Primary Supervisor: Dr Pawel Grzechnik, School of Biosciences

Secondary supervisor: Dr Matthias Soller

PhD project title: Transcriptional regulators in human cells

University of Registration: University of Birmingham

Project outline:

The aim of the project is to investigate how factors involved in mRNA synthesis alters gene expression in human cells.

Precise control of transcription and RNA processing is essential for correct regulation of gene expression in all eukaryotic organisms. Transcriptional deregulation can lead to pathological outcomes including accelerated ageing and carcinogenesis.

A successful candidate will study functions of human RPRD (Regulation of Nuclear mRNA Domain-Containing) proteins and will identify roles of CREPT (Cell cycle-Related and expression-Elevated Protein in Tumour, RPRD1B) in transcription. RPRD1B/CREPT is overexpressed in ~80% of tumours, interacts with RNA Polymerase II and is present on actively transcribed genes. Depletion of RPRD1B/CREPT results in accumulation of RNA:DNA hybrids (R loops) and increased DNA damage.

Therefore, the aim of this project is to investigate roles for RPRD proteins in mRNA synthesis with a special focus on RPRD1B/CREPT function in 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)I
• Immunofluorescent microscopy
• Standard molecular biology techniques

Contact: Dr Pawel Grzechnik, University of Birmingham