Department of Biomedical Research

Mogylevych Sergiy Yevgenovych, PhD in biology, Senior research fellow.

The contact information:
Address - 1, Murmanska Str. Kyiv-94, 02660, Ukraine
Tel. (38044) 573-25-90, fax (38044) 573-25-52
E-mail: mse@bpci.kiev.ua

Scientific direction of work of division: The basic direction of work of a department is the study of the most general regularities of xenobiotics influence on living cell with use of supramolecular and cellular models, as well as methods of computer chemistry.

Perspective researches and development, information about which is supposed to be placed on a site of Institute
As it was established by Prof. A.I.Luik, administration of sulfur mustard to animal organism initiate the appearance of some factors possessing high physiological activity. In particular, its most expressed effects are the hemopoiesis stimulation and strongly pronounced stimulation of the humoral and cellular immunity. Immuno- and hemostimulating effects of this factor were studied by administration of serum or certain tissue extracts of correspondingly pretreated animals in the intact organism and in experiments in vitro on blood and spleen cells as well. The same material was investigated on mice with Lewis lung carcinoma and rats irradiated with lethal doses of ionizing radiation or against a background of administration of high doses of alkylating chemopreparations. Investigation results are evidence of material activity sufficient for its more detailed study as envisaging further development medical preparation.
The further research has shown, that the ability to stimulate formation of immunostimulating factor in blood of experimental animals is inhered not only to sulfur mustard but to broad range of other less toxic compounds. It was predicted with computer methods of artificial intellect and confirmed in experiments on specific models.
Taking into account some features of technology of production of the mentioned factor, which have protein nature, it is expedient to consider questions of completion of development, manufacture and application of a biopreparation only after confirmation that this material can essentially raise efficiency of therapy of diseases which are difficulty treated by usual methods: malignant tumors, heavy immunodeficiencies, chronic infections, pathology of hemopoesis, affection by ionizing radiation. In case if on a background of such pathologies any unique properties of a preparation will be revealed, that can be expected on the basis of results of a preliminary estimation, the development of technology of its isolation from biological raw material, industrial manufacture and medical use is represented quite real. It is necessary to emphasize, that if in experiments with integral serum the encouraging results will be received, efficiency of a preparation will be raised on some orders after isolation of active substance in the pure state .
Taking into account above-stated, we offer for study lyophilized serum of rats, subjected to special processing. A preparation is practically not toxic. At its intraperitoneal administration to mice in a doze up to 2000 mg/kg any toxic effects were not observed.
Another direction of investigations is concerned with the study of the influence of known physiologically active compounds (PAC) on monolayers of various composition formed on water surface. Earlier under a management of Prof. A.I.Luik large scope of experiments on tissue and cellular models was carried out which has allowed to substantiate a hypothesis of bioregulatory stereotypy. According to this hypothesis the bioregulatory stereotype is defined by direction of PAC action (activation or inhibition) on the main signaling cascades of a cell - adenylate cyclase and polyphosphoinositide. It is inherent in the overwhelming majority of known PAC. With use of the cluster analysis and method of neural networks we succeeded in showing, that the PAC division into two classes according to bioregulatory stereotype, substantially coincides with their division on influence on physico-chemical parameters of phospholipid and protein monolayers.
The third direction of investigations is concerned with development and application of robust statistical methods for search of relationships between chemical structure and biological activity of PAC (3D-QSAR). These methods include construction of predictive spatial models which represent compound properties causing established kind of biologic activity, development of software tools for 3D visualization of results as well.
Development of mathematical algorithms and software engines to develop predictive QSAR models on the base of artificial neural networks, hierarchical cluster analysis, genetic algorithms are carried out. For creation of software tools for analysis of chemical compounds (building and calculation of molecule descriptors, QSAR) modern internet technologies are widely used (international project Virtual Computational Laboratory, see http://www.vcclab.org).
6. Additional information about department

THE LIST OF TASKS, WHICH CAN BE SOLVED IN THE DEPARTMENT OF BIOMEDICAL RESEARCH
1. Investigation of ligand-receptor complexes. CoMFA, MFA, PLS methods, genetic algorithms.
2. Division of sample of compounds into any number of classes by neural networks, cluster analysis without training sample of the data.
3. Prediction of system parameters change on the basis of their values at present time (forecast of the future behaviour of system).
4. Forecasting of physico-chemical properties and biological activity of substances proceeding from available parameters (topological indexes etc). Revealing of quantitative structure-activity relationships (QSAR). Selection of the characteristics most influencing display of a given kind of activity. Search of pharmacophores.
5. Forecasting of compounds biological activity (toxicity and other properties) proceeding from their spatial structure (3D-QSAR). Revealing of zones in space around of the molecules causing a given kind of activity. Visualization of results.
6. Analysis of the spectral data. Identification of compounds on the basis of spectral data. Resolution of spectra of a mix on spectra of individual components using artificial neural network (ANN) methods.
7. Development on the basis of ANN models of the programs for quality control of technological processes. The application of mathematical models on a basis of ANN allows to make transition from diagnostic signals to individual parameters of technological process and to develop the effective mechanism of their control and regulations.
8. Development of the programs for the analysis of chemical compounds (construction of structural models and calculation of molecule parameters, search of interrelationships between structure and various kinds of compound activity) with use of modern Internets - technologies (international project Virtual Computational Chemistry Laboratory, details on a site http: // vcclab.org).

Study of such kinds of biological activity of chemical compounds also is possible:

1. Estimation of influence on humoral part of immune system -

• Reaction of direct and indirect hemagglutination;
• Determination of spleen antibody forming cells amount;
• Reaction of direct and indirect rosette formation;

2. Estimation of influence on cellular part of immune system -

• Reaction of hypersusceptibility of the delayed and immediate types;
• Reaction spleen lymphocytes blasttransformation;
• Migratory activity of macrophages;

3. Estimation of influence on parameters of organism nonspecific resistance -

• Activity of lysozyme;
• Phagocytary activity of neutrophyls;
• Spontaneous and stimulated neutrophyls motility;
• Complement determination