Of Mice and Men: Understanding The Regulation of Aging
We aim to understand the genetical program underlaying healthy aging in mice and man and try to find ncRNAs as biomarkers of aging. To achieve this we perform in-depth investigation of a huge collection of RNA-Seq data obtained from several tissues and ages of both species. Besides differential gene expression analysis of known mRNAs and ncRNAs, subsequent surveys like pathway analysis, gene expression clustering, chromosomal hotspot clustering, or SNP analysis are applied. We aim to identify and annotate novel genes involved in the processes of aging. This project is carried out in collaboration with the group of Prof. Dr. Witte of the Neurology Department of the University Hospital Jena.
The Role of MicroRNAs in Aging
In collaboration with the group of Alessandro Cellerino, the roles of miRNAs during aging of the short-living fish Nothobranchius furzeri are under investigation. Next-generation sequencing data of small RNAs of this fish from different tissues and different ages are analyzed to obtain a clear picture of the miRNA regulation. Furthermore, gene network analysis and comparative genomic conservation studies with other fish will be carried out computationally.
RNA:DNA Triplexes Involved in Aging
Recent studies suggested that some long non-coding RNAs (lncRNAs) can directly target DNA by forming RNA:DNA triple-helices (triplexes) or even G-quadruplexes (G4) at polypurine stretches. More interestingly, such sequence motifs are over-represented in promoter regions of proto-oncogenes (e.g. Myc and Kras), indicating that lncRNAs may be involved in the regulation and expression of cancer related genes. With this project we will decipher the epigenetic regulation by lncRNAs and triplexes and G4s in human and mouse cells that represent progressive states of breast cancer. Our investigations include deep sequencing of isolated DNA in order to uncover triplexes and G4s at oncogene promoters and other locations of the genome. With proteomic approaches we will reveal the epigenetic factors associated with triplexes and G4s to gain further insights of the mechanics of how these molecules influence chromatin structure.
Non-coding RNA Elements Causing X-linked Dystonia-Parkinsonism
We aim to take advantage of RNA-Seq in exploration of the ncRNAs involved in X-linked dystonia-parkinsonism (XDP), a hereditary progressive neurodegenerative movement disorder with features of dystonia and parkinsonism. Even after identifying the disease locus surrounding the TAF1 gene (a component of the transcriptional machinery) about 20 years ago, it is still not understood how exactly the improper sequence alterations lead to the formation of XDP. Since the sequence changes are located within untranslated regions of the genome, it is postulated that regulatory elements are affected leading to neuronal damage through dysregulation of gene transcription in the brain. By comparing patient and control transcriptome data we aim to identify the RNA elements unique to carriers of the XDP mutation and, furthermore, try to determine brain- and striatum-specific changes in the transcriptome diversity and abundance. The results of the bioinformatic computational analysis will be validated in the laboratory, using endogenous biomaterials.