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:
"Perturbation of the cellular nucleotide metabolism, especially inhibition of thymidylate synthase, has been applied in cancer treatment for decades. These drugs induce uracil incorporation into the genome leading to cell cycle arrest and eventually to programmed cell death [1]. In our research group, we used our uracil-DNA sensor constructs to detect genomic uracil in different experimental arrangements, like dot blot, immunocytochemistry, and DNA immunoprecipitation coupled sequencing (U-DNA-Seq) [2,3]. We have described genome-wide uracil patterns in drug treated HCT116 colon cancer cells that showed strong correlation with replication timing and chromatin state [3]. In the frame of the proposed PhD project, the candidate will further characterize these correlations with special focus on genomic features such as special chromatin structural elements, insulator segments, epigenetic profiles, CpG islands, repetitive elements, etc. First, this requires bioinformatic analysis of the already available U-DNA-Seq data, and exploring new correlating genomic features for which in cell and/or in vitro validation assays should also be performed. Hence, the ideal candidate should already have or acquire skills in bioinformatics (NGS, databases, scripting in R or python), in eukaryotic cellular studies (FISH, ICC, ChIP etc.), as well as in PCR-based in vitro methods. Knowledge in the field of cell biology, chromatin regulation, DNA repair and cellular signaling networks is also an advantage.
1. Wilson, P.M.; et al. Nat. Rev. Clin. Oncol. 2014, 11, 282–98
2. Róna, G.; et al. Nucleic Acids Res. 2016, 44, e28
3. Palinkas, H.L.; et al. Elife 2020, 9, e60498"
Number of students who can be accepted: 1
Deadline for application: 2024-05-30
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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