Over 200 specialized cells with diverse morphologies and functions exist in the human body, yet virtually every cell in the body contains the same genetic information. To exert cell-specific functions high fidelity mechanisms evolved to restrict the synthesis and processing of specialized regulatory RNAs. By using state-of-the-art deep sequencing technology and comparative genomics, our group investigates the epigenetic and transcriptional control of gene expression in mammalian cells. We have identified that transcription of coding and noncoding RNAs is entwined to ensure proper cellular function. This process is dynamic and tightly controlled when a cell is undergoing normal differentiation during development but gets unhinged upon transformation into cancer cells.
The research project of the student is embedded in the ongoing research activities of the group. It is designed to study the processes that regulate gene expression and processing of RNA molecules by combining computational and experimental techniques. In particular, the student will (i) perform transcriptomic analysis in liver cancer cells to identify cancer-driving abnormalities, (ii) study RNA signatures that are altered in cancer cells compared to normal cells to discover molecular differences and (iii) perform functional cell-based assays to understand the impact of these molecular differences in normal cell development.

The student will use techniques established in the group. Experimentally, the student will learn tissue culturing (hepatocytes and liver cancer cell lines), cell-based assays (cell viability, cell cycle arrest and kinase activity), basic molecular techniques (RNA isolation and common cloning techniques), loss- and gain-of-function experiments (siRNA, CRISPRi and CRISPRa), next generation sequencing (RNA library preparation and NextSeq 500 sequencing [our group shares the sequencing machine allowing fast sequencing turnover]). Computationally, the student will evoke command lines to assess sequencing quality (FastQC), align sequencing reads to the reference genome (Tophat2), count transcripts (HTSeq) and perform differential gene expression analysis (DESeq2). The techniques can be adjusted according to the student’s prior experience.

The research plan is based on experimental and computational research expertise in my laboratory and aligns well with the educational background of a master student. It involves understanding and gaining knowledge in the described research area, advancing of technical abilities and critical assessment of the research results in the scientific context. The project is designed to achieve completion within eight weeks. Jonas Sondergaard and Ionut Atanasoai (two highly experienced researchers in the Kutter lab) will support the supervision. This project is part of our research efforts in the lab and the successful contribution of the student will be acknowledged in the planned research publication.