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 Schick 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, 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 challenge is that the ARID subunits are enormous proteins with more than 1000 residues being intrinsically disordered. They are thus, difficult to study, and little is known about their regulatory functions. The Schick and Luck lab have developed jointly new computational and experimental techniques that enable the study of the ARID proteins in unprecedented ways.

PhD Project: Deciphering the disorder-mediated interactome of the BAF-associated ARID proteins with implications in colorectal cancer

In this primarily experimental project, the PhD candidate will apply novel NGS and structural proteomics techniques in combination with structure prediction tools such as AlphaFold and other in-house developed software, to discover direct interaction partners of the ARID proteins and dissect their interaction interfaces. We hypothesize that most regulatory and differential interaction partners between the ARID proteins that drive different phenotypes, are mediated by the disordered regions of the ARID proteins, which are poorly studied. In collaboration with the Schick lab, the PhD candidate will work with CRISPR-engineered cell lines to validate interaction interfaces and dissect the relevance of these novel interaction partners in mediating ARID subunit-specific functions in the context of DNA repair and cell cycle regulation. We are particularly interested in the relevance of these findings for colorectal cancer with possible further functional characterization in colon organoids. 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 Luck (BAF) as your group preference in the IPP application platform.

Publications relevant to this 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

Hubrich D, Alvarado Valverde J, Lee CY, Djokic M, Welzel M, Hintz K, Strom JM, Luck K (2026) Variant characterization in the intrinsically disordered human proteome. Nat Struct Mol Biol. 33(8):1183-1193 Link

Lee CY, Hubrich D, Varga JK, Schäfer C, Welzel M, Schumbera E, Djokic M, Strom JM, Schönfeld J, Geist JL, Polat F, Gibson TJ, Keller Valsecchi CI, Kumar M, Schueler-Furman O, Luck K (2024) Systematic discovery of protein interaction interfaces using AlphaFold and experimental validation. Mol Syst Biol, 20:75-97 Link

Strom JM, Luck K (2025) Bias in, bias out - AlphaFold-Multimer and the structural complexity of protein interfaces. Curr Opin Struct Biol. 91:103002 Link