Please contact Prof. A. Caflisch (email@example.com) if you are interested in a Master thesis in computational biochemistry.
We also offer Master theses in experimental biochemistry. As an example:
Drug Design for Epitranscriptomics Targets
Recent scientific breakthroughs have spawned a new area of epitranscriptomics, chemical modifications of RNA. One of the most common modification is N6-methyladenosine (m6A), which plays a crucial role in regulating transcriptomes and is therefore important in health and disease. The reader protein YTHDF2 specifically recognizes the m6A and regulates localization and stability of the bound mRNA. YTHDF2 is also involved in the development of acute myeloid leukemia and thus a promising anti-cancer target. This project includes expression (in E. coli) and purification of human YTHDF2. The purified protein will be used for solving the structure of complexes with small-molecule inhibitors identified in silico.
Assay Development for Epitranscriptomics-modulating Drugs
The finely organized network of gene expression is often perturbed in cancer and other genetic diseases. The recently discovered layer of RNA regulation based on co- and post-transcriptional RNA modifications gave rise to a new field named epitranscriptomics. While there are over 160 different RNA modifications discovered up to date, one of the most abundant modifications, N6-methyladenosine (m6A), is involved in most of the aspects of RNA regulation, i.e., splicing, nuclear export, stability, and translation initiation. Several m6A binding proteins have been identified differing in their intracellular localization and effect on RNA function. For example, METTL3 is a dual function protein, which acts as a methyltransferase in the nucleus in complex with METTL14 and other proteins, but switches its function to translation regulation when translocated to the cytoplasm. It has been associated with various cancers and comprises an attractive anticancer drug target. This project will focus on the establishment of a fast and reliable m6A quantification method, and verifying the established assay on METTL3-depleted cells via RNA interference. The developed assay will be further used to evaluate the efficacy of in-house METTL3 inhibitors.
In this project, you will learn the following cell and molecular biology techniques in a friendly and supportive environment:
mammalian cell culture
RNA interference (siRNA and plasmid transfection)
mRNA isolation using magnetic beads
RNA dot blot
target engagement assays (i.e., CETSA, InCell Pulse)