Ruprecht-Karls-Universität Heidelberg
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Erhardt0120 - Scientist (f/m) / PhD position
Project no:
Erhardt0120

Project leader:

Project supervisor:
Erhardt, Sylvia
Application deadline:
31. Jul 2020
Start of PhD project:
1. Sep 2020

Project description:

Title:
Centromeric RNAs and their role in chromosome segregation
Summary:
Chromatin is commonly linked to the packaging material of every eukaryotic genome that safeguards and compacts DNA. Chromatin is, however, also the molecular macro-complex consisting of DNA, RNA, and protein, that regulates how and when the genome is made accessible for replication, segregation, or transcription.
These fundamental processes require massive restructuring of the chromatin and is controlled and regulated by highly specialized chromatin regions. Chromosome segregation, for instance, needs to be controlled carefully
by surveillance mechanisms to avert segregation defects, aneuploidy and resulting developmental defects or diseases such as cancer. This is mediated by the specialized chromatin region called the centromere. Centromeres do not rely on a specific DNA sequence for their spatial determination but rather on epigenetic mechanisms. The epigenetic determinants of centromeres include the centromere-specific histone variant CENP-A and non-coding RNAs. Even though CENP-A and non-coding RNAs from satellite repeats are vital, we still don’t fully understand the regulation of centromeres or the function of satellite repeats. It is, therefore, important to obtain a more detailed understanding of how centromeric proteins and RNA are interacting and responding to cellular stress, eventually leading to cellular responses that include cell cycle adaptation to the unfavourable conditions until the genome can safely be replicated, transcribed or segregated.

The project will explore how centromere-associated RNAs are involved in preventing or protecting cells from aneuploidy by sensing genome integrity during cell divisions at centromeres. More precisely, the projects explore how centromeric RNA and RNA-containing protein complexes regulate centromeric chromatin.
References:
Corless S, Höcker S, Erhardt S. Centromeric RNA and Its Function at and Beyond Centromeric Chromatin. (2020) J Mol Biol. doi:10.1016/j.jmb.2020.03.027

Pauleau A, Kajtez J, Bergner A, Erhardt S. Centromeric CENP-A loading requires accurate mitotic timing, which is linked to checkpoint proteins. (2019) PLoS Genet. doi: 10.1371/journal.pgen.1008380

Demirdizen E, Spiller-Becker M, Förtsch A, Wilhelm A, Bergner A, Bade D, Hessling B, Erhardt S. Localization of Drosophila CENP-A to non-centromeric sites depends on the NuRD complex. (2019) Nucleic Acids Res. doi: 10.1093/nar/gkz962.

Garcia del Arco A, Edgar BE, Erhardt S. Asymmetric CENP-A loading marks intestinal stem cells and reveals a non-mitotic function for CENP-A and its loading machinery. (2018) CellReports doi:10.1016/j.celrep.2018.01.079

Acharya S, Hartmann M, Erhardt S. Chromatin-associated noncoding RNAs in development and inheritance. (2017) Wiley Interdiscip Rev RNA. doi: 10.1002/wrna.1435.

Rošić S, Köhler F, Erhardt S. Repetitive centromeric satellite RNA is essential for kinetochore formation and cell division. (2014) J. Cell Biol. 10;207(3):335-49.
Methods that will be used:
Genetic manipulation of Drosophila melanogaster and human and Drosophila cells
Physiological analysis of phenotypes in Drosophila melanogaster
Biochemical analyses (immunoblot, immunoprecipitation, protein purification and binding assays)
Live and Fluorescence imaging techniques from light microscopy to super resolution microscopy
Cooperation partners:
Personal qualifications:
M.S. in Biochemistry, Molecular Biology, Cell biology, Genetics or related disciplines
Knowledge in microscopy, bioinformatics or Drosophila genetics is a plus.
Excellent previous academic performances
Good communications skills (English).
Strong interest in chromatin biology and epigenetics
Collaborative who enjoys being part of an international team.
Keywords: