Sector of mathematical modeling of radiation-induced effects
Research on the biological effect of high-energy heavy ions requires not only unique experimental facilities, but also a comprehensive theoretical assessment. A separate sector at the LRB is concerned with mathematical modeling problems. The Sector's main scientific activity is mathematical modeling of radiation-induced effects at the molecular and cellular levels. Through joint efforts of mathematicians, biophysicists, and computation specialists, a number of interdisciplinary theoretical studies are being performed focusing on the Monte Carlo modeling of energy deposition in charged particle tracks and calculation of molecular damage in the cell's sensitive structures — in particular, DNA damage. At higher levels of biological organization, the Sector does the analysis of the nonlinear dynamics of complex biochemical regulatory and repair systems and modeling neural network activity in the brain.
Main fields of research:
- Modeling energy deposition processes in charged particle tracks and mechanisms of biomolecule damage emergence induced by radiations with different characteristics;
- Development of mathematical models of the induction and repair of the key types of DNA damage in mammalian and human cells;
- Quantitative calculation of the mutagenic effect of ionizing radiations with different linear energy transfer;
- Modeling intra- and intercellular signal transport processes in the nervous system under exposure to ionizing radiations;
- Mathematical modeling of synaptic signal transfer disorders and synaptic plasticity disorders under exposure to ionizing radiations;
- Development of mathematical models of the functional activity of the neural systems of different parts of the brain under exposure to ionizing radiations.
The Sector's scientists did a series of studies on modeling the mutation process induced by radiations with different characteristics. In particular, a quantitative description was made of the whole complicated chain of molecular events: damage emergence, identification, and repair during the functioning of protein complex systems, including the formation of a mutation.
A calculation of the UV-induced mutation frequency in the uvrA and polA genes of E. coli bacterial cells with defects in the excision repair system , and in wild-type cells.
The action of accelerated heavy ions has its own specifics, which lead to the complex (clustered) damage of the DNA chain. The Sector's scientists perform calculations of energy deposition in heavy ion tracks and develop models of the emergence and repair pathways of such damage in mammalian and human cells.
A calculation of the repair kinetics of DNA double-strand breaks induced in human skin fibroblasts by different ionizing radiations at a dose of 1 Gy expressed as the number of γ-H2AX foci.
However, the most difficult and urgent problem of modern radiobiology — a challenge to theoreticians — is the just appeared issue of the mechanisms of the central nervous system disorders induced by ionizing radiations of different quality at the molecular and cellular levels.
A calculation of 500 MeV/nucleon 12C ion tracks in the pyramidal neuron of the CA1 region of the rat hippocampus (a) and the corresponding spatial energy distribution (b).
To solve the ultimate task, calculations are done of energy deposition in tracks hitting a population of nervous cells with complex morphology, and analyzed are the key types of radiation damage and disorders emerging in the functioning of ion channels and synapses at the isolated neuron level. But it is only the modeling of changes in the activity of neural networks of different parts of the brain that can clear up how these damage types and disorders will influence the cognitive functions. As the final result, such multi-level calculation scheme will allow evaluation of the probability of failures, for example, in different types of memory and learning, which has critical importance for space radiobiology.