Genome-regulation by chromatin remodeling

1 PhD project offered in the IPP winter call 2020/2021

Scientific Background

Genomic DNA is highly compacted into chromatin in order to fit into the nucleus of a cell. The packaging further provides a regulatory layer for DNA accessibility and therefore all DNA-dependent processes, such as transcription, DNA repair or replication. ATP-dependent chromatin remodelers can modulate the accessibility by moving or evicting nucleosomes. One class of these remodelers are the BAF complexes, very large multi-protein complexes existing in many different configurations in human cells. Their importance is highlighted by the fact that mutations in genes coding for these complexes are found in more than 20% of all human cancers and also in developmental diseases. The molecular consequences of these mutations are hardly known so far. Thus, understanding the cellular pathways in which the diverse BAF complexes are involved is crucial towards understanding the misregulations causing the diseases.

PhD Project:

BAF chromatin remodelers can theoretically be composed in several hundreds of distinct complexes likely contributing to their role in many different cellular processes. We are far from a comprehensive understanding in which processes individual complexes play a role and how this specificity is reached. In this project, we aim to systematically investigate this in cell culture models by using state of the art technologies, including proteomics, genomics, molecular biology, CRISPR/Cas9, screening, imaging as well as various functional assays. 

We therefore seek for a highly motivated, wet-lab experienced and science-enthusiastic PhD candidate that has a strong interest to approach scientific questions from a systems approach, but further enjoys unraveling the mechanism behind. The project is highly interdisciplinary and will be performed in close collaboration with Katja Luck as well as the core facilities from IMB.

Relevant publications:

Schick S, Rendeiro AF, Runggatscher K, Ringler A, Boidol B, Hinkel M, Májek P, Vulliard L, Penz T, Parapatics K, Schmidl C, Menche J, Boehmelt G, Petronczki M,  Mueller AC, Bock C and Kubicek S. (2019). Systematic characterization of BAF mutations provides insights into explains intra-complex synthetic lethalities in human cancers. Nature Genetics, doi: 10.1038/s41588-019-0477-9.

Contact Details:

Dr Sandra Schick