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Transcriptional regulators of gene expression in human cells

Primary Supervisor: Dr Pawel Grzechnik, School of Biosciences

Secondary supervisor: Dr Saverio Brogna

PhD project title: Transcriptional regulators of gene expression in human cells

University of Registration: University of Birmingham

Project outline:

The aim of the project is to uncover novel roles for transcriptional factors and to investigate how mRNA synthesis alters gene expression in human cells.

Precise control of transcription and RNA processing is essential for gene expression regulation in all eukaryotic organisms. Deregulation of these processes can lead to pathological outcomes including accelerated ageing and carcinogenesis. Human RPRD (Regulation of Nuclear mRNA Domain-Containing) proteins, are putative new players in mRNA synthesis, important for the regulation of gene expression.

The member of the RPRD family, CREPT protein (cell cycle-related and expression-elevated protein in tumour) interacts with RNA Polymerase II and is present at 5’ and 3’ regions of selected protein-coding genes. The 5’-end recruitment to the transcribing complex has been recently attributed to the role of CREPT in Pol II CTD acetylation which facilitates transcription elongation. However, functions of CRPT and other RPRD proteins in RNA biogenesis remain largely uncovered.

Therefore, the aim of this project is to investigate roles for RPRD proteins in mRNA synthesis with a special focus on transcription elongation and termination. The outcome of this research will help to better understand how gene expression is regulated in eukaryotic cells.

BBSRC Strategic Research Priority: Integrated Understanding of Health: Ageing

Techniques that will be undertaken during the project:

  • Genome editing (CRISPR-Cas9)
  • Illumina RNA sequencing approaches: (RNA-seq, 4sU-RNA-seq, DRB-RNA-seq)
  • Chromatin immunoprecipitation (ChIP-seq)
  • Nanopore RNA sequencing (direct RNA-seq)
  • Western Blotting
  • Real-time PCR (qPCR)
  • Immunofluorescent microscopy
  • Standard molecular biology techniques

Contact: Dr Pawel Grzechnik, University of Birmingham