Initially, the research was mainly focused on studies of how mutations can disrupt the splicing regulatory mechanisms and cause disease. We have characterized numerous splicing regulatory elements and their binding proteins by using splicing reporter mini genes, expression systems for splicing regulatory factors and in vitro techniques.
In recent years, our laboratory has focused intensely on development of techniques for Next Generation Sequencing (NGS) of RNA, development of data-analysis pipelines, as well as global mapping and characterization of in vivo binding sites for splicing regulatory factors using iCLIP and eCLIP techniques.
We have now taken our projects to a new level, where we use global analysis of mRNA splicing in patient cells and cell lines, and global identification of binding motifs for splicing regulatory proteins in manipulated cells. This allows us to answer questions of a more general nature. One of our overall goals is the deciphering of the “splicing code”.
We employ RNA-affinity purification techniques and Surface Plasmon Resonance (SPR) based binding assays to identify and characterize binding of splicing regulatory proteins. Recently we have developed methods for modulation of splicing using splice shifting oligonucleotides (SSOs) to modulate splicing and to target disease-associated splicing regulatory elements aiming at development of new individualized therapies for inherited diseases as well as cancer.
Very recently we have initiated several projects studying splicing by the use of bioinformatics, including employing the supercomputer at SDU, Abacus 2.0, to use neural networks to analyze protein binding sites.
Our research is funded by grants from the National Danish Research Councils (FNU and FSS) and foundations such as Novo Nordisk Fonden and Lundbeck Fonden.
Head of research: Professor, PhD Brage Storstein Andresen
Researchers and research group: Brage Storstein Andresen Lab