Details for Ellina Macaeva

Researchgroup Cell Systems & Imaging
Function Former member
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Publications http://lib.ugent.be/bibliografie/802001288015   
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Identification and functional analysis of biomarkers of low-dose (low-LET and high-LET) ionizing radiation

The problem of negative biological and health effects of low-dose ionizing radiation (IR) still remains the most serious, having not only biological, but also societal and economical importance as the effects of high doses of radiation are deterministic and well studied. But at the moment as a consequence of large-scale use of ionizing radiation in production sector, scientific research armament industry and medical diagnostics and radiotherapy (special interest in hadrontherapy), possible space flights to deep Space (e.g Mars mission) in the near future and accidents at nuclear power plants more and more people are exposed to low-dose radiation.

Taking into consideration all the above mentioned facts and the difficulty of getting epidemiological data for the doses lower that 0,5 Gy, the importance of study of this problem in laboratory conditions assumes even more relevance, as it is also makes it possible to reveal the molecular mechanisms of radiation damage.

The main goal of the project is to determine and to characterize the most suitable biomarkers for low-dose irradiation.

The main objectives of the project are the following:

  • To determine and to compare the effects of the same doses of high-LET (heavy ions) and low-LET (X-rays) IR using gene expression as biomarker.
  • To identify the new possible biomarkers for the exposure to low-doses of IR, to establish the functional basis and to understand the biological mechanisms of activation and regulation of these biomarkers.
  • To design a microarray chip suitable for a fast and simple analysis of a large cohort of individuals.

For our research we have chosen the peripheral blood mononuclear cells (PBMCs). PBMCs are almost an ideal model for this research because they are highly radiosensitive and can be used for cytokine secretion measuring and, consequently, for estimation of immunological response to irradiation.

The most appropriate biomarkers for high-LET and low-LET IR may differ. That is why our project foresees irradiation with low-doses of X-rays as well as heavy ions of different energies. After analyzing the data on gene expression variations for high-LET and low-LET radiation genes which are best suitable for radiation dose estimation will be chosen.

The new possible biomarkers of low-dose IR are the transcript variants and cytokines. Transcript variants analysis after irradiation will be performed using the DNA-microarrays. Cytokines secretion after irradiation will be measured using Luminex (multiplex array assay). Another very important point of the project is the functional characterization of new radiation biomarkers. For this, we intend to use the silencing approach (RNA interference). Other possible approaches are the use of inhibitors/activators, genetic induction (overexpression) , bioinformatics, etc.

The last objective is to design a microarray chip suitable for a fast and simple analysis of a large cohort of individuals. After analyzing the obtained information genes/transcript variants which are best suitable for radiation dose prediction will be chosen and a  library of corresponding ssDNA sequences will be designed and these probes will be spotted on glass slides.