Thesis supervisor: Angéla Békési
Location of studies (in Hungarian): Hun-Ren Research Center for Natural Sciences, Institute of Molecular Physiology, Genome Metabolism Research Group Abbreviation of location of studies: H-REN
Description of the research topic:
Thymidylate synthase (TS) inhibitory anticancer drugs induce uracil incorporation into the genome leading to cell cycle arrest and programmed cell death (PMID: 24732946). In our research group, we developed uracil-DNA sensors to detect genomic uracil in different experimental arrangements including DNA immunoprecipitation coupled sequencing (U-DNA-Seq, PMID: 26429970). We have described genome-wide uracil patterns in HCT116 colon cancer cell lines treated by TS inhibitors (PMID: 32956035). Meanwhile, we also have results on drug induced mutagenicity, and uracils in ssDNA context and whole transcriptome sequencing data were also obtained for this model system. In the frame of the proposed PhD project, the candidate will address the correlation between genomic uracil and the transcription regulation assuming that incorporated uracil might affect transcription activity in different ways. First, he/she will refine the bioinformatic analysis of different sequencing data, then match these with replication timing and other genomic profiles to perform a multidimensional correlation analysis using machine learning algorithms. We aimed at identifying groups of genes showing different types of correlation between uracil and transcription. The transcriptional change and the uracil results will be validated by PCR based techniques and cellular staining methods. Then, by promoter analysis, uracil sensitive transcription factors should also be identified and tested in vitro for their binding specificity. Hence, the ideal candidate should already have or acquire skills in bioinformatics as well as in eukaryotic cellular studies and PCR-based in vitro methods.
Required language skills: English Further requirements: Skills in bioinformatics, NGS data processing, learning algorithms are required, and experiences with cellular and molecular techniques are also useful.
Number of students who can be accepted: 1
Deadline for application: 2024-05-31
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
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