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Project title: Study of the role of cytokine genes and their regulatory epigenetic factors in the
development of asthma and COPD in East Kazakhstan
Call:
H2020
Project type:
RIA
Keywords:
asthma; COPD; molecular markers;
Main research areas:
molecular biology,genomics,identification of disease patterns
Short description:
In recent years, worldwide and in Kazakhstan, the number of patients with asthma and chronic
obstructive pulmonary disease (COPD) progressively increases. Genetic susceptibility and
environmental factors play important role in the development of asthma and COPD. In 80-90% of
cases the cause of COPD is tobacco smoking. The base of these diseases is a chronic inflammation of
the respiratory tract, which is caused by increased expression of a multiplicity of inflammatory
proteins.
An actual problem is the detection of molecular markers that allow to conduct of the differential
diagnosis between these diseases in patients older than 40 years. Moreover, of great interest is the
study of the role of environmental factors in the development of asthma and COPD. The increase of
spreading of asthma and COPD in the last decades, with a large divergence between populations and
differences in ethnic and racial groups living in different conditions, is an evidence of a significant
contribution of the environmental factors to the development of diseases. It is known that epigenetic
modulation, caused by environmental pollution, can alter the regulation of expression of genes that
play an important role in the pathogenesis of asthma and COPD.
Patients with asthma have increase of CD4 + T-lymphocytes in the airways, mainly T-helper 2 cells
(Th2), with the corresponding production of cytokines. In bronchial biopsies, small airways and lung
parenchyma of patients with COPD is detected infiltration by T cells (predominantly Th1 and
cytotoxic cells), increased numbers of neutrophils and macrophages. Epigenetic factors including
damage of DNA methylation, histone modifications change, specific expression of microRNAs and
other changes in chromatin organization may lead to reprogramming of the immune response - the
differentiation of naive T cells into effector various lines, especially in Th1- and Th2 cells, disruption
of the functioning of the dendritic cells, macrophage activation and damage airway epithelial barrier.
These changes may contribute to the formation of asthma and COPD.
Regions with a wide range of natural and man-made pollutant impacts on the environment provide
opportunities for epigenetic research. A large number of industrial factories in Kazakhstan have a
harmful impact on the environment and human health. One of these regions is Eastern Kazakhstan.
There are mining and processing of lead, zinc, copper, uranium and others. There is evidence of
exceeded indicators such as nitrogen dioxide, sulfur dioxide, formaldehyde, phenol. The greatest
threat for East Kazakhstan from the standpoint of environmental safety are the emission of industrial
gases and pollution of soil, including radiation.
In the planned study, markers of exposure to pollutants, polymorphic variants of genes, DNA
modification of histone proteins, the expression of specific miRNAs in immune cells will be studied in
LE14009
Kancelář podpory mezinárodního výzkumu a mobilit v Moravskoslezském kraji
a healthy population, patients with asthma and COPD. The study will include people who live in
disadvantaged environment and human settlements, free from pollution.
Partner profile sought:
We are looking for partners with experience and interest in the study of this problem. Partners can
come from different spheres: health, academic and research sector.
Required experience and skills of partners: knowledge and experience in molecular biology and
genomic studies of diseases, identification of disease patterns (SNPs, microRNA expression,
alterations in DNA methylation, histone modification).
Contact information:
Lukas Stranak
University of Ostrava
[email protected]
[email protected]
LE14009
Kancelář podpory mezinárodního výzkumu a mobilit v Moravskoslezském kraji