1 PhD project in the IPP summer call 2018
Genes are not only translated into proteins, but gene products can also act on the level of RNA. These non-coding RNAs are classified into different classes: e.g. tRNA, snoRNA, piRNA, circular RNA, etc. One group, called long non-coding RNAs (lncRNAs) has been known for several decades and describes a very heterogeneous group which common feature is a length of >200 nt. With the advent of novel technological advances, the field has grown rapidly in the last decade. While there are more than 60,000 lncRNA mapped in mouse and human respectively, the functional characterization is lacking behind.
PhD Project: Characterization of long non-coding RNAs (lncRNAs) in embryonic stem cells
We have previously developed and applied techniques for the high throughput characterization of RNA and proteins, which we want to combine allowing systematic characterization of lncRNAs. In this project, you will combine state-of-the art systems level technologies (transcriptomics, quantitative proteomics, high content screening microscopy, CLIP-seq/RIP-seq, high through-put knock-down) to understand the functional consequences of lncRNA in mouse embryonic stem cells. This will include studying gene regulatory effects at the transcript level (next generation sequencing) and the protein level (mass spectrometry-based proteomics), investigating the localization by RNA-FISH (in combination with high content microscopy) and interactomics analysis. This will result in one of the largest functional lncRNA catalogue in embryonic stem cells.
This systematic study will be supplemented with mechanistic in-depth characterization of previously shortlisted lncRNA candidates important in ES cell maintenance and differentiation obtained from previous more targeted screens. We will study there effects by generating CRISPR knock-out lines of the respective lncRNAs and score them in specific assays to investigate the effect on ES cell maintenance and differentiation.
We are looking for a student with a master degree in Molecular Biology, Biochemistry or related fields. A strong motivation to work with diverse techniques and interest to apply them also in a screening setup together with interest in creation and analysis of large-scale data sets is required. You should show a high level of independence together with first class organizational and management skills. For each required technique support by experienced staff (either in the group or via the IMB Core Facilities) is available, thus prior knowledge with the technical aspects is not of immediate necessity and can be learned during the project.
Due to the collaborative nature of proteomics, the interest in collaborations beyond the direct research project is expected.
- Genome regulation by long noncoding RNAs. Rinn JL and Chang HY. Annu Rev Biochem. 2012; 81:145-66
- Combined RNAi and localization for functionally dissecting long noncoding RNAs. Chakraborty D, Kappei D, Theis M, Nitzsche A, Ding L, Paszkowski-Rogacz M, Surendranath V, Berger N, Schulz H, Saar K, Hubner N, Buchholz F. Nat Methods. 2012; 9:360-2
- Quantitative interaction screen of telomeric repeat-containing RNA reveals novel TERRA regulators. Scheibe M, Arnoult N, Kappei D, Buchholz F, Decottignies A, Butter F, Mann M. Genome Res. 2013; 23:2149-57
- The long noncoding RNA lncR492 inhibits neural differentiation of murine embryonic stem cells. Winzi M, Casas Vila N, Paszkowski-Rogacz M, Ding L, Noack S, Theis M, Butter F, Buchholz F. PLOS One. 2018; 13:e0191682
Dr Falk Butter
Phone: +49 (0)89-8578-2430