Laboratory for Cell Physiology and Pathology

Scientific results:

We have determined the selectivity of lesions of regions of the brain in neurodegeneration and the relation with the difference in processes of education and energy consumption.

On the basis of a study of the fundamental mechanisms of neurodegenerative diseases, we have refined the methodological foundations of new strategies and methods of cell protection.

As part of the study of methods of the production of singlet oxygen during irradiation by laser at a wavelength of 1267 nm, we have determined the protective and restorative action on altered mitochondrial metabolism in neuronal cells with mutations related to different hereditary forms.

We have accumulated data on the overwhelming influence of singlet oxygen on pathological cells of the B16 line and the absence of negative impact on healthy fibroblasts.

It has been revealed that expression of FUS gene [1-359] in brain leads to mitochondrial dysfunction associated with inhibition of complex I of electron transport chain and with mitochondrial reactive oxygen species hyperproduction. The effect increases from the model of frontotemporal dementia to the model of amyotrophic lateral sclerosis differing in the level of FUS [1-359] gene expression.

A significant role of proteins from the synuclein family (alpha-, beta- and gamma-) in the regulation of intracellular redox balance between the production and neutralization of reactive oxygen species has been revealed. The most likely targets for these proteins are NADPH oxidases and monoamine oxidases, which play an important role in the physiology of brain cells. In addition, synucleins can affect the function of beta cells of the islets of Langerhans of the pancreas, and protein knockout leads to a deregulation of insulin secretion.

The possibilities of neuroprotection strategies based on the use of exogenous heat shock protein HSP70 or its regulator, erythropoietin, fragments of the protein glycation end product receptor, activators of transcription factor Nrf2, as well as a complex of physiologically active substances that have a positive effect on mitochondrial function have been studied.

It has been revealed that mutations of mitochondrial DNA localized in the genes of the subunits of complex I, complex III, as well as tRNA and rRNA, can have a significant effect both on the function of mitochondria and on processes in which mitochondrially encoded proteins are not directly involved. Changes in the mitochondrial genome lead to a decrease in ATP production, the effectiveness of oxidative phosphorylation, and the role of complex I in maintaining mitochondrial membrane potential. Despite the development of dysfunction in cells, the mechanisms of utilization of defective mitochondria (mitophagy) are disrupted. Various combinations of mtDNA mutations lead to multidirectional changes in the redox balance - from hyperproduction to a decrease in the formation of reactive oxygen species.

The mechanisms underlying the formation of a high level of autofluorescence in the blue-green part of the spectrum in cells with pathologies have been identified. It is shown that the most signal is associated with FAD, which is part of the complex II electron transport chain of mitochondria, as well as monoamine oxidases.

It has been shown that direct generation of singlet oxygen as a result of laser irradiation with a wavelength of 1267 nm can lead to an increase in the viability of brain cells in an in vitro model of beta-amyloid toxicity.

It was revealed that the cytoprotective effect of fumarate-containing drugs in acute hypoxia may be associated with the activation of endogenous protective mechanisms through the stabilization of HIF1a. This makes it possible to use such drugs during medical procedures with temporary tissue ischemia in order to reduce the likelihood of negative consequences in both the short and long term.

Implementation of research results:

The experimental methods used in a project have been incorporated into the educational programs at the bachelor's and master's levels "Biotechnical Systems and Technologies" and "Biotechnology", as well as in postgraduate program "Photonics, Instrumentation, Optical, and Biotechnical Systems and Technologies" 

Organizational and infrastructural changes:

During the implementation of the project, a Laboratory of Cell Physiology and Pathology was created and is constantly developing in the structure of the Research and Technological Center for Biomedical Photonics. Its material base allows for comprehensive studies of biological processes in vitro, ex vivo, in vivo. The laboratory made it possible to unite researchers from different departments of the university within one team (Institute of Instrumentation, Automation and Information Technology, Institute of Natural Sciences and Biotechnology, Medical Institute), as well as attract competent scientists from other Russian scientific organizations to solve actual problems in fundamental biology, as well as healthcare.

Education and personnel occupational retraining:

We have developed the basic professional education program (for highly qualified professionals training) in the direction 06.06.01 Biological sciences, major (profile) – Physiology.

We have developed additional education programs «Methods of working with cell cultures» (2021), «Confocal laser scanning microscopy in the practice of preclinical testing of pharmaceuticals» (2021), «Foundations of in vitro and ex vivo cell research» (2022), «Fundamentals of preclinical biomedical research» (2023).

Four dissertations for the degree of candidate of sciences and 1 dissertation for the degree of doctor of sciences have been defended.

Cooperation:

1. UCL, Great Britain
2. Aston University, Great Britain
3. University of Oulu, Finland
4. Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences
5. Institute of Cell Biophysics of the Russian Academy of Sciences
6. Federal State Autonomous Educational Institution of Higher Education «Belgorod National Research University»
7. National Research Lobachevsky State University of Nizhny Novgorod
8. Southern Federal University
9. Orel Regional Clinical Hospital
10. Research & Clinical Multifunctional Center of Medical Care for Mothers and Children, Orel
11. Saint Luca Clinical Hospital, Saint Petersburg