Sirkadiyen Ritmin Aşı ile Edinilen Bağışıklık Yanıtına Etkisinin Crıspr/Cas9 Tekniğiyle Araştırılması
Özet
Circadian rhythms are biological processes that occur through the
regulation of gene expression over time. These processes influence many biological
processes such as the sleep and wake cycle, hormonal release, metabolism and immune
functions. Circadian rhythms are therefore important for the regular expression of
genes and the proper regulation of the body. Since TIMELESS, a circadian gene, is
also involved in various biological processes such as cell cycle and DNA damage
response, it constitutes a broad research area. In this thesis, the relationship between
the TIMELESS circadian gene and the immune system was investigated. For this
purpose, firstly, the physicochemical properties, subcellular localization and 3D
protein structure of TIMELESS were examined using in silico methods. Then, the
evolutionary relationships of TIMELESS were determined by phylogenetic tree and
motif analysis. Then, 52 miRNAs targeting TIMELESS were identified by in silico
methods. These miRNAs were bioinformatically identified to be associated with
cancer, immunity and infection. In addition, using the CRISPR/Cas9 method, the
TIMELESS gene was knocked out in HEK293 cells and the expression levels of 84
innate and adaptive genes were examined by BCG vaccination. As a result of the
findings, it was determined that the TIMELESS gene is associated with immune
system functions. This thesis study may help to better understand the functions of the
TIMELESS gene and other circadian genes, to better investigate the effects of
circadian rhythms on health and disease, and to develop therapeutic approaches.
