LABORATORY 12
Laboratory of Bioinformatics of Cell Processes
and Motocontrol
Head of Laboratory – Dr.Sc. (Math.) Alexey Chernavsky
Tel.: (095)209-42-25, (095) 952-33-03; E-mail: chernav@iitp.ru
The leading researchers of the laboratory include:
Corresponding member of Russian Academy of Science L. Chailakhian |
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Dr.Sc. (Biology) |
Yu. Arshavsky |
Dr.Sc. (Biology) |
Liberman E. |
Dr.Sc.(Biology) |
M. Berkinblit |
Dr.Sc.( Math.) |
Lukashevich I. |
Dr.Sc. (Biology) |
V. Bozhkova |
Dr.Sc. (Biology) |
Minina S. |
Dr.Sc. (Math), |
V. Dunin-Barkowsky, President of the RNNS |
Dr.Sc. (Biology) |
Samosudova N. |
Dr.Sc.(Biology) |
Z. Khashaev |
Dr.Sc.(Biology) |
Panchin Yu. |
Dr.Sc. (Biology) |
I. Keder-Stepanova |
Directions of activity
The general theme of the scientific work in the laboratory is: the analysis of information processes in cellular systems and in motor control. The main directions of theoretical researches in this realm: developmental biology (analysis of principles for the realization of genetic information in the developmental systems), neurobiology (neural communication and biochemical modulation in neural centers), motor control (study of geometry of manipulative space and of control for goal-directed movements). Also some new bioinformatical principles are worked out including the building of computerized system for the analysis of expert work.
MAIN RESULTS
Developmental biology. In the Dr. Bojkhov's group the mechanisms of development are studying, which cause the appearance of the space-ordered differentiation of cells. As a complement to the now largely studied principles of genetic programming there is shown the meaning for the cell differentiation of the information which come into cells through intercellular connections and primarily through the highly penetrable (gap) junctions. With genetic mutants an assumption was confirmed that the local specificity of penetrability of gap junction channels in embryo is subject to morphogenetic gene control. In this experiments the mutants flh of the line b237 were used. (They were received through the International Union for the Genetics and Development from V. Korzh, Singhapour Institute of Molecular Biology.) These results approve the hypothesis about the connection between gap junction and space order in cell differentiation and also display a path to study the regulative system of gap junction properties on genetic level. Also those developmental stages in fish embryos were brought to light where the activity of phosphatidil-inositol system become apparent.
The properties of the plasmatic membranes have different important roles in the cell processes including pathological ones. Earlier, by I. P. Plonsky it was shown with the fusion proteins of baculovirus (GP64) and virus of grippe (HA) that the properties of the initial fusion pore are determined with the fusion proteins and not by the mechanical characters of the membranes depending on their chemical composition. Now it was ascertained that pores formed with different virus proteins differ one from other. A study is prepared aimed to synthesize molecular chimeras – the hybrid molecules that contain aminoacid sequences HA and GP64, and then to decide with what sites of the sequences the different properties of pores are determinate. (In collaboration with the Laboratory of Cellular and Molecular Biophysics, National Institutes of Health, USA).
Ju. V. Panchin has characterized a new gene family for gap junction proteins named Pannecsines. They were cloned from the DNA of human, mouse, mollusk Clione and planarian. In human and other mammals they are expressed mainly in the head brain, it is supposed that their mutation are connected with serious pathologies of the CNS.
Neurobiology. The neural system, a base of informational interaction of manycellular animals, was studying in the laboratory at different levels.
This year a large study by a group guided by Y. I. Arshavsky was finished, which concerned neural mechanisms underlying orientation of the marine mollusc Clione limacina to the gravity field. The functional organization of nervous mechanisms responsible for the postural control system in vertebrates is extremely complex. An advantage of Clione for such kind of studies is that it, being a gastropod mollusc with a "simpler" nervous system, exhibits rather complex behaviour, swimming in 3-dimentional space. It has been shown that the neural network controlling Clione spatial orientation model has hierarchical organisation. The gravitational receptor organs, statocysts, send signals to the cerebral ganglia where they affect the cerebro-pedal interneurons controlling tail and wing motoneurons. Spatial orientation is achieved due to co-operative activities of tail and wing motor systems. The networks controlling mollusc orientation combine a high robustness providing the generation of a stable spatio-temporal output in the presence of noise and accidental disturbances and a high flexibility providing an adaptability of the control system to changing conditions. Several modes of Clione’s spatial orientation determined by a functional reconstruction of connections within the postural control system have been found. Depending on the water temperature Clione takes the orientation head up (at lower water temperature) or head-down (at higher temperature) to move to a layer with a suitable temperature. When some object touches its head a complete inhibition of postural activity takes place and it sink head-down. Clione spatial behaviour changes radically during hunting. The direction of tail flexion is not constant but changes in a random manner with time. An impression is that Clione "scans" a surrounding space to catch the prey. It has been found that GABAergic mechanisms are involved in organisation of hunting behaviour. (In collaboration with Institute of Neurobiology, University of Puerto Rico and Nobel Institute for Neurophysiology, Karolinska Institute, Stockholm, Sweden.)
Dr. I. A. Keder-Stepanova's group studies changes in the activity of the medullary respirator nuclei in ontogenesis. The neuron activity was recorded in slices from newborn mices (1-10 days). The additional data was collected which affirmed absence of the endogenous synchronized burst activity, that is, there occur in the same slice neurons with different periods of burst activity. Such activity disappears up to 7-8 day and the neurons of respiratory nuclei works continuously with different and not constant frequency. To analyze this activity it is conveyed into computer and also histograms of interimpulse intervals is derived on base of instantaneous measurements (the program of V. Olshansky). In this experimental conditions one successes with discovery of implicit period types.
An analysis of the neuron mechanisms of the medullary respiratory center was carried out also by W. L. Dunin-Barkowski. The excitatory drive of the center during the paradoxical sleep in cats was studied with artificial breath and with variations of breathed gas mixture. The work on a complete neuron model of the respiratory center is begun.
The cerebellum occupies the central place in organization of movements. Its study is the traditional theme of the laboratory. In particular the perennial investigation of the Purkinje cells is carried out by the W. L. Dunin-Barkowski's group. This year the work in analyzing impact of the climbing fibre on the Purkinje cell. The influence of the nonlinear properties of Purkinje cell on the cerebellum module is examined and it is found out that the equalization on the climbing cell enter may occur also with nonlinear dependence of the Purkinje cell exit on its enter. The prolonged records of Purkinje cells' activity in form of complicated impulses was analyzed and the protracted segments of constant middle frequency are found. (In joint research with A. B. Kogan Research Institute for Neurocybernetics of Rostov State University and with Texas Tech University, USA)
Neuron-neuron interactions in the molecular layer of frog cerebellum was studied by N. V. Samosudova and N. V. Larionova with techniques of electron microscopy and statistical processing. Changes of synaptic profiles in contacts of parallel fibres of granular cells on the Purkinje cells dendrites were found and their dependence was shown on the conditions for neuron operations (high mediator concentration, of glutamate and nitric oxide, in conjunction with different regimes of Purkinje cells stimulation). One could see the transition of straight form of contact into a convex one from bouton or spine side. Such changes are essential reflections of the neuron interactions.
The correlated study of ventilatory activity and behavioral manifestations is carried out by Yu. M. Burmistrov in freshwater crayfish, Procambarus cubensis, reared for many generations in aquaria and well adapted to laboratory conditions. A technique was elaborated, which is suitable for carrying repeated experiments on the same free-moving crayfish and for subsequent analysis of functional activity of the ventilatory pattern generator and its modifications caused by the effects of the higher nervous centres. The main conclusion is that the background locomotor activity, and especially the ventilatory activity are good indicators of crayfish functional state and its perceiving of external stimuli. It is possible that crayfish reactions to some unexpected changes of the environment which seem to be analogous with the orienting response of mammalians also include an emotional component, i.e. an individual estimation of the situation. (With Institute of High Nerve Activity of RAN.)
Dr. Z. Kh.-M. Khashaev studies the influence of the varied pharmacological media, especially the supertoxicants of the dioxin series, on the biomembrane penetrability. (In collaboration with the Institute of expermental and theoretical biophysics RAS (Poushchino), and Institute of biochemical physics RAS.)
Motor control.
The accuracy movements to the remembered targets were studying by M. B. Berkinblit and S. V. Adamovich. The subjects were old humans and targets were put in visual and kinesthetic forms. In contrast with young subjects the old ones show higher precision under kinesthetic presentation. One can think that they have difficulty with matching the target coordinates from space memory and coordinates of index finger given kinesthetically. Experiments on a deafferented patient were carried out in conditions of dark room and of structured visual field. After remembering of the target position the pointing followed with eye closed. In three-dimensional movements the main source of mistakes for the deafferented patient lied in the difficulty to control many joints and to allow gravity force. Showing in light room could not help in this problem and did not lead to diminishing of mistakes. Also a paradoxically more high exactitude of moving to the remembered target was revealed when the patient could see only tip of finger comparatively to the seeing of the whole arm. To study the difficulties of integration of afferentation in parkinsonics a new technique was worked out when the subject see his arm not in its real place. This produces a conflict between vision and proprioception. Variants of this technique were proposed for the rehabilitation of patients with motor insufficiencies. Also a 3-dimensional analysis was carried out of humans with parkinsonism (a special technique was created) and it was shown that using of some medicines (i.e. Pramipexole) diminishes their tremor. (In collaboration with Rutgers Univ., USA.)The study of the recurrent inhibition in the control motoneuron of rhythmic firing in human is carrying out by L. P. Kudina and N. M. Jukovskaya. It was analyzed the influence of the background frequency and arrive moment of the inhibition signal in the interimpulse interval under voluntary contraction. Crosscorrelative analysis of the impulse sequences of motoneuron pairs and analysis of the interspike interval duration have shown that the recurrent inhibition, faintly expressed in general, was more effective under lower background frequency and when the inhibition signal turns out at the end of the interspike interval. There were not explicit differences between the fast and slow muscles (flounder-like and biceps, correspondingly). (With the Bionic department of the Polish Institute of Biocybernetics and Medical Engineering.)
Bioinformatical principles. The method of the information structuring in scientific domains related to the study of the high neural activity and the complex approach to the data interpretation in the examination of retarded enfants, which were worked out by I. P. Lukashevich, permitted to create a neurological classification, to show the role of the right hemisphere in the speech, memory, and psychoemotional sphere development, and also to explain some pathogenetic mechanisms of disturbances in speech development and behavior in infants. The computer automatic diagnostic system "EEG-EXPERT" worked out on the base of the structure approach is using practically in a group of the research and medicine Moscow institutions. (With participation of the Institutes of Age Physiology and of Correctional Pedagogics, RA Education).
An analysis of the information interactions principles on the biological level is carried out by A. V. Chernavsky. (With the Sector 1.1 of the computer logic in the informational processes).
In the E. A. Liberman's group a preparative work carried out to an experiment for discovery of the consciousness processes in insects with help of accelerators generating mighty flood of neutrino.
Grants from:
Publications in 2000
Articles
In press
Conferences reports