Rolf Backofen & Tanja Vogel

Determination and functional characterisation of non-coding RNA in FOXG1-dependent forebrain development and Rett syndrome



Prof. Dr. Tanja Vogel

Institute for Anatomy and Cell Biology Dept. Molecular Embryolog

Albert-Ludwigs-University of Freiburg
Albertstr. 17 79104 Freiburg (Germany)

Phone : +49 (0)761 203 5086
Fax : +49 (0)761 203 5091

E-Mail : tanja.vogel@anat.uni-freiburg.de

Web : See online here



Prof. Dr. Rolf Backofen

Institute for InformaticsDept. of Computer Science

Albert-Ludwigs-University of Freiburg
Georges-Koehler-Allee 106 79110 Freiburg (Germany)

Phone : +49 (0)761 203 7461
Fax : +49 (0)761 203 7462

E-Mail : backofen@informatik.uni-freiburg.de

Web : See online here

Rett syndrome is a neurodevelopment disorder with symptoms like progressive loss of cognitive capabilities, spastic paralysis, ataxia and epilepsy. Rett syndrome is classified under autism spectrum disorder (ASD). Classical Rett syndrome cases (~90%) are ascribed to MECP2 mutations, but FOXG1 haploinsufficiency results in similar phenotypes. Hence, the latter is called as atypical Rett or Rett-like syndrome. Recent studies suggest that expression of non-coding RNAs (ncRNA) is regulated by MECP2 as well as by FOXG1 and that the loss of this regulation may have an important role in disease progression. Molecular similarities between MECP2- and FOXG1-mediated Rett syndromes are yet to be deciphered. Therefore, in this project, we aim to systematically analyse the molecular parallels between loss of MECP2 and FOXG1 in the forebrain of mice with a special emphasis on ncRNAs (lncRNAs and miRNAs). MECP2- and FOXG1-deficient FOXG1 expressing cells will be generated to elucidate their functions in regulation of ncRNA biogenesis as well as in nervous system development and adulthood using parallel high throughput sequencing approaches. Further, to perform lncRNA and miRNA target predictions, as well as prediction and validation of transcriptional and post-transcriptional regulatory mechanisms, we intend to use interdisciplinary approaches involving the fields of bioinformatics, molecular biology, and biochemistry. The interplay of lncRNA and RNA-binding proteins (RBP) such as Polycomb members and other histone modifiers using RBP-CLIP and the interactions of ncRNA with either RNA and/or DNA will be studied in detail. To reveal the functional roles of ncRNAs during neurodevelopment and Rett syndrome, using loss and gain of function strategy, we will then study the effects on different pathways governing the most critical processes such as proliferation, survival and differentiation of neural stem cells/progenitors. The advantage of using different Rett syndrome mice models is that it not only allows us to understand the epigenetic roles of MECP2 and FOXG1 and the affected molecular pathways in Rett syndrome but also provides common targets that have therapeutic importance.

Key Technologies used in Prof. Tanja Vogel’s lab:

The following are some of the key technologies that are routinely used in Prof. Vogel’s lab:

1. Co-ImmunoPrecipitation (Co-IP) Assay,
2. CrossLinking ImmunoPrecipitation (CLIP) assay,
3. DNA methylation assay (Bisulfite conversion method),
4. Proximity Ligation Assay (PLA),
5. Chromatin ImmunoPrecipitation (ChIP) assay,
6. Real Time Cell Analyses (RTCA), and
7. Enzyme Linked ImmunoSorbent Assay (ELISA).

Key Technologies used in Prof. Backofen’s lab:

We provide expertise for high-throughput data analysis (RNA-seq, ChIP-seq, CLIP-seq, Methyl-seq) as well as user support through the Galaxy platform. Furthermore, we provide tools for RNA secondary structure prediction, RNA-protein interaction prediction, RNA-RNA interaction prediction and small ncRNA functional annotation.

Last Publications

Recent publications from Prof. Tanja Vogel’s lab:

- Nicole Hellbach et al. Neural deletion of Tgfbr2 impairs angiogenesis through an altered secretome. Human Molecular Genetics, 2014 Dec 1;23(23):6177-90.

- Shalaka Wahane et al. PI3K-p110-alpha-subtype signalling mediates survival, proliferation and neurogenesis of cortical progenitor cells via activation of mTORC2. Journal of Neurochemistry, 2014 Jul;130(2):255-67.

- Rolf Backofen and Tanja Vogel. Biological and bioinformatical approaches to study crosstalk of long-non-coding RNAs and chromatin-modifying proteins. Cell and Tissue Research, 2014 Jun;356(3):507-26.

- Oleksandra Karpiuk et al. The Histone H2B monoubiquitination regulatory pathway is required for differentiation of multipotent stem cells. Molecular Cell, 2012 Jun 8;46(5):705-13.

- Nicole Büttner et al. Af9/Mllt3 interferes with Tbr1 expression through epigenetic modification of histone H3K79 during development of the cerebral cortex. Proceedings of the National Academy of Sciences USA, 2010 Apr 13;107(15):7042-7.

Recent publications from Prof. Rolf Backofen’s lab:

- Ilik IA, Quinn JJ, Georgiev P, Tavares-Cadete F, Maticzka D, Toscano S, Wan Y, Spitale RC, Luscombe N, Backofen R, Chang HY, Akhtar A. Tandem Stem-Loops in roX RNAs Act Together to Mediate X Chromosome Dosage Compensation in Drosophila. Molecular Cell. 2013;51(2):156–73.

- Wright PR, Richter AS, Papenfort K, Mann M, Vogel J, Hess WR, Backofen R*, Georg J*. Comparative genomics boosts target prediction for bacterial small RNAs. Proc Natl Acad Sci USA. 2013. (* joint corresponding author)

- Lange SJ, Maticzka D, Mohl M, Gagnon JN, Brown CM, and Backofen R: Global or local? Predicting secondary structure and accessibility in mRNAs. Nucleic acids research 40, 5215-5226 (2012).

- Maticzka D, Lange SJ, Costa F, and Backofen R: GraphProt: modeling binding preferences of RNA-binding proteins. Genome biology 15, R17 (2014).

- Pavankumar Videm, Dominic Rose, Fabrizio Costa, and Rolf Backofen: BlockClust: efficient clustering and classification of non-coding RNAs from short read RNA-seq profiles. Bioinformatics, 30 no. 12 pp. i274-i282, 2014.

People Images