment in our country," said Professor Efremov. "I think that the section lacked reports on "breakthrough" projects that would unite people who at the same time masterly owning technology and having super-tasks. This situation develops, in my opinion, thanks to the current system of grant financing organization, where a general competition is announced, often not proposing to solve a specific large task. For comparison: in 2005 our Institute was able to receive one of the first grants for the implementation of so-called complex projects for the solution of an interdisciplinary task - the development of a technology platform for the study of membrane proteins. Then Professor Alexander S. Arsenyev (project manager), together with Academician Evgeny V. Grishin, gathered specialists who possessed the necessary methods and had a clear vision of the scientific problems. They only had to be directed. As a result, many tasks have been successfully resolved, and the foundation of research has been laid for several years to come."

On the second day of the forum, the session "Ion Channels and Receptors of Nervous System: Structure, Physiology and Diseases" was held, which was organized by Corresponding Member of the Russian Academy of Sciences V.I. Tsetlin, inviting to address the leading world scientists working in this field. Professor Tsetlin emphasized that in recent years a large flow of work has been associated with cryo-electron microscopy and X-ray diffraction studies, structures with antagonist-agonists appear, and new possibilities for creating drugs open up. By the way, as it became known after the forum, the Nobel Prize in Chemistry in 2017 was awarded just for the development of cryo-electron microscopy. One of the most striking reports was the report by Professor Petr D. Brezhestovsky, the world's largest leader in the field of receptor, who spoke of Connectomics, Optic Sensorics, Optogenetics and other modern techniques, such as the use of light to color various parts of the brain.

Another session "Bioengineering of plants" was held under the leadership of Shavkat I. Salikhov, who headed the Academy of Sciences of Uzbekistan for many years. The Chairman noted the high level of the session and stressed that, on his opinion, the forum's goal was to identify competitive work and better research. In addition, Shavkat Ismailovich proposed not to limit himself to the topic of proteins and peptides and to hold a larger forum on topics in two years already in Tashkent. Academician V.T. Ivanov, with whom Salikhov communicated during the roundtable that concluded the forum, promised to support the initiative.

The Organizing Committee of the forum gave young scientists, leaders of the directions of the IBCh RAS, also address the forum participants, organizing a plenary session "Today and Tomorrow IBCh". Its speakers were: K.A. Lukyanov, I.V. Smirnov, I.A. Fesenko, D.M. Chudakov, I.V. Shelukhina and I.V. Yampolsky.

"I am glad that more and more foreign participants take part in scientific Russian conferences, the overall level of work is getting higher, the number of really great and strong Russian scientists is growing," said Ferdinand Hucho, co-chairman of the Ion Channels Session, a member of the International Advisory Board of IBCh. Concerning the topic of the forum, I believe that the most important area that the forum touched upon is molecular genetics, which is associated with various diseases. The presence of such new technologies as the analysis of genes and proteins allows us to select an individual approach to the treatment of diseases."

Within the framework of the forum, a competition of young scientists was conducted, aimed at encouraging creative activity in scientific research. The competition involved 130 young scientists under the age of 35, who are engaged in research in the field of bioorganic chemistry, molecular biology and biotechnology. The scientists presented posters, which were evaluated by the expert commission and as a result chose the 20 best papers presented on the final day of the forum in the form of oral reports. The finalists were evaluated by the commission under the guidance of Professor Tatyana V. Ovchinnikova and Professor Ferdinand Hucho.

"I am impressed by the speeches of young scientists," Professor Huho said after the awards ceremony. "For the first time I was in Russia in 1979, and at that time the level of scientific education of young people was very low, but Yuri Ovchinnikov slowly and successfully changed the situation. Now the research of young scientists is at a very good international level."

Academician A.G. Gabibov noted the value of holding such contests, allowing to broaden the horizons of young scientists, and added that further organizers of the forum would increase the level of training of young scientists for the international event by allowing reports only in English as a sign of respect to foreign guests.

Alexander Gopanenko, Junior Researcher of the Institute of Chemical Biology and Fundamental Medicine of the SB RAS (Novosibirsk), took first place in the younger age group for the report "Human ribosomal protein eL29 is a regulator of mRNA translation of genes involved in specific cell cascades."

"We showed for the first time, using the ribosomal profiling method, that an individual ribosomal protein can regulate the translation of an entire pleura mRNA. This is another proof of the hypothesis of the so-called ribosomal filter: the heterogeneity of ribosomes can provide an additional level of control of gene expression - translational," says Alexander about the essence of his work. "The contest of young scientists allows its participants to share their knowledge with colleagues, and since this activity is an important part of the scientist's work, I am glad that such competitions are held in Russia."

Stanislav Terekhov, a research fellow at the Institute of Bioorganic chemistry of the Russian Academy of Sciences, took the first place in the competition among candidates and doctors of science. He made a report "Using ultra-high-performance screening to select new biocatalysts and antibiotics from combinatorial libraries and natural biodiversity of microorganisms".

"Unfortunately, I did not manage to attend all the events of the forum, but all the reports I attended left a very positive impression," Stanislav said. "It was especially gratifying that not only well-deserved "heavyweights" of world science were present on the forum's fields: Nobel laureates, leading world experts, but also our brilliant young scientists, such as Dmitry Chudakov, Ilya Yampolsky, Ivan Smirnov, Alexey Belogurov and Alexander Vassilevski, who set a wonderful example and inspire inexhaustible enthusiasm in people like me."

Within the framework of the forum, two satellite symposia were held: "Evolution of Proteomic Studies" from Helikon Company and "Bio-Rad Laboratories" and "Integrated Structural Biology at XFEL and Synchrotron Sources" from SyncFELmed. In addition, sponsoring companies such as Dia-M, GalaChem and Merck held their master classes for participants, which, according to the organizers of the forum, were held at a decent level and attracted a large audience.

The majority of participants of the forum agreed that the event deserves high praise and, according to some Russian and foreign experts, has become one of the main scientific events in the field of Life Sciences this year in the world.

The organizers did not confine themselves to the audience present at the forum: plenary lectures and reports were recorded and, as far as getting consent from the speakers are posted on the Internet. Actual lectures of all three Nobel laureates are already available for listening. In the near future, other plenary lectures and reports of leading scientists of the world and Russia, who took part in the forum, will be posted on the network. The current information about the forum is available on the website of the Russian Society of Biochemists and Molecular Biologists. The materials of the forum were published in the special issue of the journal ActaNaturae, which is also available for downloading on the website of the Society.

 

Andrey Reshetnyak' Lecture

Alexander Vassilevski's Lecture

Vadim Govorun's Lecture

october 12, 2017

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