Research Laboratory «Molecular Immunology»

Scientific results:

For the first time it has been found that microphages with OPA1 knockout, i. e. with mitochondrial dysfunction, demonstrate a significant increase in the level of p70S6K and p85S6K kinase phosphorylation and, therefore, mTORC1 activation. Moreover, it was found that mitochondrial dysfunction leads to an increase in mTORC1 activation in cells to a higher level in comparison with native cells.

We have assessed the impact of the found mechanism — mTORC1 over-activation in macrophages with mitochondrial dysfunction on polymerase activity. We found a significant increase in ribosomal biogenesis and rRNA/tRNA maturation in microphages with mitochondrial dysfunction, which confirms the increased activity of mTORC1 activation in these cells.

It has been found that mTORC1 activation leads to autophagy inhibition.

It has been discovered that activated immune cells rapidly change their biosynthetic and metabolic characteristics in immune response.

In accordance with these rearrangements mitochondria of immune cells also demonstrate flexibility and correct their bioenergy as well as metabolic properties. It has been found that the same processes occur during oncogenesis.

It has been found that the regulation of mTORC1, the key sensor and modulator of metabolism is disturbed as a result of immune cells activation.

It is supposed that there exists a connection of the mTORC1 — mitochondria complex, which is responsible for the activation of pathways that support the proliferation of tumor and immune cells.

Implementation of research results:

We have developed a technology for assessing mitochondrial metabolism in naive, pro-inflammatory and alternatively activated macrophages. We have established a connection between metabolic changes in cells and the activation of the mTORC1 molecular pathway.

The Laboratory has created a model of a hypothetical relation between metabolic rearrangements caused by mitochondrial dysfunction in human cells, and mTORC1 over-activation. It has been found that immune cells with defective mitochondria, with decreased respiration, are able to support a high level of mTORC1 activity and biosynthesis processes.

The area of use of said designs is the basic and applied research of carcinogenesis, mitochondrial metabolism, immunology as well as the development and implementation of new antitumor therapeutic strategies (by pharmaceutical companies, research and clinical centers).

Education and retraining of personnel:

• In 2021-2022 we conducted 5 internships of postgraduates at the leading scientist’s laboratory.

• In 2021 three members of our team completed an additional training course in biotechnology.

• In 2022 on the basis of the Laboratory the international conference «Symposium on the advances in cancer research in 2022» was staged that attracted 100 registered participants.

Collaboration:

University of Bern (Switzerland), University of Marburg (Germany), Moscow Institute of Physics and Technology (national research university), Kazan (Volga region) Federal University (Russia): joint research.