Doctoral study program: Life Sciences

Supervisor: Dr. Dalibor Blazek, PhD.

Topic title: Mechanistic Roles of Cyclin-Dependent Kinase 12 (CDK12) in Transcription Regulation and Cancer Biology.

Annotation:

CDK12 is a transcriptional cyclin-dependent kinase (CDK) found mutated in various cancers. In previous studies, we found that CDK12 maintains genome stability via optimal transcription of key homologous recombination repair pathway genes, including BRCA1, and plays a role in cell cycle progression by regulating processivity of RNA Polymerase IIat core DNA replication genes. Apart from the C-terminal domain of RNA Polymerase II, other cellular substrates of CDK12 are not known. In this research, we propose using a screen in cells carrying an analogsensitive mutant of CDK12 to discover its novel cellular substrates. The substrates and their roles in normal and cancerous cells will be characterized by advanced techniques of molecular biology and biochemistry.

Recommended literature:

1. Pilarova K, Herudek J, Blazek D.*: CDK12: Cellular functions and therapeutic potential of versatile player in cancer: Nucleic Acids Research Cancer (Oxford University Press) k2 (1): zcaa003 (2020)
2. Chirackal Manavalan A.P., Pilarova K., Kluge M., Bartholomeeusen K., Oppelt J., Khirsariya P., Paruch K., Krejci L., Friedel C.C., Blazek D* : CDK12 controls G1/S progression via regulating RNAPII processivity at core DNA replication genes. EMВО reports 20(9):47592 (2019)
3. Ekumi KM, Paculova H, Lenasi T, Pospichalova V, Bösken CA, Rybarikova J, Bryja V, Geyer M, Blazek D*, Barboric M*. Ovarian carcinoma CDK12 mutations misregulate expression of DNA repair genes via deficient formation and function of the Cdk12/CycK complex. Nucleic Acids Research 43(5):2575-89 (2015)
4. Bösken CA, Farnung L, Hintermair C, Merzel Schachter M, Vogel-Bachmayr K, Blazek D, Anand K, Fisher RP, Eick D, Geyer M. The structure and substrate specificity of human Cdk12/Cyclin K. Nature Communications 5 (2014).

Research area: Cancer biology, RNA/nucleic acids health research, correlative approaches in microscopy, Proteomics, Genomics, Chemical Biology.

Keywords: CDK12, transcription, mRNA processing, RNA polymerase II, cancer, genomics, proteomics, substrates, kinase inhibitors.

Funding of the PhD candidate:

Project EXPRO (2023-2027)
In the academic year 2026/27 the net income of the CEITEC PhD School student is expected to be at least CZK 29,400 (approx. EUR 1215)

Requirements for candidate:

Background in molecular biology, biochemistry, or life sciences. Interest in bioinformatics and data analysis is desirable.

Information about the supervisor:

2 PhD students
2 absolvents

Supervisor´s personal webpage https://www.ceitec.eu/dalibor-blazek-ph-d/u25918
Research group info https://www.ceitec.eu/inherited-diseases-transcriptional-regulation/rg38

Start date: September 2026

Sign-up link:https://www.ceitec.eu/mechanistic-roles-of-cyclin-dependent-kinase-12-cdk12-in-transcription-regulation-and-cancer-biology/t11643