Projects Offered

1 PhD project offered in the IPP winter call 2026/2027

Scientific Background

Transcription, replication and DNA repair represent key processes that act on DNA to ensure cell survival. As DNA is packaged into chromatin, chromatin remodeling, for example by BAF complexes, is required to coordinate and support genome maintenance processes. The BAF complexes exist in three different subtypes, each composed of multiple subunits. In previous work by us in collaboration with the Luck lab (IMB), we found that loss of either of the three BAF subtype-determining ARID subunits results in distinct vulnerabilities and resistances upon treatment with genotoxic or cell cycle-inhibiting agents. Since mutation of the ARID subunits is frequently associated with cancer, including colorectal cancer, we believe that these phenotypes are relevant to dissect molecular and cellular functions of the ARIDs and understand mechanisms that drive disease upon ARID perturbation. The Schick and Luck lab have developed jointly new computational and experimental techniques that enable the study of the ARID proteins in unprecedented ways.-mutated diseases.

PhD project: Deciphering the role of the BAF-associated ARID proteins in DNA mismatch repair and cell cycle control in colorectal cancer

ARID mutations in colorectal cancer are associated with microsatellite instability (MSI), usually caused by defective mismatch repair (MMR). We further observed MMR proteins in proximity to ARID1A. We thus want to use CRISPR engineered cancer cell lines and colon organoids to study the connection between ARIDs and MMR using compound screening and assessing the impact of ARID subunit loss on MSI and vice versa. In addition, we want to understand the impact of ARID mutations on cell cycle regulation in a cell type- and ARID-dependent manner. 

In this project, the PhD candidate will apply bulk and single cell NGS and proteomics techniques in combination with genome engineering, compound screening and microscopy approaches using cell culture models, including colon organoid cultures. This project will be performed in collaboration with the Luck lab, who will complement this project by a structural proteomics approach. This project is embedded within the collaborative research consortium SFB1361 (www.sfb1361.de, pending funding decision in November 2026).

If you are interested in this project, please select Schick (BAF) as your group preference in the IPP application platform.

Publications relevant to the project

Spang K, Barry C, Ntasiou C, Aretaki E, Wolf M, Schumbera E, Kielisch F, Bonn L, Welzel M, Rühle F, Schäfer C, Luck K, Schick S (2026) Systematic drug profiling across BAF complex perturbations reveals distinct dependencies. bioRxivLink

Varga J, Kube M; Luck K, Schick S (2021) The BAF chromatin remodeling complexes: structure, function, and synthetic lethalities. Biochem Soc Trans 49 (4): 1489-1503 Link

Schick S*, Grosche S*, Kohl KE*, Drpic D, Jaeger MG, Marella NC, Imrichova H, Lin JMG, Hofstätter G, Schuster M, Rendeiro AF, Koren A, Petronczki M, Bock C, Müller AC, Winter GE, Kubicek S (2021) Acute BAF perturbation causes immediate changes in chromatin accessibility.Nature Genetics 53: 269-278 Link (*indicates joint contribution)

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, Pentronczki M, Müller AC, Bock C, Kubicek S (2019) Systematic characterization of BAF mutations provides insights into intracomplex synthetic lethalities in human cancers.Nature Genetics 51: 1399-1410 Link