Team:MEPhI/Description

Project Description

To date, several hundred low-molecular compounds with radioprotective properties have been described, but all these substances have a number of significant drawbacks:

  1. Capable of protecting against only one type of damage caused by radiation
  2. Have a short period of exposure to the body
  3. Have many side effects harmful to health

We have set an ambitious task to overcome the existing limitations of radioprotectors by using natural radiation protection mechanisms based on biological macromolecules that are as safe as possible for humans. As the main reference point for determining the properties of our radioprotectors, we used those characteristics that are necessary for long-term human protection during space travel beyond the earth's magnetosphere.

The creation of biological protection against chronic radiation exposure in space is a complex technological task to solve, so it was necessary to go through several stages:

  1. Make sure that effective natural mechanisms of protection against chronic radiation exist, not only in invertebrates (such as tardigrades) but also in mammals, including humans.
  2. Сhoose proteins and RNA that can effectively protect a person from ionizing radiation
  3. Сhoose the method of delivery of biological macromolecules to the human body
  4. Select a genetic vector capable of producing proteins and RNA in sufficient quantities
  5. Provide the ability to adjust the radioprotective function
  6. Ensure the safe disposal of the carrier of radioprotective genetic information

Experimental work plan:

  1. Make sure that there is a mechanism of radiation hormesis in humans.
    2. At this stage, we had to establish that there are grounds for searching for radioprotective proteins and RNA in humans. To do this, it was necessary to analyze the scientific literature in order to understand how prolonged exposure to ionizing radiation affects human health. It turned out that many publications indicate that people can adapt to chronic radiation exposure. For example, people who live for a long time in conditions of increased background radiation do not have an increase in the number of diseases associated with radiation exposure, compared with those of people who are not exposed to chronic radiation (DOI:10.1177/1559325815592391).

  2. Selection of RNA and proteins capable of performing a radioprotective function.
    3. To solve this problem, we analyzed databases containing information about the transcriptome of people living in regions with high levels of natural radiation exposure (dose load per person over 15 mGr per year). We also analyzed the available scientific literature on this topic (for example, a total of 9 targets were selected for testing in genetic constructs, some of which are homologous to the genes of tardigrades, allowing them to exist at very high levels of radiation fatal to humans.

  3. The main requirement for the means of delivery that we have identified is human safety.
    4. To avoid interference with the human genome and to produce radioprotective molecules, we decided to modify the genome of bacteria that are typical for the intestines of a healthy person. We plan to make radioprotective bacteria convenient for use, so in our experiments, we use two approaches: the first is to use probiotic bacteria of the species Bifidobacterium bifidum and Lactobacillus Plantarum, capable of being in the intestine only for a short time. The second approach is to use a typical intestinal strain of E. coli capable of penetrating the intestinal biofilm and staying there for several months.

    In order to avoid the loss of the radioprotective plasmid in the process of bacterial reproduction, we introduced a special insertion (partition locus) into the genetic vector, which guarantees the inheritance of the radioprotective plasmid.

    To make the production of a radioprotector manageable, we also added an inducible promoter to the genetic vector, which triggers the production of a radioprotector only in response to an external chemical stimulus, which is a disaccharide molecule that is rarely found in food.

    Before testing our system on living organisms, we modeled an artificial system based on the Transwell system in which human cells and bacteria are exposed to prolonged irradiation under controlled conditions.

    As soon as we understand which of the RNA and protein molecules we have chosen can be used to most effectively protect human cells from radiation, we will take the next step and try to protect laboratory mice from radiation using radiation parameters that do not pose a threat to their lives.