Systematic investigation of the role of the BAF complexes in genome stability

1 PhD project offered in the IPP summer call Molecular Mechanisms in Genome Stability & Gene Regulation

Scientific Background

BAF chromatin remodellers are polymorphic complexes, subdivided into three major subtypes (cBAF, PBAF, GBAF) that regulate the accessibility of chromatin by sliding or ejecting nucleosomes. BAF complexes are primarily known for their role in gene regulation. However, there is increasing evidence that BAF complexes are also actively implicated in genome stability processes, especially those that involve DNA double-strand breaks (DSBs), in ways that are also likely independent from their chromatin remodelling functions. However, we know very little about the putative differential roles of individual BAF subunits and BAF subtypes in the protection and repair of DSBs, where in the genome DSBs occur upon BAF perturbation and how genome instabilities caused by BAF perturbations are linked to cancerogenesis. More than 20% of all cancers have a mutation in a gene encoding a BAF subunit.

PhD project: Systematic investigation of the role of the BAF complexes in genome stability

The PhD project is funded by a joint grant between the Luck and Schick lab from IMB as part of the second funding period of the CRC1361 on the regulation of DNA repair and genome stability. The grant aims to systematically investigate the role of BAF complexes in genome stability using a variety of techniques, including imaging-based screens, proteomics, genomics, CRISPR/Cas9 genome editing, functional assays and other molecular biology methods. The grant provides funding for a computational and an experimental PhD student, who will work closely together on the project. Here, we advertise for an experimental PhD position with the goal to obtain genome-wide views on the impact of BAF subunit perturbations on genome stability. To this end, the PhD candidate will use various next generation sequencing methods among which are state-of-the-art genomics approaches to map DNA lesions genome-wide. Integration of these with previously obtained results will enable generation of mechanistic hypotheses, which will be further investigated experimentally. Here, our goal is to focus on molecular mechanisms likely underlying tumor suppressive functions of BAF complexes.

We seek for a highly motivated, wet-lab experienced and science-enthusiastic PhD candidate who has a strong interest to approach scientific questions from a systems approach and in a collaborative team effort. The project is highly interdisciplinary and will be performed in close collaboration with the Luck lab, the core facilities from IMB and other groups of the CRC1361 (https://www.sfb1361.de). 

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

 

Publications relevant to the project

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

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

Contact Details

Dr Sandra Schick
Institute of Molecular Biology, IMB Mainz
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