Whereas accurate maps exist depicting biochemical pathways, equivalent charts do not exist for the genetic wiring of human cells. This lack of knowledge provides a rich ground for biological discovery. Our goal is to create genetic tools for human cells and to apply these to address important biological questions. Specifically, we use haploid human cells as a genetic model system and apply insertional mutagenesis to link genes to phenotypes (Brockmann et al, 2017). In the last years we have used this approach to find host factors for pathogens (Staring et al, 2017), to identify essential genes and synthetic lethal interactions (Blomen et al, 2015), and to search for new genes relevant for immunotherapy (Mezzadra et al, 2017).
Currently we are using genetics in haploid human cells to discover missing enzymes in key cellular processes (Nieuwenhuis et al, 2017; Landskron et al, 2022) and to elucidate new signaling or metabolic pathways that may play a role in cancer. Integrated analysis of our growing genotype-phenotype database sheds light on the genetic regulatory mechanisms that control human cells.
Brockmann et al 2017-Nature 546, 307-311; Staring et al 2017-Nature 541, 412-416; Blomen et al 2015-Science 6264, 1092-96; Mezzadra et al 2017-Nature 549, 106-110; Nieuwenhuis et al, 2017-Science 6369, 1453-1456; Landskron et al 2022-Science 6595, DOI: 10.1126/science.abn60.