Thesis supervisor: Angéla Békési
Location of studies (in Hungarian): BME Alkalmazott Biotechnológia és Élelmiszertudományi Tanszék Abbreviation of location of studies: BME
Description of the research topic:
Uracil in DNA is considered as a damage to be repaired, however, emerging evidences suggest its possible functions in some cases (immunity [1,2], developmental processes [3-5]). Most recently, we found elevated genomic uracil content in Zebra fish embryos prior to the activation of the zygotic transcription. Incorporated uracil might affect transcription either negatively by interfering with transcription factor binding [6], or RNA polymerase activity [8], or positively upon uracil-DNA processing, when nicks in the promoters might help unwrapping DNA [7]. We established a model system of HCT116 colon cancer cell lines with altered DNA repair capacities. Using our uracil-DNA sensors [9] in U-DNA-Seq, we determined drug induced genomic uracil patterns that correlated with replication timing and active euchromatin [10]. We obtained whole transcriptome data also. In the proposed PhD project, the candidate will analyze the correlation between genomic uracilation and transcription and identify groups of genes with positive or negative correlations as well as uracil sensitive transcription factors. For validation, cellular staining, PCR based techniques, and protein-DNA binding assays will be used. The ideal candidate acquires skills in these methods as well as in bioinformatics (NGS, scripting, machine learning approaches). (Ref PMIDs.: [1] 24920531, [2] 27585283, [3] 14996835, [4] 22685418, [5] 23238493, [6] 12069602, [7] 30445637, [8] 30892639, [9] 26429970, [10] 32956035)
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