Doctoral fellow – VIB-UGent Center for Medical Biotechnology
Principal Investigator: prof. Frank Peelman (PhD)
Tumor sequencing has led to a massive increase in data on somatic mutations. However, it also led to a significant amount of “variants of unknown significance”, for which little is known about their role in tumorigenesis.
Protein-protein interactions (PPIs) often determine how proteins exert their functions and play a key role in disease. Cancer drivers have a large number of protein interaction partners and their missense mutations tend to be enriched in PPI interfaces. Studying the effect of missense mutations in cancer drivers on their PPI and identifying the PPI interfaces can provide mechanistic insights into mutation-specific perturbations and their link to disease characteristics.
Deep mutational scanning (DMS) allows the high-throughput screening of all possible single amino acid substitutions in a protein of interest for a particular functional property. In this project, a new DMS method is being developed that combines random mutagenesis, MAPPIT, FACS and Illumina sequencing to delineate the different interaction interfaces of the cancer driver p53 with a large number of its protein interaction partners. Linking cancer-related phenotypes to the disruption of particular PPIs provides mechanistic insights into the consequences of specific mutations. In addition, the clinical outcome of variants of unknown significance may be inferred from variants of known significance within the same PPI interface. This could expand the use of genetic variants in diagnosis, prognosis and personalized medicine and thus increase the strength of genome sequencing in the clinic.
Stefanie Maes graduated in 2016 as a Master of Science in Biochemistry and Biotechnology.