Helmholtz University Young Investigators Group Bioinformatics & Transcriptomics
The Young Investigators Group aims at unraveling disease-relevant differentiation processes of immune cells. We focus on the role of ncRNAs - transcripts which are produced from the allegedly non-informative, non-protein coding part that makes up for most of the human genome. We use bioinformatic and experimental approaches to obtain a systems biologic understanding how ncRNAs contribute to reflecting environmental influences at the regulatory layer of epigenetics, which is particularly relevant for differentiation processes.
Recent transcriptomics studies have shown that about 70 - 90 % of the human genome is transcribed into RNA on at least one strand. However, only roughly 2% of the genome code for proteins, i.e. the majority of transcripts a human cell is capable of producing are non-protein coding (ncRNAs). While the number of protein coding genes remains nearly constant, the non-protein coding fraction of genomes increases strongly with organism complexity in animals, suggesting a role of non-coding elements in evolution of complexity.
NcRNAs show highly specific expression patterns, which are more context specific, i.e. dependent on cell type or state than for mRNAs. Also, ncRNAs are frequently disease associated, making them interesting candidates for biomarker development and for analyzing their functional role in disease. While the class of microRNAs has been studied in great detail, functional understanding of the much larger heterogeneous group of long ncRNAs (lncRNAs) is limited. Recently, participation in epigenetic processes has emerged as a common denominator of many lncRNAs. Epigenetic processes here mean the storage of information as a code of covalent DNA and chromatin modifications that mainly encodes the gene expression state of genomic regions. A large fraction of lncRNAs has been found to associate with epigenetic modifiers. Knockdown of such lncRNAs has led to loss of epigenetic silencing of specific regions, indicating that lncRNAs guide ubiquitously present modifying complexes to the site of action in the genome.
Epigenetic processes enable passing on adaptations cells have made in response to external stimuli to their offspring, i.e. provide an important link between genome and environment. Epigenetic mechanisms are particularly important for differentiation processes where commitment to a particular lineage needs to be maintained also in the absence of initial stimuli.