Eugeny D. Sverdlov#
1967—1985. Series of investigations devoted to development of methods of nucleic acids modifications and chemical approaches to determine their sequence, secondary structure and functional properties were performed. Many chemical processes that were developed in that time are used routinely in laboratory practice of the world. Fundamental principle of nucleic acids sequencing was introduced and experimentally proved in 1972—1973 (Sverdlovet al. FEBS Letters, 28, 231, 1972; FEBS Letters 33, 15, 1973). This principle is lying now in the basis of modern methods of nucleic acids sequencing.
1980—1991. Series of research works on structure and functions of bacterial RNA polymerases were performed in collaboration with laboratories of Yu.A. Ovchinnikov and R.B. Hesin. Primary structures of Е. coli, S. typhimurium и Pseudomonas putida RNA polymerases were determined for the first time. Mutations giving rise to resistance of microorganisms to rifampicin and its derivatives were discovered frist. So, nature of M. tuberculosis resistance to this antibiotic that cause severe difficulties in treatment of tuberculosis was revealed. Methods of affin modification of protein complexes with nucleic acids were developed during these researches. These methods are acknowledged all over the world and are widely used up to now, they are referred to in principal papers and reviews of the field. These investigations were awarded to State award of the USSR. RNA polymerases were determined for the first time. Mutations giving rise to resistance of microorganisms to rifampicin and its derivatives were discovered frist. So, nature of M. tuberculosis resistance to this antibiotic that cause severe difficulties in treatment of tuberculosis was revealed. Methods of affin modification of protein complexes with nucleic acids were developed during these researches. These methods are acknowledged all over the world and are widely used up to now, they are referred to in principal papers and reviews of the field. These investigations were awarded to State award of the USSR.
1986—1991. Series of investigations on structure and functions of Na, K-ATPases were performed. These enzymes are most important components of ions transport systems in animal and human cells, their damage lead to cardiovascular disorders. Structures of subunits and genes of ATPases from pig and human were determined for the first time, as well as existence of gene families coding these subunits were revealed and features of their expression in different tissues were described first. Models of functional organization of ATPase in cells were constructed.
Several works in biotechnology resulted in particular in isolation of human interferons genes and creation of recombinant bacterial strains producting these bioregulators that are important for medicine and agriculture were carried out during the same period. These works were performed in collaboration with Institute of Genetics and Selection of Industrial Microorganisms (GosNIIGenetika) and were awarded to Lenin Prize. Preparation of recombinant human interferon is used in clinics up to now.
1992—2009. Methods of wide-ranging comparative analysis of genomes of human and animals as well as their microbial pathogenes were developed. These methods are of great importance for understanding of genetic basis of pathologies and of principles of evolutional and populational genetics. A technology of suppressive subtractive hybridization is most acknowledged of them in the world. The technology allows revealing of differences between expression profiles of different genomes and tissues including tumour and normal tissues. Researches on endogenous proviruses and peculiarities of their structures and probable pathological consequences of their activity in genomes of host cells are performed at the same time. Ways of simultaneous analysis of all genomic retroviruses were designed. Wide-ranging investigation of their expression in different tissues, in tumor and normal cells is performed in present time. Series of methods allowing identification of most important functional elements of genomes — regulators of transcription, enhancers, insulators, binding sites of transcriptional factors have been developed. Identification of these elements is necessary for understanding of function of genome as integral system in processes of vital activity, of new functions arising in evolution and of their damage in different pathologies.
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