Division of Signaling and Functional Genomics

Prof. Dr. Michael Boutros

By silencing genes using RNAi we can analyse the genes’ effect in a quantitative and highthroughput manner. In this microscopy image of human cancer cells, nuclei are shown in red, cell membranes in green, and the cellular scaffolding in blue.
© dkfz.de

Cellular signaling networks control key decisions during development, health and disease. Genomic approaches such as whole genome sequencing and genetic mapping have identified many genetic variants in signaling components, yet their function and interactions oftentimes remain unknown. To address this, we perform systematic screens to functionally identify novel components, understand how they are connected and how to interfere with their aberrant regulation in disease. We use genetic and genomic methods to link genotypes to phenotypes, and cell biological approaches to study specific processes and probe underlying mechanisms. Current research interests are:

Systems genetics, chemical genetics and synthetic lethality in cancer cells:
Genetic variants can mask, alleviate or amplify the phenotypic effect of other variants; such genetic interactions can profoundly affect normal development and disease. We developed novel methods to identify genetic interactions in metazoan cells using RNAi and other perturbations. We computationally derived epistatic interactions to build models of cellular wiring under normal and disease conditions. Furthermore, we are interested in uncovering genetic dependencies in healthy and cancer cells by creating maps of complex genetic interactions. Building on this, we study genetic and chemico-genetic dependencies using single-cell, high content imaging and co-perturbations by RNAi and CRISPR/Cas9.

Wnt signaling networks in development and cancer:
Wnt signaling pathways are required for stem cell maintenance and patterning decisions in all metazoans and are often dysregulated in cancer. Recently, we discovered novel factors required for proper Wnt secretion and loading of Wnt family proteins onto extracellular vesicles. We use genetics in multiple model organisms (e.g. Drosophila and mouse) to understand the physiological and pathophysiological regulation of Wnt signaling. High-throughput screens and integrative genomic approaches are used to identify and characterize novel Wnt pathway components.

Experimental and computational approaches for high-throughput screening:
Our group pioneers novel methods for high-throughput functional screens using RNAi and CRISPR/Cas9. This includes the development of novel perturbation libraries, new image-based phenotyping assays and combinatorial approaches for genetic and small molecule perturbations. We also develop new computational tools for the analysis and visualization of high-throughput screens and integrative analysis of screening results, including algorithms and software applications to identify RNAi and CRISPR/Cas9 reagents and predict off-target effects.

Extensive interactions between different genetic alleles with large effects on many phenotypes have been documented in many model systems. Our research group is interested in the systematic analysis of genetic interactions to dissect genotype-phenotype relationships using single-cell and multi-omic approaches. We will develop genomic technologies required for high-throughput screening using genome engineering, cell-based screens in primary cell types and novel approaches for data integration. We aim to generate comprehensive functional maps of cellular processes in order to understand epistatic interaction in tumorigenesis and therapy response.
A second area of interest is the in-depth analysis of Wnt and interacting signaling networks in development, stem and tumor cells. We use a spectrum of model systems, from Drosophila to mouse and human cancer cells, to identify key components and understand how they are embedded into physiological processes.

For more information, visit the website of our division.


Prof. Dr. Michael Boutros
Signaling and Functional Genomics (B110)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 580
69120 Heidelberg
Tel: +49 6221 42 1951
Fax: +49 6221 42 1959

Selected Publications

  • Billmann, M. et al. (2017). Widespread Rewiring of Genetic Networks upon Cancer Signaling Pathway Activation. Cell Systems S2405-4712:30485-4.
  • Laufer, C. et al. (2013). Mapping of signaling networks through synthetic genetic interaction analysis by RNAi. Nat Methods, 10, 427–431.
  • Gross, J. C. et al. (2012). Active Wnt proteins are secreted on exosomes. Nat Cell Biol, 14, 1036–1045.
  • Bartscherer, K. et al. (2006). Secretion of Wnt ligands requires Evi, a conserved transmembrane protein. Cell, 125, 523–33.
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