Computational RNA Biology
The precise spatial and temporal regulation of gene expression is essential for cellular function. A substantial portion of this regulation happens at the posttranscriptional level, at which a multitude of RNA-binding proteins (RBPs) control the structure and function of each transcript within the cell. By ensuring that diverse proteins are made at the right time and place, the posttranscriptional regulatory network plays a major role in human development and tissue identity, and its disruption is the underlying cause of numerous genetic disorders, with a particular prevalence for neurodegenerative diseases. Understanding the molecular mechanisms of posttranscriptional regulation, the responsible regulators and the associated defects is therefore of great importance.
Figure 1: The complex life of a eukaryotic mRNA. A plethora of RNA-binding proteins (RBPs) guide the mRNA through multiple nuclear and cytoplasmic processing steps, which ultimately determine its fate and function in the cell. Our group develops and applies new computational approaches to tackle this complex posttranscriptional regulatory network from a systemic perspective.
Our group uses computational methods to study the posttranscriptional regulatory system on a genomic scale. In particular, we aim to (i) characterise the molecular function of central regulatory RBPs, (ii) describe the underlying principles of critical regulatory decisions, and (iii) examine the contribution of erroneous transcript processing to human aging and disease. A main pillar of our work is the computational integration and biological interpretation of genome-wide datasets on RBP function and RNA processing events, including RBP binding maps, transcriptional profiles and translational activity measurements, with a particular interest in clinical RNA-seq data. To achieve this, we aim to develop new analytical approaches and computational tools that can be applied to answer a wide range of different questions in posttranscriptional regulation.