01 July 2013

Russian and European scientists create innovative medicines together

Promising results

Ekaterina Sarul, newspaper "Search" No. 26-2013

In 2012, the Russian Foundation for Basic Research and the European Laboratory of Molecular Biology (EMBL) decided to support six international projects aimed at creating innovative medicines. Scientists have already achieved the most interesting results, research on all grants is actively continuing.

Alexey Egorov, Head of the Laboratory of Engineering Enzymology of the Chemical Faculty of Lomonosov Moscow State University, Academician of the Russian Academy of Medical Sciences, tells about the preliminary results of the joint RFBR and EMBL competition.

– Alexey Mikhailovich, you took an active part in the expansion of international cooperation of the Russian Foundation for Basic Research and, in particular, in the preparation of an agreement with EMBL. How was the idea of a joint competition born?

– The European Laboratory of Molecular Biology is in a certain sense an analogue of the well–known international scientific center in Dubna. It includes 20 European states and a partner country - Australia. According to the number of scientific publications and the citation index in the field of molecular biology, EMBL ranks fourth in the world and first in Europe. The organization supports almost 100 projects in various areas of research.

At the moment, our country is not officially a member of EMBL, which, however, does not prevent us from successfully cooperating. About 30 Russian research groups participate in EMBL projects as partners.

An important step was the signing in 2011 of an official agreement between the RFBR and EMBL, according to which the foundation received the right to participate in the organization of joint research.

We have chosen a serious partner, and this has opened up a lot of new opportunities. This applies to the research itself, publications in prestigious international journals, and the commercialization of scientific results.

The signing of the cooperation agreement was preceded by two conferences: in Germany and in Russia. Last year, the first competition was held, 12 applications were received, half of them received support. The third conference held this year was dedicated to the results of the competition.

– Only a dozen applications? Not enough?

– Only groups that already have links with EMBL and experience working on international projects participated in the competition. We did this consciously, by agreement with our European partners.

– What gives our scientists such cooperation?

– Within the framework of the agreement, it became possible not only to conduct joint research, but also to pose and promote certain scientific problems. This in itself is extremely important. Our scientists are regularly invited to work on unique equipment in EMBL laboratories located in Hamburg, Grenoble, Heidelberg and other major European scientific centers.

The psychological factor is also important. Cooperation imposes strict obligations. There is a plan, there is a schedule, you can't work carelessly. Many joint events are useful: symposiums, conferences, congresses, where there is an active exchange of views. This year, a large scientific meeting was held, where reports on each of the projects were listened to. Everyone got to know each other, such a kind of scientific club was formed.

This summer, from July 6 to 11, another important event will take place – the Congress of the Federation of European Biochemical Societies (FEBS-2013). This is a unique event, like the Olympic Games, only for biochemists. In our country, such a congress was held only once – in 1984. We are waiting for all the EMBL management to visit, we will discuss further prospects of cooperation.

– Please tell us about the supported projects.

– Scientists from several institutes of the Russian Academy of Sciences and faculties of Moscow University participate in joint research. On the part of the European partners, Viktor Lamzin, Deputy Head of the EMBL branch in Hamburg, is one of the initiators of the cooperation program, and I am from the Russian side.

Among the supported works is the project of the Laboratory of Biochemical Genetics of the Institute of Molecular Genetics of the Russian Academy of Sciences "Epigenetic control of genes carried out with the participation of short RNAs in insects", which is led by Academician Vladimir Gvozdev, Head of the Department of Molecular Genetics of Cells of the IMG RAS. The results obtained during the research can be used to study epigenomic cancer modifications of chromatin in human tumors.

Another project is the joint work of the groups of Candidate of Biological Sciences Vsevolod Belousov from the Institute of Bioorganic Chemistry named after M.M.Shemyakin and Yu.A.Ovchinnikov of the Russian Academy of Sciences and Carsten Schultz from EMBL, studying the mechanisms of transmission of oxidative and lipid signals in the cell. It is hoped that the research will lead to the development of drugs aimed at the production systems of reactive oxygen species.

Another work is a joint project of the Biocatalysis laboratory of the Institute of Bioorganic Chemistry of the Russian Academy of Sciences and EMBL, aimed at studying structural and functional interaction in artificial enzymes. The research is led by Corresponding Member of the Russian Academy of Sciences Alexander Gabibov. The use of the richest crystallographic base of EMBL and the methods proposed by our scientists allowed us to get answers to many fundamental questions related to the structure and activity of antibodies. Antibody-based drugs are widely used in modern medicine, and the results of this study have obvious practical significance.

A promising project of EMBL and the Laboratory of Nucleotide Chemistry of the Faculty of Chemistry of Lomonosov Moscow State University is devoted to the study of the structural characteristics of proteins of the H. Polymorpha telomerase complex, which is very important for understanding the mechanisms of cell division. The head of the study is Olga Dontsova, Head of the Department of Chemistry of Natural Compounds at Moscow State University, Corresponding Member of the Russian Academy of Sciences. The data obtained during the project should open up fundamentally new opportunities for the development of antitumor drugs.

The project of the team of Academician Pavel Georgiev from the Institute of Gene Biology of the Russian Academy of Sciences and the EMBL laboratory in Heidelberg "Identification of new transcriptional regulators of early embryonic development" is interesting. The study of the mechanisms that determine embryonic development, the laying of tissues, will allow you to quickly uncover the secrets of the regulation of genetic processes.

Well, a few words about the project of our Laboratory of Engineering Enzymology of the Faculty of Chemistry of Moscow State University "Search for new beta-lactamase inhibitors to overcome bacterial resistance to antibiotics", aimed at forming new approaches to overcoming antibiotic resistance (the ability of microorganisms – pathogens of infectious diseases to develop resistance to antibiotics). The Russian group of scientists is led by Candidate of Chemical Sciences Vitaly Grigorenko.

To be honest, if we had done this work on our own, without European partners, it would have taken 20 years. And it is unknown whether there would have been a result or not. And so we made a huge leap in a year. EMBL already presents our results at international exhibitions.

The substances created in the framework of the joint project are inhibitors of enzymes that destroy antibiotics. Their use increases the effectiveness of drugs.

The work is large, it is divided between two groups. In Germany, they professionally do what they can, and we do our part of the research. At the same time, we observe a clear synergistic effect: the case is moving surprisingly fast.

Our partners from EMBL have developed a computer program with the help of which the drugs we need are selected from a data bank containing eight million molecules. As a result, they managed to find 550 molecules.

To study the activity of these molecules, a robot is used, which pours into special containers the genetically engineered lactamase developed in our laboratory and adds molecules from among the selected ones to it. We find out how they affect lactamase. At this stage, the selection is already much stricter. In our case, only five molecules have passed it. Imagine the statistics: five out of eight million!

Then, using computer modeling, we determine how these molecules bind to the enzyme lactamase, and study their interaction in detail. It turns out that two of the five substances are active: but their activity is higher than that of those currently used in pharmaceuticals.

In general, it is believed that it takes 10 years and a billion dollars to create a new drug. Within the framework of the project, two highly active molecules were found in one year. From the point of view of toxicity, they are not dangerous. And, therefore, promising for use in medicine.

By the way, now the enzyme developed in our laboratory is used in Germany to obtain crystals and X-ray diffraction analysis. This is a very delicate job. Lactamase constantly mutates and changes its structure, but there are areas that remain constant. We are looking for a universal inhibitor that acts on these permanent sites, and we continue to search and study new highly active molecules.

– Will the interaction with EMBL continue?

- Yes. Our colleagues are very pleased with the cooperation and are interested in its development. All joint projects are aimed at creating innovative medicines, and we have significant results. Many of them are already being presented at prestigious international pharmaceutical exhibitions.

There is an opinion that our scientists at the Academy of Sciences have never thought about the effectiveness of their research, about economics... nonsense, we have always thought about it! There was such a word – "implementation". Now it's called "technology transfer".

The specialized organization Enterprise Management Technology Transfer GmbH (EMBLEM) operates under the auspices of EMBL, which deals with a very wide range of issues – patenting, organization of joint companies, technology transfer, sale of licenses, in general, commercialization of science. Everything was done very intelligently, we should have adopted this experience.

This year, the work will continue within the existing framework. And in the future we hope to receive new grants under the joint program of oriented fundamental research of the RFBR and EMBL.

Portal "Eternal youth" http://vechnayamolodost.ru01.07.2013

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