The coming of recombinant DNA technologies in the 1970s initiated  a new understanding of cellular processes and genetic diseases. However, limited applicability in primary cells and whole organisms trapped researchers as readers and not writers of genetic processes.

The recent discovery and application of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 system as a potent method of inducing targeted DNA breaks opened unprecedented venues in the field of genome engineering. From inactivating genes, to correcting mutations, to deleting, inverting, and translocating large chromosomal fragments, CRISPR-Cas9 technology has even expanded towards whole-transcriptome and -epigenome control. Through these methods, integrated approaches now allow the precise recapitulation of complex genetic diseases, and subsequent probing for their weaknesses.

With the assumption that a comprehensive understanding is the crucial basis for finding a cure, we apply multiplexed CRISPR-Cas9 genome engineering to model the genetic landscape of leukemia. Major efforts in cancer genome sequencing have yielded deep insights both into the overall mutation burden and the sequence of acquisition. However, the mechanisms through which diverse mutational patterns orchestrate leukemic transformation remain elusive. Thus, tackling these open questions with in vitro and in vivo based CRISPR-Cas9 cooperation screens is the focus of several projects. In combination with whole-transcriptome analyses and synthetic-lethality drop-out screens, these studies will advance our understanding of the genetic interplay in leukemia towards better treatment options.