Research

Research

We develop bioinformatics-based solutions to the problems arising when data derived from multiple Omics-technologies are combined into larger datasets for integrative analysis. We have a strong background in all relevant steps starting from experimental design, the molecular biology behind sample and library preparation for a wide variety of experimental approaches as well as the bioinformatics and systems biology approaches important for the faithful and reproducible analysis of such complex data sets. The goal is to derive new and testable hypotheses that can be experimentally validated by biomedical scientists. We thereby anticipate to push forward the scientific endeavours aiming at a better understanding of the regulatory principles in place in our bodies’ cells. Ultimately, this interplay between bioinformatics and biomedicine is likely to facilitate the identification of disease causing mechanisms, new markers and potential therapeutic targets.

Transcriptomics

Gene regulation, i.e. the expression of genes, is a tightly controlled processes, that controls timing, location and the specific amount of transcribed mRNAs. Ultimately, the exact regulation of gene expression determines the identity of specific cell types, which differs between different cell types or even between different states of the same cell type, e.g. in the case of cells reacting to external stimuli. Furthermore, cells may differ in their gene expression profiles based on their disease state and detailed knowledge about such differential gene expression profiles may be important in order to identify disease markers or to identify potential targets for therapeutic intervention. We apply different approaches for the measurement of transcriptomes, with RNA-seq being the workhorse application in the field. Alternative methods involve targeted purification of specific RNA-species, RNA from different sub-cellular compartments or the measurement of freshly synthesized RNA by methods relying on metabolic labelling.

Epigenomics

The process of gene regulation is complex and involves multiple regulatory mechanisms including control mediated by the chromatin environment. All eukaryotes package their genome in form of chromatin, with the smallest building block of chromatin being the nucleosome. Further compaction is achieved by folding of chromatin fibers into higher-order structures. These structures are not static and several mechanisms have evolved that control the level of of chromatin compaction at specific sites. Exemplarily, cis-regulatory regions like promoters or enhancers are generally more accessible (less compacted) in active versus inactive states. Methods like ATAC-seq or DNAseI-seq allow sequencing-based genome-scale mapping of chromatin accessibility and provide valuable information about regulatory factors by studying the sequence context of differentially accessible chromatin regions.

Furthermore, histone proteins and the DNA itself can be modified by epigenetic modifications, which again can be experimentally identified by methods operating on genome-wide scale. Techniques like ChIP-seq and the more recently developed CUT&RUN or CUT&TAG can identify histone modifications or the binding of transcription factors based on NGS. Moreover, DNA methylation profiles can be obtained by methods like whole genome bisulphite sequencing (WGBS). Both modifications can influence the local chromatin structure and thereby control DNA-templated processes like transcription, replication or repair.

Combining several modalities studying chromatin structure and transcription can deliver interesting mechanistical insights into gene regulatory processes. The corresponding analyses are demanding and involve advanced bioinformatic approaches.